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Current Neurovascular Research

Editor-in-Chief

ISSN (Print): 1567-2026
ISSN (Online): 1875-5739

Research Article

Curcumin Attenuates Cerebral Ischemia-reperfusion Injury Through Regulating Mitophagy and Preserving Mitochondrial Function

Author(s): Weiwei Wang and Jiaping Xu*

Volume 17, Issue 2, 2020

Page: [113 - 122] Pages: 10

DOI: 10.2174/1567202617666200225122620

Price: $65

Abstract

Background: Curcumin, the complex extracted from the traditional edible herb, has a wide range of pharmacological effects. A great deal of studies has demonstrated that curcumin could protect against cerebral ischemia-reperfusion (I/R) injury. In the present study, we aimed to test the hypothesis that curcumin reduces brain damage via regulating mitophagy and preserving mitochondrial function. To clarify the potential effect and mechanism of curcumin on cerebral I/R, we utilize MCAO followed by reperfusion rats and OGD/R neurons as cerebral I/R in vivo and in vitro, respectively.

Methods: We determined the cellular ROS levels and mitochondrial function, including mitochondrial membrane potential (MMP), ATP levels, state 3 respiration and state 4 respiration. We also detected the levels of mitophagy by immunofluorescent staining and western blotting.

Results: Results found that curcumin decreased neurological deficit scores, infarct volume and morphological changes of neurons in rats after brain I/R injury. Curcumin also reduced the levels of ROS while increased MMP, ATP levels and state 3 respiration to prevent the impairment of mitochondrial function from cerebral I/R. Furthermore, curcumin enhanced the co-localization of LC3B and mitochondrial marker VDAC1, the ratio of LC3-II to LC3-I, improving cerebral I/Rinduced mitophagy.

Conclusion: In conclusion, our results suggest that curcumin protects against cerebral I/R injury by improving mitophagy and preserving mitochondrial function.

Keywords: Curcumin, cerebral ischemia-reperfusion, mitochondrial function, mitophagy, mitochondrial membrane potential, ATP.

[1]
Huang L, Chen C, Zhang X, et al. Neuroprotective Effect of curcumin against cerebral ischemia-reperfusion via mediating autophagy and inflammation. J Mol Neurosci 2018; 64(1): 129-39.
[http://dx.doi.org/10.1007/s12031-017-1006-x] [PMID: 29243061]
[2]
Elrod JW, Calvert JW, Morrison J, et al. Hydrogen sulfide attenuates myocardial ischemia-reperfusion injury by preservation of mitochondrial function. Proc Natl Acad Sci USA 2007; 104(39): 15560-5.
[http://dx.doi.org/10.1073/pnas.0705891104] [PMID: 17878306]
[3]
Dagda RK, Cherra SJ III, Kulich SM, Tandon A, Park D, Chu CT. Loss of PINK1 function promotes mitophagy through effects on oxidative stress and mitochondrial fission. J Biol Chem 2009; 284(20): 13843-55.
[http://dx.doi.org/10.1074/jbc.M808515200] [PMID: 19279012]
[4]
Stowe DF, Camara AKS. mitochondrial reactive oxygen species production in excitable cells: modulators of mitochondrial and cell function. Antioxid Redox Signal 2009; 11(6): 1373-414.
[http://dx.doi.org/10.1089/ars.2008.2331] [PMID: 19187004]
[5]
Wu X, Li X, Liu Y, et al. Hydrogen exerts neuroprotective effects on OGD/R damaged neurons in rat hippocampal by protecting mitochondrial function via regulating mitophagy mediated by PINK1/Parkin signaling pathway. Brain Res 2018; 1698: 89-98.
[http://dx.doi.org/10.1016/j.brainres.2018.06.028] [PMID: 29958907]
[6]
Yu S, Zheng S, Leng J, Wang S, Zhao T, Liu J. Inhibition of mitochondrial calcium uniporter protects neurocytes from ischemia/ reperfusion injury via the inhibition of excessive mitophagy. Neurosci Lett 2016; 628: 24-9.
[http://dx.doi.org/10.1016/j.neulet.2016.06.012] [PMID: 27288019]
[7]
Feng J, Chen X, Guan B, Li C, Qiu J, Shen J. Inhibition of peroxynitrite-induced mitophagy activation attenuates cerebral ischemia-reperfusion injury. Mol Neurobiol 2018; 55(8): 6369-86.
[http://dx.doi.org/10.1007/s12035-017-0859-x] [PMID: 29307080]
[8]
Feng J, Chen X, Lu S, et al. Naringin attenuates cerebral ischemia-reperfusion injury through inhibiting peroxynitrite-mediated mitophagy activation. Mol Neurobiol 2018; 55(12): 9029-42.
[http://dx.doi.org/10.1007/s12035-018-1027-7] [PMID: 29627876]
[9]
Zhang Z, Yu J. NR4A1 Promotes cerebral ischemia reperfusion injury by repressing Mfn2-mediated mitophagy and inactivating the MAPK-ERK-CREB signaling pathway. Neurochem Res 2018; 43(10): 1963-77.
[http://dx.doi.org/10.1007/s11064-018-2618-4] [PMID: 30136162]
[10]
Shen Z, Zheng Y, Wu J, et al. PARK2-dependent mitophagy induced by acidic postconditioning protects against focal cerebral ischemia and extends the reperfusion window. Autophagy 2017; 13(3): 473-85.
[http://dx.doi.org/10.1080/15548627.2016.1274596] [PMID: 28103118]
[11]
Trujillo J, Chirino YI, Molina-Jijón E, Andérica-Romero AC, Tapia E, Pedraza-Chaverrí J. Renoprotective effect of the antioxidant curcumin: Recent findings. Redox Biol 2013; 1(1): 448-56.
[http://dx.doi.org/10.1016/j.redox.2013.09.003] [PMID: 24191240]
[12]
de Oliveira MR, Jardim FR, Setzer WN, Nabavi SM, Nabavi SF. Curcumin, mitochondrial biogenesis, and mitophagy: Exploring recent data and indicating future needs. Biotechnol Adv 2016; 34(5): 813-26.
[http://dx.doi.org/10.1016/j.biotechadv.2016.04.004] [PMID: 27143655]
[13]
Li W, Suwanwela NC, Patumraj S. Curcumin by down-regulating NF-kB and elevating Nrf2, reduces brain edema and neurological dysfunction after cerebral I/R. Microvasc Res 2016; 106: 117-27.
[http://dx.doi.org/10.1016/j.mvr.2015.12.008] [PMID: 26686249]
[14]
Wu JX, Zhang LY, Chen YL, Yu SS, Zhao Y, Zhao J. Curcumin pretreatment and post-treatment both improve the antioxidative ability of neurons with oxygen-glucose deprivation. Neural Regen Res 2015; 10(3): 481-9.
[http://dx.doi.org/10.4103/1673-5374.153700] [PMID: 25878600]
[15]
Miao Y, Zhao S, Gao Y, et al. Curcumin pretreatment attenuates inflammation and mitochondrial dysfunction in experimental stroke: The possible role of Sirt1 signaling. Brain Res Bull 2016; 121: 9-15.
[http://dx.doi.org/10.1016/j.brainresbull.2015.11.019] [PMID: 26639783]
[16]
Wicha P, Tocharus J, Janyou A, et al. Hexahydrocurcumin protects against cerebral ischemia/reperfusion injury, attenuates inflammation, and improves antioxidant defenses in a rat stroke model. PLoS One 2017; 12(12): e0189211.
[http://dx.doi.org/10.1371/journal.pone.0189211] [PMID: 29220411]
[17]
Huang L, Chen C, Zhang X, et al. Neuroprotective effect of curcumin against cerebral ischemia-reperfusion via mediating autophagy and inflammation. J Mol Neurosci 2018; 64(1): 129-39.
[http://dx.doi.org/10.1007/s12031-017-1006-x]
[18]
Zhang Y, Fang M, Sun Y, et al. Curcumin attenuates cerebral ischemia injury in Sprague-Dawley rats and PC12 cells by suppressing overactivated autophagy. J Photochem Photobiol B 2018; 184: 1-6.
[http://dx.doi.org/10.1016/j.jphotobiol.2018.05.010] [PMID: 29777940]
[19]
Maiti P, Scott J, Sengupta D, Al-Gharaibeh A, Dunbar GL. Curcumin and solid lipid curcumin particles induce autophagy, but inhibit mitophagy and the PI3K-Akt/mTOR pathway in cultured glioblastoma cells. Int J Mol Sci 2019; 20(2): 399.
[http://dx.doi.org/10.3390/ijms20020399] [PMID: 30669284]
[20]
Kapoor S, Tyagi N, Qipshidze N, Givvimani S, Kandel M, Tyagi SC. Curcumin mitigated ischemic and hyperhomocysteinemic cerebral microvascular mitochondrial mitophagy by decreasing oxidative and inflammatory stresses. FASEB J 2010; 1: 24.https://www.fasebj.org/doi/abs/10.1096/fasebj.24.1_supplement.604.19
[21]
Ortega-Domínguez B, Aparicio-Trejo OE, García-Arroyo FE, et al. Curcumin prevents cisplatin-induced renal alterations in mitochondrial bioenergetics and dynamic. Food Chem Toxicol 2017; 107(Pt A): 373-85.
[http://dx.doi.org/10.1016/j.fct.2017.07.018] [PMID: 28698153]
[22]
Wang X, Leung AW, Luo J, Xu C. TEM observation of ultrasound induced mitophagy in nasopharyngeal carcinoma cells in the presence of curcumin. Exp Ther Med 2012; 3(1): 146-8.
[http://dx.doi.org/10.3892/etm.2011.365] [PMID: 22969860]
[23]
Pan J, Konstas A-A, Bateman B, Ortolano GA, Pile-Spellman J. Reperfusion injury following cerebral ischemia: pathophysiology, MR imaging, and potential therapies. Neuroradiology 2007; 49(2): 93-102.
[http://dx.doi.org/10.1007/s00234-006-0183-z] [PMID: 17177065]
[24]
Tang Y-C, Tian H-X, Yi T, Chen H-B. The critical roles of mitophagy in cerebral ischemia. Protein Cell 2016; 7(10): 699-713.
[http://dx.doi.org/10.1007/s13238-016-0307-0] [PMID: 27554669]
[25]
Youle RJ, Narendra DP. Mechanisms of mitophagy. Nat Rev Mol Cell Biol 2011; 12(1): 9-14.
[http://dx.doi.org/10.1038/nrm3028] [PMID: 21179058]
[26]
Guan R, Zou W, Dai X, et al. Mitophagy, a potential therapeutic target for stroke. J Biomed Sci 2018; 25(1): 87.
[http://dx.doi.org/10.1186/s12929-018-0487-4] [PMID: 30501621]
[27]
Rasola A, Bernardi P. The mitochondrial permeability transition pore and its involvement in cell death and in disease pathogenesis. Apoptosis 2007; 12(5): 815-33.
[http://dx.doi.org/10.1007/s10495-007-0723-y] [PMID: 17294078]
[28]
Pulido-Moran M, Moreno-Fernandez J, Ramirez-Tortosa C, Ramirez-Tortosa M. Curcumin and health. Molecules 2016; 21(3): 264.
[http://dx.doi.org/10.3390/molecules21030264] [PMID: 26927041]
[29]
Jeong G-S, Oh G-S, Pae H-O, et al. Comparative effects of curcuminoids on endothelial heme oxygenase-1 expression: Orthomethoxy groups are essential to enhance heme oxygenase activity and protection. Exp Mol Med 2006; 38(4): 393-400.
[http://dx.doi.org/10.1038/emm.2006.46] [PMID: 16953118]
[30]
Joe B, Lokesh BR. Role of capsaicin, curcumin and dietary n-3 fatty acids in lowering the generation of reactive oxygen species in rat peritoneal macrophages. Biochim Biophys Acta 1994; 1224(2): 255-63.
[http://dx.doi.org/10.1016/0167-4889(94)90198-8] [PMID: 7981240]
[31]
Reddy AC, Lokesh BR. Effect of dietary turmeric (Curcuma longa) on iron-induced lipid peroxidation in the rat liver. Food Chem Toxicol 1994; 32(3): 279-83.
[http://dx.doi.org/10.1016/0278-6915(94)90201-1] [PMID: 8157223]
[32]
Joe B, Vijaykumar M, Lokesh BR. Biological properties of curcumin-cellular and molecular mechanisms of action. Crit Rev Food Sci Nutr 2004; 44(2): 97-111.
[http://dx.doi.org/10.1080/10408690490424702] [PMID: 15116757]
[33]
Detmer SA, Chan DC. Functions and dysfunctions of mitochondrial dynamics. Nat Rev Mol Cell Biol 2007; 8(11): 870-9.
[http://dx.doi.org/10.1038/nrm2275] [PMID: 17928812]
[34]
Zhang X, Yuan Y, Jiang L, et al. Endoplasmic reticulum stress induced by tunicamycin and thapsigargin protects against transient ischemic brain injury: Involvement of PARK2-dependent mitophagy. Autophagy 2014; 10(10): 1801-13.
[http://dx.doi.org/10.4161/auto.32136] [PMID: 25126734]
[35]
Yuan Y, Zheng Y, Zhang X, et al. BNIP3L/NIX-mediated mitophagy protects against ischemic brain injury independent of PARK2. Autophagy 2017; 13(10): 1754-66.
[http://dx.doi.org/10.1080/15548627.2017.1357792] [PMID: 28820284]
[36]
Tyagi N, Qipshidze N, Munjal C, et al. Tetrahydrocurcumin ameliorates homocysteinylated cytochrome-c mediated autophagy in hyperhomocysteinemia mice after cerebral ischemia. J Mol Neurosci 2012; 47(1): 128-38.
[http://dx.doi.org/10.1007/s12031-011-9695-z] [PMID: 22212488]
[37]
Mizushima N, Komatsu M. Autophagy: renovation of cells and tissues. Cell 2011; 147(4): 728-41.
[http://dx.doi.org/10.1016/j.cell.2011.10.026] [PMID: 22078875]
[38]
Zhang J. Autophagy and mitophagy in cellular damage control. Redox Biol 2013; 1(1): 19-23.
[http://dx.doi.org/10.1016/j.redox.2012.11.008] [PMID: 23946931]
[39]
Bravo-San Pedro JM, Kroemer G, Galluzzi L. Autophagy and mitophagy in cardiovascular disease. Circ Res 2017; 120(11): 1812-24.
[http://dx.doi.org/10.1161/CIRCRESAHA.117.311082] [PMID: 28546358]
[40]
Kobayashi S, Liang Q. Autophagy and mitophagy in diabetic cardiomyopathy. Biochim Biophys Acta 2015; 1852(2): 252-61.
[http://dx.doi.org/10.1016/j.bbadis.2014.05.020] [PMID: 24882754]
[41]
Chu CT. Diversity in the regulation of autophagy and mitophagy: Lessons from Parkinson’s disease. Parkinsons Dis 2011; 2011 789431.
[http://dx.doi.org/10.4061/2011/789431] [PMID: 21603187]
[42]
Redmann M, Darley-Usmar V, Zhang J. The role of autophagy, mitophagy and lysosomal functions in modulating bioenergetics and survival in the context of redox and proteotoxic damage: Implications for neurodegenerative diseases. Aging Dis 2016; 7(2): 150-62.
[http://dx.doi.org/10.14336/AD.2015.0820] [PMID: 27114848]

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