Generic placeholder image

Current Topics in Medicinal Chemistry


ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Review Article

Unfolded Protein Response as a Therapeutic Target in Cardiovascular Disease

Author(s): Guangyu Zhang, Xiaoding Wang, Thomas G. Gillette, Yingfeng Deng and Zhao V. Wang*

Volume 19, Issue 21, 2019

Page: [1902 - 1917] Pages: 16

DOI: 10.2174/1568026619666190521093049

Price: $65


Cardiovascular disease is the leading cause of death worldwide. Despite overwhelming socioeconomic impact and mounting clinical needs, our understanding of the underlying pathophysiology remains incomplete. Multiple forms of cardiovascular disease involve an acute or chronic disturbance in cardiac myocytes, which may lead to potent activation of the Unfolded Protein Response (UPR), a cellular adaptive reaction to accommodate protein-folding stress. Accumulation of unfolded or misfolded proteins in the Endoplasmic Reticulum (ER) elicits three signaling branches of the UPR, which otherwise remain quiescent. This ER stress response then transiently suppresses global protein translation, augments production of protein-folding chaperones, and enhances ER-associated protein degradation, with an aim to restore cellular homeostasis. Ample evidence has established that the UPR is strongly induced in heart disease. Recently, the mechanisms of action and multiple pharmacological means to favorably modulate the UPR are emerging to curb the initiation and progression of cardiovascular disease. Here, we review the current understanding of the UPR in cardiovascular disease and discuss existing therapeutic explorations and future directions.

Keywords: Unfolded protein response, endoplasmic reticulum, GRP78, PERK, IRE1, ATF6, XBP1s, cardiovascular disease, pathological cardiac remodeling, ischemic heart disease.

Graphical Abstract
Benjamin, E.J.; Virani, S.S.; Callaway, C.W.; Chamberlain, A.M.; Chang, A.R.; Cheng, S.; Chiuve, S.E.; Cushman, M.; Delling, F.N.; Deo, R.; de Ferranti, S.D.; Ferguson, J.F.; Fornage, M.; Gillespie, C.; Isasi, C.R.; Jiménez, M.C.; Jordan, L.C.; Judd, S.E.; Lackland, D.; Lichtman, J.H.; Lisabeth, L.; Liu, S.; Longenecker, C.T.; Lutsey, P.L.; Mackey, J.S.; Matchar, D.B.; Matsushita, K.; Mussolino, M.E.; Nasir, K.; O’Flaherty, M.; Palaniappan, L.P.; Pandey, A.; Pandey, D.K.; Reeves, M.J.; Ritchey, M.D.; Rodriguez, C.J.; Roth, G.A.; Rosamond, W.D.; Sampson, U.K.A.; Satou, G.M.; Shah, S.H.; Spartano, N.L.; Tirschwell, D.L.; Tsao, C.W.; Voeks, J.H.; Willey, J.Z.; Wilkins, J.T.; Wu, J.H.; Alger, H.M.; Wong, S.S.; Muntner, P. Heart disease and stroke statistics-2018 update: A report from the american heart association. Circulation, 2018, 137(12), e67-e492.
[] [PMID: 29386200]
Arrieta, A.; Blackwood, E.A.; Glembotski, C.C. ER Protein quality control and the unfolded protein response in the heart. Curr. Top. Microbiol. Immunol., 2018, 414, 193-213.
[] [PMID: 29026925]
Ron, D.; Walter, P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat. Rev. Mol. Cell Biol., 2007, 8(7), 519-529.
[] [PMID: 17565364]
Groenendyk, J.; Sreenivasaiah, P.K.; Kim, D.H.; Agellon, L.B.; Michalak, M. Biology of endoplasmic reticulum stress in the heart. Circ. Res., 2010, 107(10), 1185-1197.
[] [PMID: 21071716]
Schröder, M.; Kaufman, R.J. The mammalian unfolded protein response. Annu. Rev. Biochem., 2005, 74, 739-789.
[] [PMID: 15952902]
Lee, A.S. The glucose-regulated proteins: Stress induction and clinical applications. Trends Biochem. Sci., 2001, 26(8), 504-510.
[] [PMID: 11504627]
Groenendyk, J.; Sreenivasaiah, P.K.; Kim, D.H.; Agellon, L.B.; Michalak, M. Biology of endoplasmic reticulum stress in the heart. Circ. Res., 2010, 107(10), 1185-1197.
[] [PMID: 21071716]
Walter, P.; Ron, D. The unfolded protein response: from stress pathway to homeostatic regulation. Science, 2011, 334(6059), 1081-1086.
[] [PMID: 22116877]
Hetz, C.; Martinon, F.; Rodriguez, D.; Glimcher, L.H. The unfolded protein response: Integrating stress signals through the stress sensor IRE1α. Physiol. Rev., 2011, 91(4), 1219-1243.
[] [PMID: 22013210]
Yoshida, H.; Matsui, T.; Yamamoto, A.; Okada, T.; Mori, K. XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell, 2001, 107(7), 881-891.
[] [PMID: 11779464]
Glembotski, C.C. Roles for ATF6 and the sarco/endoplasmic reticulum protein quality control system in the heart. J. Mol. Cell. Cardiol., 2014, 71, 11-15.
[] [PMID: 24140798]
Lee, A.H.; Scapa, E.F.; Cohen, D.E.; Glimcher, L.H. Regulation of hepatic lipogenesis by the transcription factor XBP1. Science, 2008, 320(5882), 1492-1496.
[] [PMID: 18556558]
Glimcher, L.H. XBP1: The last two decades. Ann. Rheum. Dis., 2010, 69(Suppl. 1), i67-i71.
[] [PMID: 19995749]
Wang, S.; Kaufman, R.J. The impact of the unfolded protein response on human disease. J. Cell Biol., 2012, 197(7), 857-867.
[] [PMID: 22733998]
Jin, J.K.; Blackwood, E.A.; Azizi, K.; Thuerauf, D.J.; Fahem, A.G.; Hofmann, C.; Kaufman, R.J.; Doroudgar, S.; Glembotski, C.C. ATF6 decreases myocardial ischemia/reperfusion damage and links ER stress and oxidative stress signaling pathways in the heart. Circ. Res., 2017, 120(5), 862-875.
[] [PMID: 27932512]
Blackwood, E.A.; Azizi, K.; Thuerauf, D.J.; Paxman, R.J.; Plate, L.; Kelly, J.W.; Wiseman, R.L.; Glembotski, C.C. Pharmacologic ATF6 activation confers global protection in widespread disease models by reprograming cellular proteostasis. Nat. Commun., 2019, 10(1), 187.
[] [PMID: 30643122]
Tabas, I.; Ron, D. Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat. Cell Biol., 2011, 13(3), 184-190.
[] [PMID: 21364565]
Ferri, K.F.; Kroemer, G. Organelle-specific initiation of cell death pathways. Nat. Cell Biol., 2001, 3(11), E255-E263.
[] [PMID: 11715037]
Kim, D.Y.; Kim, H.R.; Kim, K.K.; Park, J.W.; Lee, B.J. NELL2 function in the protection of cells against endoplasmic reticulum stress. Mol. Cells, 2015, 38(2), 145-150.
[] [PMID: 25537860]
Thuerauf, D.J.; Marcinko, M.; Gude, N.; Rubio, M.; Sussman, M.A.; Glembotski, C.C. Activation of the unfolded protein response in infarcted mouse heart and hypoxic cultured cardiac myocytes. Circ. Res., 2006, 99(3), 275-282.
[] [PMID: 16794188]
Okada, K.; Minamino, T.; Tsukamoto, Y.; Liao, Y.; Tsukamoto, O.; Takashima, S.; Hirata, A.; Fujita, M.; Nagamachi, Y.; Nakatani, T.; Yutani, C.; Ozawa, K.; Ogawa, S.; Tomoike, H.; Hori, M.; Kitakaze, M. Prolonged endoplasmic reticulum stress in hypertrophic and failing heart after aortic constriction: possible contribution of endoplasmic reticulum stress to cardiac myocyte apoptosis. Circulation, 2004, 110(6), 705-712.
[] [PMID: 15289376]
Hamada, H.; Suzuki, M.; Yuasa, S.; Mimura, N.; Shinozuka, N.; Takada, Y.; Suzuki, M.; Nishino, T.; Nakaya, H.; Koseki, H.; Aoe, T. Dilated cardiomyopathy caused by aberrant endoplasmic reticulum quality control in mutant KDEL receptor transgenic mice. Mol. Cell. Biol., 2004, 24(18), 8007-8017.
[] [PMID: 15340063]
Gargalovic, P.S.; Gharavi, N.M.; Clark, M.J.; Pagnon, J.; Yang, W.P.; He, A.; Truong, A.; Baruch-Oren, T.; Berliner, J.A.; Kirchgessner, T.G.; Lusis, A.J. The unfolded protein response is an important regulator of inflammatory genes in endothelial cells. Arterioscler. Thromb. Vasc. Biol., 2006, 26(11), 2490-2496.
[] [PMID: 16931790]
Tabas, I. The role of endoplasmic reticulum stress in the progression of atherosclerosis. Circ. Res., 2010, 107(7), 839-850.
[] [PMID: 20884885]
Li, R.J.; He, K.L.; Li, X.; Wang, L.L.; Liu, C.L.; He, Y.Y. Salubrinal protects cardiomyocytes against apoptosis in a rat myocardial infarction model via suppressing the dephosphorylation of eukaryotic translation initiation factor 2α. Mol. Med. Rep., 2015, 12(1), 1043-1049.
[] [PMID: 25816071]
Korennykh, A.V.; Egea, P.F.; Korostelev, A.A.; Finer-Moore, J.; Zhang, C.; Shokat, K.M.; Stroud, R.M.; Walter, P. The unfolded protein response signals through high-order assembly of Ire1. Nature, 2009, 457(7230), 687-693.
[] [PMID: 19079236]
Chu, T.F.; Rupnick, M.A.; Kerkela, R.; Dallabrida, S.M.; Zurakowski, D.; Nguyen, L.; Woulfe, K.; Pravda, E.; Cassiola, F.; Desai, J.; George, S.; Morgan, J.A.; Harris, D.M.; Ismail, N.S.; Chen, J.H.; Schoen, F.J.; Van den Abbeele, A.D.; Demetri, G.D.; Force, T.; Chen, M.H. Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib. Lancet, 2007, 370(9604), 2011-2019.
[] [PMID: 18083403]
Perlmutter, D.H. Chemical chaperones: A pharmacological strategy for disorders of protein folding and trafficking. Pediatr. Res., 2002, 52(6), 832-836.
[] [PMID: 12438657]
Park, C.S.; Cha, H.; Kwon, E.J.; Sreenivasaiah, P.K.; Kim, D.H. The chemical chaperone 4-phenylbutyric acid attenuates pressure-overload cardiac hypertrophy by alleviating endoplasmic reticulum stress. Biochem. Biophys. Res. Commun., 2012, 421(3), 578-584.
[] [PMID: 22525677]
Ayala, P.; Montenegro, J.; Vivar, R.; Letelier, A.; Urroz, P.A.; Copaja, M.; Pivet, D.; Humeres, C.; Troncoso, R.; Vicencio, J.M.; Lavandero, S.; Díaz-Araya, G. Attenuation of endoplasmic reticulum stress using the chemical chaperone 4-phenylbutyric acid prevents cardiac fibrosis induced by isoproterenol. Exp. Mol. Pathol., 2012, 92(1), 97-104.
[] [PMID: 22101259]
Guo, R.; Ma, H.; Gao, F.; Zhong, L.; Ren, J. Metallothionein alleviates oxidative stress-induced endoplasmic reticulum stress and myocardial dysfunction. J. Mol. Cell. Cardiol., 2009, 47(2), 228-237.
[] [PMID: 19344729]
Cornejo, V.H.; Pihán, P.; Vidal, R.L.; Hetz, C. Role of the unfolded protein response in organ physiology: Lessons from mouse models. IUBMB Life, 2013, 65(12), 962-975.
[] [PMID: 24227223]
Masaki, T.; Yoshida, M.; Noguchi, S. Targeted disruption of CRE-binding factor TREB5 gene leads to cellular necrosis in cardiac myocytes at the embryonic stage. Biochem. Biophys. Res. Commun., 1999, 261(2), 350-356.
[] [PMID: 10425189]
Chen, Y.; Brandizzi, F. IRE1: ER stress sensor and cell fate executor. Trends Cell Biol., 2013, 23(11), 547-555.
[] [PMID: 23880584]
Gao, Y.; Sartori, D.J.; Li, C.; Yu, Q.C.; Kushner, J.A.; Simon, M.C.; Diehl, J.A. PERK is required in the adult pancreas and is essential for maintenance of glucose homeostasis. Mol. Cell. Biol., 2012, 32(24), 5129-5139.
[] [PMID: 23071091]
Chen, X.; Zhang, F.; Gong, Q.; Cui, A.; Zhuo, S.; Hu, Z.; Han, Y.; Gao, J.; Sun, Y.; Liu, Z.; Yang, Z.; Le, Y.; Gao, X.; Dong, L.Q.; Gao, X.; Li, Y. Hepatic ATF6 increases fatty acid oxidation to attenuate hepatic steatosis in mice through peroxisome proliferator-activated receptor α. Diabetes, 2016, 65(7), 1904-1915.
[] [PMID: 27207533]
Little, E.; Ramakrishnan, M.; Roy, B.; Gazit, G.; Lee, A.S. The glucose-regulated proteins (GRP78 and GRP94): Functions, gene regulation, and applications. Crit. Rev. Eukaryot. Gene Expr., 1994, 4(1), 1-18.
[] [PMID: 7987045]
Koumenis, C. ER stress, hypoxia tolerance and tumor progression. Curr. Mol. Med., 2006, 6(1), 55-69.
[] [PMID: 16472113]
Kao, C.; Chandna, R.; Ghode, A.; Dsouza, C.; Chen, M.; Larsson, A.; Lim, S.H.; Wang, M.; Cao, Z.; Zhu, Y.; Anand, G.S.; Ge, R. Proapoptotic cyclic peptide BC71 targets cell-surface GRP78 and functions as an anticancer therapeutic in mice. EBioMedicine, 2018, 33, 22-32.
[] [PMID: 29907328]
Araujo, N.; Hebbar, N.; Rangnekar, V.M. GRP78 is a targetable receptor on cancer and stromal cells. EBioMedicine, 2018, 33, 2-3.
[] [PMID: 29997052]
Zhang, Y.; Liu, R.; Ni, M.; Gill, P.; Lee, A.S. Cell surface relocalization of the endoplasmic reticulum chaperone and unfolded protein response regulator GRP78/BiP. J. Biol. Chem., 2010, 285(20), 15065-15075.
[] [PMID: 20208072]
Birukova, A.A.; Singleton, P.A.; Gawlak, G.; Tian, X.; Mirzapoiazova, T.; Mambetsariev, B.; Dubrovskyi, O.; Oskolkova, O.V.; Bochkov, V.N.; Birukov, K.G. GRP78 is a novel receptor initiating a vascular barrier protective response to oxidized phospholipids. Mol. Biol. Cell, 2014, 25(13), 2006-2016.
[] [PMID: 24829380]
Tsai, Y.L.; Ha, D.P.; Zhao, H.; Carlos, A.J.; Wei, S.; Pun, T.K.; Wu, K.; Zandi, E.; Kelly, K.; Lee, A.S. Endoplasmic reticulum stress activates SRC, relocating chaperones to the cell surface where GRP78/CD109 blocks TGF-β signaling. Proc. Natl. Acad. Sci. USA, 2018, 115(18), E4245-E4254.
[] [PMID: 29654145]
Misra, U.K.; Deedwania, R.; Pizzo, S.V. Binding of activated alpha2-macroglobulin to its cell surface receptor GRP78 in 1-LN prostate cancer cells regulates PAK-2-dependent activation of LIMK. J. Biol. Chem., 2005, 280(28), 26278-26286.
[] [PMID: 15908432]
Sokolowska, I.; Woods, A.G.; Gawinowicz, M.A.; Roy, U.; Darie, C.C. Identification of a potential tumor differentiation factor receptor candidate in prostate cancer cells. FEBS J., 2012, 279(14), 2579-2594.
[] [PMID: 22613557]
Ni, M.; Zhang, Y.; Lee, A.S. Beyond the endoplasmic reticulum: Atypical GRP78 in cell viability, signalling and therapeutic targeting. Biochem. J., 2011, 434(2), 181-188.
[] [PMID: 21309747]
Philippova, M.; Ivanov, D.; Joshi, M.B.; Kyriakakis, E.; Rupp, K.; Afonyushkin, T.; Bochkov, V.; Erne, P.; Resink, T.J. Identification of proteins associating with glycosylphosphatidylinositol- anchored T-cadherin on the surface of vascular endothelial cells: Role for Grp78/BiP in T-cadherin-dependent cell survival. Mol. Cell. Biol., 2008, 28(12), 4004-4017.
[] [PMID: 18411300]
Zhu, G.; Lee, A.S. Role of the unfolded protein response, GRP78 and GRP94 in organ homeostasis. J. Cell. Physiol., 2015, 230(7), 1413-1420.
[] [PMID: 25546813]
Luo, S.; Mao, C.; Lee, B.; Lee, A.S. GRP78/BiP is required for cell proliferation and protecting the inner cell mass from apoptosis during early mouse embryonic development. Mol. Cell. Biol., 2006, 26(15), 5688-5697.
[] [PMID: 16847323]
Zhu, G.; Ye, R.; Jung, D.Y.; Barron, E.; Friedline, R.H.; Benoit, V.M.; Hinton, D.R.; Kim, J.K.; Lee, A.S. GRP78 plays an essential role in adipogenesis and postnatal growth in mice. FASEB J., 2013, 27(3), 955-964.
[] [PMID: 23180827]
Flodby, P.; Li, C.; Liu, Y.; Wang, H.; Marconett, C.N.; Laird-Offringa, I.A.; Minoo, P.; Lee, A.S.; Zhou, B. The 78-kD Glucose-regulated protein regulates endoplasmic reticulum homeostasis and distal epithelial cell survival during lung development. Am. J. Respir. Cell Mol. Biol., 2016, 55(1), 135-149.
[] [PMID: 26816051]
Wang, X.; Bi, X.; Zhang, G.; Deng, Y.; Luo, X.; Xu, L.; Scherer, P.E.; Ferdous, A.; Fu, G.; Gillette, T.G.; Lee, A.S.; Jiang, X.; Wang, Z.V. Glucose-regulated protein 78 is essential for cardiac myocyte survival. Cell Death Differ., 2018, 25(12), 2181-2194.
[] [PMID: 29666470]
Thuerauf, D.J.; Marcinko, M.; Gude, N.; Rubio, M.; Sussman, M.A.; Glembotski, C.C. Activation of the unfolded protein response in infarcted mouse heart and hypoxic cultured cardiac myocytes. Circ. Res., 2006, 99(3), 275-282.
[] [PMID: 16794188]
Wang, Z.V.; Deng, Y.; Gao, N.; Pedrozo, Z.; Li, D.L.; Morales, C.R.; Criollo, A.; Luo, X.; Tan, W.; Jiang, N.; Lehrman, M.A.; Rothermel, B.A.; Lee, A.H.; Lavandero, S.; Mammen, P.P.A.; Ferdous, A.; Gillette, T.G.; Scherer, P.E.; Hill, J.A. Spliced X-box binding protein 1 couples the unfolded protein response to hexosamine biosynthetic pathway. Cell, 2014, 156(6), 1179-1192.
[] [PMID: 24630721]
Bi, X.; Zhang, G.; Wang, X.; Nguyen, C.; May, H.I.; Li, X.; Al-Hashimi, A.A.; Austin, R.C.; Gillette, T.G.; Fu, G.; Wang, Z.V.; Hill, J.A. Endoplasmic reticulum chaperone GRP78 protects heart from ischemia/reperfusion injury through Akt activation. Circ. Res., 2018, 122(11), 1545-1554.
[] [PMID: 29669712]
Zhang, G.; Wang, X.; Bi, X.; Li, C.; Deng, Y.; Al-Hashimi, A.A.; Luo, X.; Gillette, T.G.; Austin, R.C.; Wang, Y.; Wang, Z.V. GRP78 (Glucose-regulated protein of 78 kDa) promotes cardiomyocyte growth through activation of GATA4 (GATA-binding protein 4). Hypertension, 2019, 73(2), 390-398.
[] [PMID: 30580686]
Gao, G.; Xie, A.; Zhang, J.; Herman, A.M.; Jeong, E.M.; Gu, L.; Liu, M.; Yang, K.C.; Kamp, T.J.; Dudley, S.C. Unfolded protein response regulates cardiac sodium current in systolic human heart failure. Circ Arrhythm Electrophysiol, 2013, 6(5), 1018-1024.
[] [PMID: 24036084]
Ross, C.A.; Poirier, M.A. Protein aggregation and neurodegenerative disease. Nat. Med., 2004, 10(Suppl.), S10-S17.
Selkoe, D.J. Folding proteins in fatal ways. Nature, 2003, 426(6968), 900-904.
[] [PMID: 14685251]
Taylor, J.P.; Hardy, J.; Fischbeck, K.H. Toxic proteins in neurodegenerative disease. Science, 2002, 296(5575), 1991-1995.
[] [PMID: 12065827]
Kopito, R.R.; Ron, D. Conformational disease. Nat. Cell Biol., 2000, 2(11), E207-E209.
[] [PMID: 11056553]
Kudo, T.; Kanemoto, S.; Hara, H.; Morimoto, N.; Morihara, T.; Kimura, R.; Tabira, T.; Imaizumi, K.; Takeda, M. A molecular chaperone inducer protects neurons from ER stress. Cell Death Differ., 2008, 15(2), 364-375.
[] [PMID: 18049481]
Nakanishi, T.; Shimazawa, M.; Sugitani, S.; Kudo, T.; Imai, S.; Inokuchi, Y.; Tsuruma, K.; Hara, H. Role of endoplasmic reticulum stress in light-induced photoreceptor degeneration in mice. J. Neurochem., 2013, 125(1), 111-124.
[] [PMID: 23216380]
Shimazawa, M.; Inokuchi, Y.; Okuno, T.; Nakajima, Y.; Sakaguchi, G.; Kato, A.; Oku, H.; Sugiyama, T.; Kudo, T.; Ikeda, T.; Takeda, M.; Hara, H. Reduced retinal function in amyloid precursor protein-over-expressing transgenic mice via attenuating glutamate-N-methyl-d-aspartate receptor signaling. J. Neurochem., 2008, 107(1), 279-290.
[] [PMID: 18691390]
Oida, Y.; Hamanaka, J.; Hyakkoku, K.; Shimazawa, M.; Kudo, T.; Imaizumi, K.; Yasuda, T.; Hara, H. Post-treatment of a BiP inducer prevents cell death after middle cerebral artery occlusion in mice. Neurosci. Lett., 2010, 484(1), 43-46.
[] [PMID: 20709152]
Takano, K.; Tabata, Y.; Kitao, Y.; Murakami, R.; Suzuki, H.; Yamada, M.; Iinuma, M.; Yoneda, Y.; Ogawa, S.; Hori, O. Methoxyflavones protect cells against endoplasmic reticulum stress and neurotoxin. Am. J. Physiol. Cell Physiol., 2007, 292(1), C353-C361.
[] [PMID: 16971492]
Lee, A.S. Glucose-regulated proteins in cancer: Molecular mechanisms and therapeutic potential. Nat. Rev. Cancer, 2014, 14(4), 263-276.
[] [PMID: 24658275]
Wang, M.; Wey, S.; Zhang, Y.; Ye, R.; Lee, A.S. Role of the unfolded protein response regulator GRP78/BiP in development, cancer, and neurological disorders. Antioxid. Redox Signal., 2009, 11(9), 2307-2316.
[] [PMID: 19309259]
Casas, C. GRP78 at the centre of the stage in cancer and neuroprotection. Front. Neurosci., 2017, 11, 177.
[] [PMID: 28424579]
Bytzek, A.K.; Koellensperger, G.; Keppler, B.K.G.; Hartinger, C. Biodistribution of the novel anticancer drug sodium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] KP-1339/IT139 in nude BALB/c mice and implications on its mode of action. J. Inorg. Biochem., 2016, 160, 250-255.
[] [PMID: 26993078]
Burris, H.A.; Bakewell, S.; Bendell, J.C.; Infante, J.; Jones, S.F.; Spigel, D.R.; Weiss, G.J.; Ramanathan, R.K.; Ogden, A.; Von Hoff, D. Safety and activity of IT-139, a ruthenium-based compound, in patients with advanced solid tumours: a first-in-human, open-label, dose-escalation phase I study with expansion cohort. ESMO Open, 2017, 1(6)e000154
[] [PMID: 28848672]
Chang, S.W.; Lewis, A.R.; Prosser, K.E.; Thompson, J.R.; Gladkikh, M.; Bally, M.B.; Warren, J.J.; Walsby, C.J. CF3 derivatives of the anticancer Ru(III) complexes KP1019, NKP-1339, and their imidazole and pyridine analogues show enhanced lipophilicity, albumin interactions, and cytotoxicity. Inorg. Chem., 2016, 55(10), 4850-4863.
[] [PMID: 27143338]
Dömötör, O.; Hartinger, C.G.; Bytzek, A.K.; Kiss, T.; Keppler, B.K.; Enyedy, E.A. Characterization of the binding sites of the anticancer ruthenium(III) complexes KP1019 and KP1339 on human serum albumin via competition studies. J. Biol. Inorg. Chem., 2013, 18(1), 9-17.
[] [PMID: 23076343]
Schonhacker-Alte, B.; Baier, D.; Mohr, T.; Pirker, C.; Buck, A.; Hofmann, T.; Keppler, B.; Berger, W.; Heffeter, P. Update on NKP-1339/IT-139, a ruthenium-based GRP78 inhibitor in clinical development. Oncol. Res. Treat., 2018, 41, 47-48.
Lentz, F.; Drescher, A.; Lindauer, A.; Henke, M.; Hilger, R.A.; Hartinger, C.G.; Scheulen, M.E.; Dittrich, C.; Keppler, B.K.; Jaehde, U. Pharmacokinetics of a novel anticancer ruthenium complex (KP1019, FFC14A) in a phase I dose-escalation study. Anticancer Drugs, 2009, 20(2), 97-103.
[] [PMID: 19209025]
Cerezo, M.; Lehraiki, A.; Millet, A.; Rouaud, F.; Plaisant, M.; Jaune, E.; Botton, T.; Ronco, C.; Abbe, P.; Amdouni, H.; Passeron, T.; Hofman, V.; Mograbi, B.; Dabert-Gay, A.S.; Debayle, D.; Alcor, D.; Rabhi, N.; Annicotte, J.S.; Héliot, L.; Gonzalez-Pisfil, M.; Robert, C.; Moréra, S.; Vigouroux, A.; Gual, P.; Ali, M.M.U.; Bertolotto, C.; Hofman, P.; Ballotti, R.; Benhida, R.; Rocchi, S. compounds triggering ER stress exert anti-melanoma effects and overcome BRAF inhibitor resistance. Cancer Cell, 2016, 29(6), 805-819.
[] [PMID: 27238082]
Ronco, C.; Millet, A.; Plaisant, M.; Abbe, P.; Hamouda-Tekaya, N.; Rocchi, S.; Benhida, R. Structure activity relationship and optimization of N-(3-(2-aminothiazol-4-yl)aryl)benzenesulfonamides as anti-cancer compounds against sensitive and resistant cells. Bioorg. Med. Chem. Lett., 2017, 27(10), 2192-2196.
[] [PMID: 28372910]
Bhattacharjee, R.; Devi, A.; Mishra, S. Molecular docking and molecular dynamics studies reveal structural basis of inhibition and selectivity of inhibitors EGCG and OSU-03012 toward glucose regulated protein-78 (GRP78) overexpressed in glioblastoma. J. Mol. Model., 2015, 21(10), 272.
[] [PMID: 26419972]
Booth, L.; Cazanave, S.C.; Hamed, H.A.; Yacoub, A.; Ogretmen, B.; Chen, C.S.; Grant, S.; Dent, P. OSU-03012 suppresses GRP78/BiP expression that causes PERK-dependent increases in tumor cell killing. Cancer Biol. Ther., 2012, 13(4), 224-236.
[] [PMID: 22354011]
Park, M.A.; Yacoub, A.; Rahmani, M.; Zhang, G.; Hart, L.; Hagan, M.P.; Calderwood, S.K.; Sherman, M.Y.; Koumenis, C.; Spiegel, S.; Chen, C.S.; Graf, M.; Curiel, D.T.; Fisher, P.B.; Grant, S.; Dent, P. OSU-03012 stimulates PKR-like endoplasmic reticulum-dependent increases in 70-kDa heat shock protein expression, attenuating its lethal actions in transformed cells. Mol. Pharmacol., 2008, 73(4), 1168-1184.
[] [PMID: 18182481]
Park, H.R.; Ryoo, I.J.; Choo, S.J.; Hwang, J.H.; Kim, J.Y.; Cha, M.R.; Shin-Ya, K.; Yoo, I.D. Glucose-deprived HT-29 human colon carcinoma cells are sensitive to verrucosidin as a GRP78 down-regulator. Toxicology, 2007, 229(3), 253-261.
[] [PMID: 17161515]
Thomas, S.; Sharma, N.; Gonzalez, R.; Pao, P.W.; Hofman, F.M.; Chen, T.C.; Louie, S.G.; Pirrung, M.C.; Schönthal, A.H. Repositioning of Verrucosidin, a purported inhibitor of chaperone protein GRP78, as an inhibitor of mitochondrial electron transport chain complex I. PLoS One, 2013, 8(6)e65695
[] [PMID: 23755268]
Kim, J.Y.; Hwang, J.H.; Cha, M.R.; Yoon, M.Y.; Son, E.S.; Tomida, A.; Ko, B.; Song, S.W.; Shin-ya, K.; Hwang, Y.I.; Park, H.R. Arctigenin blocks the unfolded protein response and shows therapeutic antitumor activity. J. Cell. Physiol., 2010, 224(1), 33-40.
[] [PMID: 20232300]
Kato, K.; Gong, J.; Iwama, H.; Kitanaka, A.; Tani, J.; Miyoshi, H.; Nomura, K.; Mimura, S.; Kobayashi, M.; Aritomo, Y.; Kobara, H.; Mori, H.; Himoto, T.; Okano, K.; Suzuki, Y.; Murao, K.; Masaki, T. The antidiabetic drug metformin inhibits gastric cancer cell proliferation in vitro and in vivo. Mol. Cancer Ther., 2012, 11(3), 549-560.
[] [PMID: 22222629]
Yu, D.H.; Macdonald, J.; Liu, G.; Lee, A.S.; Ly, M.; Davis, T.; Ke, N.; Zhou, D.; Wong-Staal, F.; Li, Q.X. Pyrvinium targets the unfolded protein response to hypoglycemia and its anti-tumor activity is enhanced by combination therapy. PLoS One, 2008, 3(12)e3951
[] [PMID: 19079611]
Park, H.R.; Tomida, A.; Sato, S.; Tsukumo, Y.; Yun, J.; Yamori, T.; Hayakawa, Y.; Tsuruo, T.; Shin-ya, K. Effect on tumor cells of blocking survival response to glucose deprivation. J. Natl. Cancer Inst., 2004, 96(17), 1300-1310.
[] [PMID: 15339968]
Maddalo, D.; Neeb, A.; Jehle, K.; Schmitz, K.; Muhle-Goll, C.; Shatkina, L.; Walther, T.V.; Bruchmann, A.; Gopal, S.M.; Wenzel, W.; Ulrich, A.S.; Cato, A.C. A peptidic unconjugated GRP78/BiP ligand modulates the unfolded protein response and induces prostate cancer cell death. PLoS One, 2012, 7(10)e45690
[] [PMID: 23049684]
Cunningham, C.C.; Chada, S.; Merritt, J.A.; Tong, A.; Senzer, N.; Zhang, Y.; Mhashilkar, A.; Parker, K.; Vukelja, S.; Richards, D.; Hood, J.; Coffee, K.; Nemunaitis, J. Clinical and local biological effects of an intratumoral injection of mda-7 (IL24; INGN 241) in patients with advanced carcinoma: a phase I study. Mol. Ther., 2005, 11(1), 149-159.
[] [PMID: 15585416]
Gupta, P.; Walter, M.R.; Su, Z.Z.; Lebedeva, I.V.; Emdad, L.; Randolph, A.; Valerie, K.; Sarkar, D.; Fisher, P.B. BiP/GRP78 is an intracellular target for MDA-7/IL-24 induction of cancer-specific apoptosis. Cancer Res., 2006, 66(16), 8182-8191.
[] [PMID: 16912197]
Arap, M.A.; Lahdenranta, J.; Mintz, P.J.; Hajitou, A.; Sarkis, A.S.; Arap, W.; Pasqualini, R. Cell surface expression of the stress response chaperone GRP78 enables tumor targeting by circulating ligands. Cancer Cell, 2004, 6(3), 275-284.
[] [PMID: 15380518]
Yoneda, Y.; Steiniger, S.C.J.; Capková, K.; Mee, J.M.; Liu, Y.; Kaufmann, G.F.; Janda, K.D. A cell-penetrating peptidic GRP78 ligand for tumor cell-specific prodrug therapy. Bioorg. Med. Chem. Lett., 2008, 18(5), 1632-1636.
[] [PMID: 18243696]
Katanasaka, Y.; Ishii, T.; Asai, T.; Naitou, H.; Maeda, N.; Koizumi, F.; Miyagawa, S.; Ohashi, N.; Oku, N. Cancer antineovascular therapy with liposome drug delivery systems targeted to BiP/GRP78. Int. J. Cancer, 2010, 127(11), 2685-2698.
[] [PMID: 20178102]
Passarella, R.J.; Spratt, D.E.; van der Ende, A.E.; Phillips, J.G.; Wu, H.; Sathiyakumar, V.; Zhou, L.; Hallahan, D.E.; Harth, E.; Diaz, R. Targeted nanoparticles that deliver a sustained, specific release of Paclitaxel to irradiated tumors. Cancer Res., 2010, 70(11), 4550-4559.
[] [PMID: 20484031]
Saito, A.; Ochiai, K.; Kondo, S.; Tsumagari, K.; Murakami, T.; Cavener, D.R.; Imaizumi, K. Endoplasmic reticulum stress response mediated by the PERK-eIF2(alpha)-ATF4 pathway is involved in osteoblast differentiation induced by BMP2. J. Biol. Chem., 2011, 286(6), 4809-4818.
[] [PMID: 21135100]
Cui, W.; Li, J.; Ron, D.; Sha, B. The structure of the PERK kinase domain suggests the mechanism for its activation. Acta Crystallogr. D Biol. Crystallogr., 2011, 67(Pt 5), 423-428.
[] [PMID: 21543844]
Liu, X.; Kwak, D.; Lu, Z.; Xu, X.; Fassett, J.; Wang, H.; Wei, Y.; Cavener, D.R.; Hu, X.; Hall, J.; Bache, R.J.; Chen, Y. Endoplasmic reticulum stress sensor protein kinase R-like endoplasmic reticulum kinase (PERK) protects against pressure overload-induced heart failure and lung remodeling. Hypertension, 2014, 64(4), 738-744.
[] [PMID: 24958502]
Liu, Z.W.; Zhu, H.T.; Chen, K.L.; Dong, X.; Wei, J.; Qiu, C.; Xue, J.H. Protein kinase RNA-like endoplasmic reticulum kinase (PERK) signaling pathway plays a major role in reactive oxygen species (ROS)-mediated endoplasmic reticulum stress-induced apoptosis in diabetic cardiomyopathy. Cardiovasc. Diabetol., 2013, 12, 158.
[] [PMID: 24180212]
McAlpine, C.S.; Werstuck, G.H. Protein kinase R-like endoplasmic reticulum kinase and glycogen synthase kinase-3α/β regulate foam cell formation. J. Lipid Res., 2014, 55(11), 2320-2333.
[] [PMID: 25183803]
Axten, J.M. Protein kinase R(PKR)-like endoplasmic reticulum kinase (PERK) inhibitors: a patent review (2010-2015). Expert Opin. Ther. Pat., 2017, 27(1), 37-48.
[] [PMID: 27646439]
Han, J.; Back, S.H.; Hur, J.; Lin, Y.H.; Gildersleeve, R.; Shan, J.; Yuan, C.L.; Krokowski, D.; Wang, S.; Hatzoglou, M.; Kilberg, M.S.; Sartor, M.A.; Kaufman, R.J. ER-stress-induced transcriptional regulation increases protein synthesis leading to cell death. Nat. Cell Biol., 2013, 15(5), 481-490.
[] [PMID: 23624402]
Lu, P.D.; Jousse, C.; Marciniak, S.J.; Zhang, Y.; Novoa, I.; Scheuner, D.; Kaufman, R.J.; Ron, D.; Harding, H.P. Cytoprotection by pre-emptive conditional phosphorylation of translation initiation factor 2. EMBO J., 2004, 23(1), 169-179.
[] [PMID: 14713949]
Ranganathan, A.C.; Ojha, S.; Kourtidis, A.; Conklin, D.S.; Aguirre-Ghiso, J.A. Dual function of pancreatic endoplasmic reticulum kinase in tumor cell growth arrest and survival. Cancer Res., 2008, 68(9), 3260-3268.
[] [PMID: 18451152]
Wang, L.; Popko, B.; Tixier, E.; Roos, R.P. Guanabenz, which enhances the unfolded protein response, ameliorates mutant SOD1-induced amyotrophic lateral sclerosis. Neurobiol. Dis., 2014, 71, 317-324.
[] [PMID: 25134731]
Way, S.W.; Popko, B. Harnessing the integrated stress response for the treatment of multiple sclerosis. Lancet Neurol., 2016, 15(4), 434-443.
[] [PMID: 26873788]
Smith, A.L.; Andrews, K.L.; Beckmann, H.; Bellon, S.F.; Beltran, P.J.; Booker, S.; Chen, H.; Chung, Y.A.; D’Angelo, N.D.; Dao, J.; Dellamaggiore, K.R.; Jaeckel, P.; Kendall, R.; Labitzke, K.; Long, A.M.; Materna-Reichelt, S.; Mitchell, P.; Norman, M.H.; Powers, D.; Rose, M.; Shaffer, P.L.; Wu, M.M.; Lipford, J.R. Discovery of 1H-pyrazol-3(2H)-ones as potent and selective inhibitors of protein kinase R-like endoplasmic reticulum kinase (PERK). J. Med. Chem., 2015, 58(3), 1426-1441.
[] [PMID: 25587754]
Wang, H.; Blais, J.; Ron, D.; Cardozo, T. Structural determinants of PERK inhibitor potency and selectivity. Chem. Biol. Drug Des., 2010, 76(6), 480-495.
[] [PMID: 21070610]
Pytel, D.; Majsterek, I.; Diehl, J.A. Tumor progression and the different faces of the PERK kinase. Oncogene, 2016, 35(10), 1207-1215.
[] [PMID: 26028033]
Moreno, J.A.; Halliday, M.; Molloy, C.; Radford, H.; Verity, N.; Axten, J.M.; Ortori, C.A.; Willis, A.E.; Fischer, P.M.; Barrett, D.A.; Mallucci, G.R. Oral treatment targeting the unfolded protein response prevents neurodegeneration and clinical disease in prion-infected mice. Sci. Transl. Med., 2013, 5(206)206ra138
[] [PMID: 24107777]
Nijholt, D.A.T.; van Haastert, E.S.; Rozemuller, A.J.M.; Scheper, W.; Hoozemans, J.J.M. The unfolded protein response is associated with early tau pathology in the hippocampus of tauopathies. J. Pathol., 2012, 226(5), 693-702.
[] [PMID: 22102449]
Shen, J.; Chen, X.; Hendershot, L.; Prywes, R. ER stress regulation of ATF6 localization by dissociation of BiP/GRP78 binding and unmasking of Golgi localization signals. Dev. Cell, 2002, 3(1), 99-111.
[] [PMID: 12110171]
Doroudgar, S.; Thuerauf, D.J.; Marcinko, M.M.; Glembotski, C.C. Simulated .ischemia activates the ATF6 branch of the endoplasmic reticulum stress response in cultured cardiac myocytes. Circ.n Res., 2008, 103(5), E69-E70.
Doroudgar, S.; Thuerauf, D.J.; Marcinko, M.C.; Belmont, P.J.; Glembotski, C.C. Ischemia activates the ATF6 branch of the endoplasmic reticulum stress response. J. Biol. Chem., 2009, 284(43), 29735-29745.
[] [PMID: 19622751]
Martindale, J.J.; Fernandez, R.; Thuerauf, D.; Whittaker, R.; Gude, N.; Sussman, M.A.; Glembotski, C.C. Endoplasmic reticulum stress gene induction and protection from ischemia/reperfusion injury in the hearts of transgenic mice with a tamoxifen-regulated form of ATF6. Circ. Res., 2006, 98(9), 1186-1193.
[] [PMID: 16601230]
Blackwood, E.A.; Hofmann, C.; Santo Domingo, M.; Bilal, A.S.; Sarakki, A.; Stauffer, W.; Arrieta, A.; Thuerauf, D.J.; Kolkhorst, F.W.; Müller, O.J.; Jakobi, T.; Dieterich, C.; Katus, H.A.; Doroudgar, S.; Glembotski, C.C. ATF6 regulates cardiac hypertrophy by transcriptional induction of the mTORC1 activator, Rheb. Circ. Res., 2019, 124(1), 79-93.
[] [PMID: 30582446]
Liu, Z.; Zhang, Y.; Tang, Z.; Xu, J.; Ma, M.; Pan, S.; Qiu, C.; Guan, G.; Wang, J. Matrine attenuates cardiac fibrosis by affecting ATF6 signaling pathway in diabetic cardiomyopathy. Eur. J. Pharmacol., 2017, 804, 21-30.
[] [PMID: 28373137]
Paxman, R.; Plate, L.; Blackwood, E.A.; Glembotski, C.; Powers, E.T.; Wiseman, R.L.; Kelly, J.W. Pharmacologic ATF6 activating compounds are metabolically activated to selectively modify endoplasmic reticulum proteins. eLife, 2018, 7, 7.
[] [PMID: 30084354]
Tam, A.B.; Roberts, L.S.; Chandra, V.; Rivera, I.G.; Nomura, D.K.; Forbes, D.J.; Niwa, M. The UPR activator ATF6 responds to proteotoxic and lipotoxic stress by distinct mechanisms. Dev. Cell, 2018, 46(3), 327-343.e7.
[] [PMID: 30086303]
Gallagher, C.M.; Garri, C.; Cain, E.L.; Ang, K.K.H.; Wilson, C.G.; Chen, S.; Hearn, B.R.; Jaishankar, P.; Aranda-Diaz, A.; Arkin, M.R.; Renslo, A.R.; Walter, P. Ceapins are a new class of unfolded protein response inhibitors, selectively targeting the ATF6 alpha branch. eLife, 2016, 5e11878
[] [PMID: 27435960]
Lebeau, P.; Byun, J.H.; Yousof, T.; Austin, R.C. Pharmacologic inhibition of S1P attenuates ATF6 expression, causes ER stress and contributes to apoptotic cell death. Toxicol. Appl. Pharmacol., 2018, 349, 1-7.
[] [PMID: 29689241]
Calfon, M.; Zeng, H.; Urano, F.; Till, J.H.; Hubbard, S.R.; Harding, H.P.; Clark, S.G.; Ron, D. IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature, 2002, 415(6867), 92-96.
[] [PMID: 11780124]
Wang, Z.V.; Hill, J.A. Protein quality control and metabolism: bidirectional control in the heart. Cell Metab., 2015, 21(2), 215-226.
[] [PMID: 25651176]
Steiger, D.; Yokota, T.; Li, J.; Ren, S.; Minamisawa, S.; Wang, Y. The serine/threonine-protein kinase/endoribonuclease IRE1α protects the heart against pressure overload-induced heart failure. J. Biol. Chem., 2018, 293(25), 9652-9661.
[] [PMID: 29769316]
Yao, S.; Miao, C.; Tian, H.; Sang, H.; Yang, N.; Jiao, P.; Han, J.; Zong, C.; Qin, S. Endoplasmic reticulum stress promotes macrophage-derived foam cell formation by up-regulating cluster of differentiation 36 (CD36) expression. J. Biol. Chem., 2014, 289(7), 4032-4042.
[] [PMID: 24366867]
Wang, X.; Xu, L.; Gillette, T.G.; Jiang, X.; Wang, Z.V. The unfolded protein response in ischemic heart disease. J. Mol. Cell. Cardiol., 2018, 117, 19-25.
[] [PMID: 29470977]
Duan, Q.; Ni, L.; Wang, P.; Chen, C.; Yang, L.; Ma, B.; Gong, W.; Cai, Z.; Zou, M.H.; Wang, D.W. Deregulation of XBP1 expression contributes to myocardial vascular endothelial growth factor-A expression and angiogenesis during cardiac hypertrophy in vivo. Aging Cell, 2016, 15(4), 625-633.
[] [PMID: 27133203]
Vincenz, L.; Hartl, F.U. Sugarcoating ER stress. Cell, 2014, 156(6), 1125-1127.
[] [PMID: 24630714]
Glembotski, C.C. Finding the missing link between the unfolded protein response and O-GlcNAcylation in the heart. Circ. Res., 2014, 115(6), 546-548.
[] [PMID: 25170091]
Zeng, L.; Zampetaki, A.; Margariti, A.; Pepe, A.E.; Alam, S.; Martin, D.; Xiao, Q.; Wang, W.; Jin, Z.G.; Cockerill, G.; Mori, K.; Li, Y.S.; Hu, Y.; Chien, S.; Xu, Q. Sustained activation of XBP1 splicing leads to endothelial apoptosis and atherosclerosis development in response to disturbed flow. Proc. Natl. Acad. Sci. USA, 2009, 106(20), 8326-8331.
[] [PMID: 19416856]
Tufanli, O.; Telkoparan Akillilar, P.; Acosta-Alvear, D.; Kocaturk, B.; Onat, U.I.; Hamid, S.M.; Çimen, I.; Walter, P.; Weber, C.; Erbay, E. Targeting IRE1 with small molecules counteracts progression of atherosclerosis. Proc. Natl. Acad. Sci. USA, 2017, 114(8), E1395-E1404.
[] [PMID: 28137856]
Volkmann, K.; Lucas, J.L.; Vuga, D.; Wang, X.; Brumm, D.; Stiles, C.; Kriebel, D.; Der-Sarkissian, A.; Krishnan, K.; Schweitzer, C.; Liu, Z.; Malyankar, U.M.; Chiovitti, D.; Canny, M.; Durocher, D.; Sicheri, F.; Patterson, J.B. Potent and selective inhibitors of the inositol-requiring enzyme 1 endoribonuclease. J. Biol. Chem., 2011, 286(14), 12743-12755.
[] [PMID: 21303903]
Mimura, N.; Fulciniti, M.; Gorgun, G.; Tai, Y.T.; Cirstea, D.; Santo, L.; Hu, Y.; Fabre, C.; Minami, J.; Ohguchi, H.; Kiziltepe, T.; Ikeda, H.; Kawano, Y.; French, M.; Blumenthal, M.; Tam, V.; Kertesz, N.L.; Malyankar, U.M.; Hokenson, M.; Pham, T.; Zeng, Q.; Patterson, J.B.; Richardson, P.G.; Munshi, N.C.; Anderson, K.C. Blockade of XBP1 splicing by inhibition of IRE1α is a promising therapeutic option in multiple myeloma. Blood, 2012, 119(24), 5772-5781.
[] [PMID: 22538852]
Ri, M.; Tashiro, E.; Oikawa, D.; Shinjo, S.; Tokuda, M.; Yokouchi, Y.; Narita, T.; Masaki, A.; Ito, A.; Ding, J.; Kusumoto, S.; Ishida, T.; Komatsu, H.; Shiotsu, Y.; Ueda, R.; Iwawaki, T.; Imoto, M.; Iida, S. Identification of Toyocamycin, an agent cytotoxic for multiple myeloma cells, as a potent inhibitor of ER stress-induced XBP1 mRNA splicing. Blood Cancer J., 2012, 2(7)e79
[] [PMID: 22852048]
Sanches, M.; Duffy, N.M.; Talukdar, M.; Thevakumaran, N.; Chiovitti, D.; Canny, M.D.; Lee, K.; Kurinov, I.; Uehling, D.; Al-awar, R.; Poda, G.; Prakesch, M.; Wilson, B.; Tam, V.; Schweitzer, C.; Toro, A.; Lucas, J.L.; Vuga, D.; Lehmann, L.; Durocher, D.; Zeng, Q.; Patterson, J.B.; Sicheri, F. Structure and mechanism of action of the hydroxy-aryl-aldehyde class of IRE1 endoribonuclease inhibitors. Nat. Commun., 2014, 5, 4202.
[] [PMID: 25164867]
Wang, S.B.; Wang, Z.Z.; Fan, Q.R.; Guo, J.; Galli, G.; Du, G.H.; Wang, X.; Xiao, W. Ginkgolide K protects the heart against ER stress injury by activating the IRE1 alpha/XBP1 pathway. Acta Pharmacol. Sin., 2017, 38(7), 1075-1075.
[] [PMID: 27186946]
Duan, Q.; Chen, C.; Yang, L.; Li, N.; Gong, W.; Li, S.; Wang, D.W. MicroRNA regulation of unfolded protein response transcription factor XBP1 in the progression of cardiac hypertrophy and heart failure in vivo. J. Transl. Med., 2015, 13, 363.
[] [PMID: 26572862]
Lederkremer, G.Z.; Glickman, M.H. A window of opportunity: timing protein degradation by trimming of sugars and ubiquitins. Trends Biochem. Sci., 2005, 30(6), 297-303.
[] [PMID: 15950873]
Hwang, J.; Qi, L. Quality control in the endoplasmic reticulum: Crosstalk between ERAD and UPR pathways. Trends Biochem. Sci., 2018, 43(8), 593-605.
[] [PMID: 30056836]
Belmont, P.J.; Chen, W.J.; San Pedro, M.N.; Thuerauf, D.J.; Gellings Lowe, N.; Gude, N.; Hilton, B.; Wolkowicz, R.; Sussman, M.A.; Glembotski, C.C. Roles for endoplasmic reticulum-associated degradation and the novel endoplasmic reticulum stress response gene Derlin-3 in the ischemic heart. Circ. Res., 2010, 106(2), 307-316.
[] [PMID: 19940266]
Doroudgar, S.; Völkers, M.; Thuerauf, D.J.; Khan, M.; Mohsin, S.; Respress, J.L.; Wang, W.; Gude, N.; Müller, O.J.; Wehrens, X.H.; Sussman, M.A.; Glembotski, C.C. Hrd1 and ER-associated protein degradation, ERAD, are critical elements of the adaptive ER stress response in cardiac myocytes. Circ. Res., 2015, 117(6), 536-546.
[] [PMID: 26137860]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy