Generic placeholder image

Current Bioactive Compounds

Editor-in-Chief

ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

General Research Article

Nano-Curcumin Regulates p53 Phosphorylation and PAI-1 Expression during Bleomycin Induced Injury in Alveolar Basal Epithelial Cells

Author(s): Mahesh M. Gouda, Ashwini Prabhu, Varsha Reddy S.V., Rafa Jahan and Yashodhar P. Bhandary*

Volume 16, Issue 1, 2020

Page: [85 - 89] Pages: 5

DOI: 10.2174/1573407214666180727093612

Price: $65

Abstract

Background: Bleomycin (BLM) is known to cause DNA damage in the Alveolar Epithelial Cells (AECs). It is reported that BLM is involved in the up-regulation of inflammatory molecules such as neutrophils, macrophages, chemokines and cytokines. The complex underlying mechanism for inflammation mediated progression of lung injury is still unclear. This investigation was designed to understand the molecular mechanisms associated with p53 mediated modulation of Plasminogen Activator Inhibitor-I (PAI-I) expression and its regulation by nano-curcumin formulation.

Methods: A549 cells were treated with BLM to cause the cellular damage in vitro and commercially available nano-curcumin formulation was used as an intervention. Cytotoxic effect of nano-curcumin was analyzed using Methyl Thiazolyl Tetrazolium (MTT) assay. Protein expressions were analyzed using western blot to evaluate the p53 mediated changes in PAI-I expression.

Results: Nano-curcumin showed cytotoxicity up to 88.5 % at a concentration of 20 μg/ml after 48 h of treatment. BLM exposure to the cells activated the phosphorylation of p53, which in turn increased PAII expression. Nano-curcumin treatment showed a protective role against phosphorylation of p53 and PAI-I expression, which in turn regulated the fibro-proliferative phase of injury induced by bleomycin.

Conclusion: Nano-curcumin could be used as an effective intervention to regulate the severity of lung injury, apoptosis of AECs and fibro-proliferation during pulmonary injury.

Keywords: Lung injury, bleomycin, nano-curcumin, P-p53, PAI-1, Alveolar Epithelial Cells (AECs).

Graphical Abstract
[1]
Bhandary, Y.P.; Shetty, S.K.; Marudamuthu, A.S.; Gyetko, M.R.; Idell, S.; Gharaee-Kermani, M.; Shetty, R.S.; Starcher, B.C.; Shetty, S. Regulation of alveolar epithelial cell apoptosis and pulmonary fibrosis by coordinate expression of components of the fibrinolytic system. Am. J. Physiol. Lung Cell. Mol. Physiol., 2012, 302(5), L463-L473.
[http://dx.doi.org/10.1152/ajplung.00099.2011] [PMID: 22140072]
[2]
Goss, C.H.; Brower, R.G.; Hudson, L.D.; Rubenfeld, G.D. ARDS Network. Incidence of acute lung injury in the United States. Crit. Care Med., 2003, 31(6), 1607-1611.
[http://dx.doi.org/10.1097/01.CCM.0000063475.65751.1D] [PMID: 12794394]
[3]
Hay, J.; Shahzeidi, S.; Laurent, G. Mechanisms of bleomycin-induced lung damage. Arch. Toxicol., 1991, 65(2), 81-94.
[http://dx.doi.org/10.1007/BF02034932] [PMID: 1711838]
[4]
Kinder, B.W.; Brown, K.K.; Schwarz, M.I.; Ix, J.H.; Kervitsky, A.; King, T.E., Jr Baseline BAL neutrophilia predicts early mortality in idiopathic pulmonary fibrosis. Chest, 2008, 133(1), 226-232.
[http://dx.doi.org/10.1378/chest.07-1948] [PMID: 18071016]
[5]
Tomas, R.; Clarissa, S.; Fredarico, A. Review article on bleomycin induced lung injury. Cancer Res., 2013, 2013, 1-9.
[6]
Shi, K.; Jiang, J.; Ma, T.; Xie, J.; Duan, L.; Chen, R.; Song, P.; Yu, Z.; Liu, C.; Zhu, Q.; Zheng, J. Pathogenesis pathways of idiopathic pulmonary fibrosis in bleomycin-induced lung injury model in mice. Respir. Physiol. Neurobiol., 2014, 190, 113-117.
[http://dx.doi.org/10.1016/j.resp.2013.09.011] [PMID: 24140943]
[7]
Gouda, M.M.; Prabhu, A.; Bhandary, Y.P. Curcumin alleviates IL-17A-mediated p53-PAI-1 expression in bleomycin-induced alveolar basal epithelial cells. J. Cell. Biochem., 2018, 119(2), 2222-2230.
[http://dx.doi.org/10.1002/jcb.26384] [PMID: 28902433]
[8]
Ashcroft, M.; Kubbutat, M.H.; Vousden, K.H. Regulation of p53 function and stability by phosphorylation. Mol. Cell. Biol., 1999, 19(3), 1751-1758.
[http://dx.doi.org/10.1128/MCB.19.3.1751] [PMID: 10022862]
[9]
Bhandary, Y.P.; Shetty, S.K.; Marudamuthu, A.S.; Ji, H.L.; Neuenschwander, P.F.; Boggaram, V.; Morris, G.F.; Fu, J.; Idell, S.; Shetty, S. Regulation of lung injury and fibrosis by p53-mediated changes in urokinase and plasminogen activator inhibitor-1. Am. J. Pathol., 2013, 183(1), 131-143.
[http://dx.doi.org/10.1016/j.ajpath.2013.03.022] [PMID: 23665346]
[10]
Shetty, S.; Shetty, P.; Idell, S.; Velusamy, T.; Bhandary, Y.P.; Shetty, R.S. Regulation of plasminogen activator inhibitor-1 expression by tumor suppressor protein p53. J. Biol. Chem., 2008, 283(28), 19570-19580.
[http://dx.doi.org/10.1074/jbc.M710268200] [PMID: 18469003]
[11]
Bai, L.; Zhu, W.G. p53: structure, function and therapeutic applications. J. Cancer Mol., 2006, 2, 141-153.
[12]
Florova, G.; Azghani, A.; Karandashova, S.; Schaefer, C.; Koenig, K.; Stewart-Evans, K.; Declerck, P.J.; Idell, S.; Komissarov, A.A. Targeting of plasminogen activator inhibitor 1 improves fibrinolytic therapy for tetracycline-induced pleural injury in rabbits. Am. J. Respir. Cell Mol. Biol., 2015, 52(4), 429-437.
[http://dx.doi.org/10.1165/rcmb.2014-0168OC] [PMID: 25140386]
[13]
Khimenko, P.L.; Barnard, J.W.; Moore, T.M.; Wilson, P.S.; Ballard, S.T.; Taylor, A.E. Vascular permeability and epithelial transport effects on lung edema formation in ischemia and reperfusion. J. Appl. Physiol., 1994, 77(3), 1116-1121.
[http://dx.doi.org/10.1152/jappl.1994.77.3.1116] [PMID: 7836112]
[14]
McAuley, D.F.; Frank, J.A.; Fang, X.; Matthay, M.A. Clinically relevant concentrations of beta2-adrenergic agonists stimulate maximal cyclic adenosine monophosphate-dependent airspace fluid clearance and decrease pulmonary edema in experimental acid-induced lung injury. Crit. Care Med., 2004, 32(7), 1470-1476.
[http://dx.doi.org/10.1097/01.CCM.0000129489.34416.0E] [PMID: 15241090]
[15]
Merx, M.W.; Liehn, E.A.; Janssens, U.; Lütticken, R.; Schrader, J.; Hanrath, P.; Weber, C. HMG-CoA reductase inhibitor simvastatin profoundly improves survival in a murine model of sepsis. Circulation, 2004, 109(21), 2560-2565.
[http://dx.doi.org/10.1161/01.CIR.0000129774.09737.5B] [PMID: 15123521]
[16]
Meduri, G.U.; Bridges, L.; Shih, M.C.; Marik, P.E.; Siemieniuk, R.A.C.; Kocak, M. Prolonged glucocorticoid treatment is associated with improved ARDS outcomes: analysis of individual patients’ data from four randomized trials and trial-level meta-analysis of the updated literature. Intensive Care Med., 2016, 42(5), 829-840.
[http://dx.doi.org/10.1007/s00134-015-4095-4] [PMID: 26508525]
[17]
Ding, X.M.; Pan, L.; Wang, Y.; Xu, Q.Z. Baicalin exerts protective effects against lipopolysaccharide-induced acute lung injury by regulating the crosstalk between the CX3CL1-CX3CR1 axis and NF-κB pathway in CX3CL1-knockout mice. Int. J. Mol. Med., 2016, 37(3), 703-715.
[http://dx.doi.org/10.3892/ijmm.2016.2456] [PMID: 26782291]
[18]
Liu, L.; Li, H.; Guo, Z.; Ma, X.; Cao, N.; Zheng, Y.; Geng, S.; Duan, Y.; Han, G.; Du, G. The combination of three natural compounds effectively prevented lung carcinogenesis by optimal wound healing. PLoS One, 2015, 10(11)e0143438
[http://dx.doi.org/10.1371/journal.pone.0143438] [PMID: 26599445]
[19]
Jagetia, G.C.; Aggarwal, B.B. “Spicing up” of the immune system by curcumin. J. Clin. Immunol., 2007, 27(1), 19-35.
[http://dx.doi.org/10.1007/s10875-006-9066-7] [PMID: 17211725]
[20]
Punithavathi, D.; Venkatesan, N.; Babu, M. Curcumin inhibition of bleomycin-induced pulmonary fibrosis in rats. Br. J. Pharmacol., 2000, 131(2), 169-172.
[http://dx.doi.org/10.1038/sj.bjp.0703578] [PMID: 10991907]
[21]
Gopal, J.; Muthu, M.; Chun, S.C. One-step, ultrasonication-mobilized, solvent-free extraction/synthesis of nanocurcumin from turmeric. RSC Advances, 2015, 5, 48391-48398.
[http://dx.doi.org/10.1039/C5RA06002H]
[22]
Bisht, S.; Feldmann, G.; Soni, S.; Ravi, R.; Karikar, C.; Maitra, A.; Maitra, A. Polymeric nanoparticle-encapsulated curcumin (“nanocurcumin”): a novel strategy for human cancer therapy. J. Nanobiotechnology, 2007, 5, 3.
[http://dx.doi.org/10.1186/1477-3155-5-3] [PMID: 17439648]
[23]
Goel, A.; Kunnumakkara, A.B.; Aggarwal, B.B. Curcumin as “Curecumin”: from kitchen to clinic. Biochem. Pharmacol., 2008, 75(4), 787-809.
[http://dx.doi.org/10.1016/j.bcp.2007.08.016] [PMID: 17900536]
[24]
López-Lázaro, M. Anticancer and carcinogenic properties of curcumin: considerations for its clinical development as a cancer chemopreventive and chemotherapeutic agent. Mol. Nutr. Food Res., 2008, 52(Suppl. 1), S103-S127.
[http://dx.doi.org/10.1002/mnfr.200700238] [PMID: 18496811]
[25]
Khosropanah, M.H.; Dinarvand, A.; Nezhadhosseini, A.; Haghighi, A.; Hashemi, S.; Nirouzad, F.; Khatamsaz, S.; Entezari, M.; Hashemi, M.; Dehghani, H. Analysis of the antiproliferative effects of curcumin and nanocurcumin in MDA-MB231 as a breast cancer cell line. Iran. J. Pharm. Res., 2016, 15(1), 231-239.
[PMID: 27610163]
[26]
Bhandary, Y.P.; Shetty, S.K.; Marudamuthu, A.S.; Midde, K.K.; Ji, H.L.; Shams, H.; Subramaniam, R.; Fu, J.; Idell, S.; Shetty, S. Plasminogen activator inhibitor-1 in cigarette smoke exposure and influenza A virus infection-induced lung injury. PLoS One, 2015, 10(5)e0123187
[http://dx.doi.org/10.1371/journal.pone.0123187] [PMID: 25932922]
[27]
Gouda, M.M.; Bhandary, Y.P. Curcumin down-regulates IL-17A mediated p53-fibrinolytic system in bleomycin induced acute lung injury in vivo. J. Cell. Biochem., 2018, 119(9), 7285-7299.
[http://dx.doi.org/10.1002/jcb.27026] [PMID: 29775223]

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