Berberine Attenuates Mitochondrial Dysfunction by Inducing Autophagic Flux in Myocardial Hypoxia/reoxygenation Injury

Overview

Journal Cell Stress Chaperones

Publisher Elsevier

Specialty Cell Biology

Date 2020 Feb 24

PMID 32088907

Citations 10

Authors

Na Zhu

Xueming Cao

Peiyuan Hao

Yuwei Zhang

Yan Chen

Jing Zhang

Jiang Li

Chuanyu Gao

Li Li

Affiliations

Soon will be listed here.

Abstract

Berberine (BBR) is routinely prescribed in many Asian countries to treat diarrhea. Evidence from both animal and clinical investigations suggests that BBR exerts diverse pharmacological activities, including antidiabetic, antineoplastic, antihypertensive, and antiatherosclerotic effects. This study aimed to explore the cardioprotective mechanisms of BBR and to elucidate the modulations between autophagy and mitochondrial function during hypoxia/reoxygenation (H/R) in H9c2 cells. The degree of autophagic flux was assessed by pretreating H9c2 cells with BBR prior to H/R exposure and measuring the expression levels of Beclin-1 and green fluorescent protein (GFP)-labeled LC3B fusion proteins as well as the LC3II/LC3I ratio. The mitochondrial membrane potential (△Ψm) in H9c2 cells was evaluated by detecting rhodamine-123 fluorescence using flow cytometry. The results revealed that pretreatment with BBR upregulated autophagic flux and protected against the loss of the △Ψm in H9c2 cells subjected to H/R. We conclude that BBR attenuates mitochondrial dysfunction by inducing autophagic flux.

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References

Fan T, Huang Z, Chen L, Wang W, Zhang B, Xu Y . Associations between autophagy, the ubiquitin-proteasome system and endoplasmic reticulum stress in hypoxia-deoxygenation or ischemia-reperfusion. Eur J Pharmacol. 2016; 791:157-167. DOI: 10.1016/j.ejphar.2016.08.026. View

Zhang W, Su X, Gao Y, Sun B, Yu Y, Wang X . Berberine protects mesenchymal stem cells against hypoxia-induced apoptosis in vitro. Biol Pharm Bull. 2009; 32(8):1335-42. DOI: 10.1248/bpb.32.1335. View

Ravaux J, Leger N, Hamel G, Shillito B . Assessing a species thermal tolerance through a multiparameter approach: the case study of the deep-sea hydrothermal vent shrimp Rimicaris exoculata. Cell Stress Chaperones. 2019; 24(3):647-659. PMC: 6527734. DOI: 10.1007/s12192-019-01003-0. View

Huang Z, Han Z, Ye B, Dai Z, Shan P, Lu Z . Berberine alleviates cardiac ischemia/reperfusion injury by inhibiting excessive autophagy in cardiomyocytes. Eur J Pharmacol. 2015; 762:1-10. DOI: 10.1016/j.ejphar.2015.05.028. View

Liu J, Chan P, Chen Y, Tomlinson B, Hong S, Cheng J . The antihypertensive effect of the berberine derivative 6-protoberberine in spontaneously hypertensive rats. Pharmacology. 1999; 59(6):283-9. DOI: 10.1159/000028331. View

Dosenko V, Nagibin V, Tumanovska L, Moibenko A . Protective effect of autophagy in anoxia-reoxygenation of isolated cardiomyocyte?. Autophagy. 2006; 2(4):305-6. DOI: 10.4161/auto.2946. View

Thu V, Kim H, Long L, Lee S, Hanh T, Ko T . NecroX-5 prevents hypoxia/reoxygenation injury by inhibiting the mitochondrial calcium uniporter. Cardiovasc Res. 2012; 94(2):342-50. DOI: 10.1093/cvr/cvs122. View

Choi A, Ryter S, Levine B . Autophagy in human health and disease. N Engl J Med. 2013; 368(7):651-62. DOI: 10.1056/NEJMra1205406. View

Przyklenk K, Dong Y, Undyala V, Whittaker P . Autophagy as a therapeutic target for ischaemia /reperfusion injury? Concepts, controversies, and challenges. Cardiovasc Res. 2012; 94(2):197-205. DOI: 10.1093/cvr/cvr358. View

10.

Xu M, Wang J, Chen L, Wang Y, Yang Z, Tao J . Berberine-induced mobilization of circulating endothelial progenitor cells improves human small artery elasticity. J Hum Hypertens. 2007; 22(6):389-93. DOI: 10.1038/sj.jhh.1002311. View

11.

Cohen I, Castedo M, Kroemer G . Tantalizing Thanatos: unexpected links in death pathways. Trends Cell Biol. 2002; 12(7):293-5. DOI: 10.1016/s0962-8924(02)02299-7. View

12.

Cook S, Sugden P, Clerk A . Regulation of bcl-2 family proteins during development and in response to oxidative stress in cardiac myocytes: association with changes in mitochondrial membrane potential. Circ Res. 1999; 85(10):940-9. DOI: 10.1161/01.res.85.10.940. View

13.

Fang X, Zhang M, Guo J, Jin Z . Effects of insulin-like growth factor-1 on endoplasmic reticulum stress and autophagy in rat gastric smooth muscle cells cultured at different glucose concentrations in vitro. Mol Cell Biochem. 2018; 451(1-2):11-20. DOI: 10.1007/s11010-018-3388-7. View

14.

Wang Y, Huang Y, Lam K, Li Y, Wong W, Ye H . Berberine prevents hyperglycemia-induced endothelial injury and enhances vasodilatation via adenosine monophosphate-activated protein kinase and endothelial nitric oxide synthase. Cardiovasc Res. 2009; 82(3):484-92. DOI: 10.1093/cvr/cvp078. View

15.

Sadoshima J . The role of autophagy during ischemia/reperfusion. Autophagy. 2008; 4(4):402-3. DOI: 10.4161/auto.5924. View

16.

Morimoto H, Hirose M, Takahashi M, Kawaguchi M, Ise H, Kolattukudy P . MCP-1 induces cardioprotection against ischaemia/reperfusion injury: role of reactive oxygen species. Cardiovasc Res. 2008; 78(3):554-62. DOI: 10.1093/cvr/cvn035. View

17.

Tan Y, Ouyang H, Xiao X, Zhong J, Dong M . Irisin ameliorates septic cardiomyopathy via inhibiting DRP1-related mitochondrial fission and normalizing the JNK-LATS2 signaling pathway. Cell Stress Chaperones. 2019; 24(3):595-608. PMC: 6527615. DOI: 10.1007/s12192-019-00992-2. View

18.

Romuk E, Jachec W, Kozielska-Nowalany E, Birkner E, Zemla-Woszek A, Wojciechowska C . Superoxide dismutase activity as a predictor of adverse outcomes in patients with nonischemic dilated cardiomyopathy. Cell Stress Chaperones. 2019; 24(3):661-673. PMC: 6527540. DOI: 10.1007/s12192-019-00991-3. View

19.

Li C, Guan X, Wang R, Xie Y, Zhou H, Ni W . Berberine mitigates high glucose-induced podocyte apoptosis by modulating autophagy via the mTOR/P70S6K/4EBP1 pathway. Life Sci. 2020; 243:117277. DOI: 10.1016/j.lfs.2020.117277. View

20.

Kupatt C, Weber C, Wolf D, Becker B, Smith T, Kelly R . Nitric oxide attenuates reoxygenation-induced ICAM-1 expression in coronary microvascular endothelium: role of NFkappaB. J Mol Cell Cardiol. 1997; 29(10):2599-609. DOI: 10.1006/jmcc.1997.0439. View