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Inhibition of autophagy by berberine enhances the survival of H9C2 myocytes following hypoxia

  • Authors:
    • Zhuyin Jia
    • Lu Lin
    • Shanjun Huang
    • Zhouyang Zhu
    • Weijian Huang
    • Zhouqing Huang
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, Wenzhou Central Hospital, Wenzhou, Zhejiang 325000, P.R. China, Cardiac Center, Department of Cardiology, The Key Laboratory of Cardiovascular Disease of Wenzhou, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
    Copyright: © Jia et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1677-1684
    |
    Published online on: June 14, 2017
       https://doi.org/10.3892/mmr.2017.6770
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Abstract

Hypoxia may induce apoptosis and autophagy to promote cardiomyocyte injury. The present study investigated the effect of berberine, a natural extract of Rhizoma Coptidis, on hypoxia‑induced autophagy and apoptosis in the H9c2 rat myocardial cell line. Expression levels of apoptosis and autophagy markers were upregulated in H9c2 myocytes during hypoxia and cell viability was reduced. However, berberine significantly reduced hypoxia‑induced autophagy in H9c2 myocytes, as demonstrated by the ratio of microtubule‑associated proteins 1A/1B light chain 3 I/II and the expression levels of B‑cell lymphoma 2 (Bcl‑2)/adenovirus E1B 19 kDa protein‑interacting protein 3, and promoted cell viability. In addition, expression levels of the Bcl‑2 anti‑apoptotic protein were significantly downregulated, and expression levels of pro‑apoptotic proteins Bcl‑2‑associated X protein and cleaved caspase‑3 were upregulated during hypoxia injury in cardiac myocytes. This was reversed by treatment with berberine or the autophagy inhibitor 3‑methyladenine, whereas the autophagy agonist rapamycin had the opposite effects, suggesting that berberine reduces myocyte cell death via inhibition of autophagy and apoptosis during hypoxia. In addition, Compound C, a 5' adenosine monophosphate‑activated protein kinase (AMPK) inhibitor, reduced apoptosis and autophagy in hypoxic myocytes, suggesting that the activation of the AMPK signaling pathway may be involved in this process. These findings suggested that berberine protects cells from hypoxia‑induced apoptosis via inhibition of autophagy and suppression of AMPK activation. Therefore, berberine may be a potential therapeutic agent for the treatment of patients with cardiac myocyte injury and ischemia.
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View References

1 

Kelekar A: Autophagy. Ann N Y Acad Sci. 1066:259–271. 2005. View Article : Google Scholar : PubMed/NCBI

2 

Matsui Y, Takagi H, Qu X, Abdellatif M, Sakoda H, Asano T, Levine B and Sadoshima J: Distinct roles of autophagy in the heart during ischemia and reperfusion: Roles of AMP-activated protein kinase and Beclin 1 in mediating autophagy. Circ Res. 100:914–922. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Valentim L, Laurence KM, Townsend PA, Carroll CJ, Soond S, Scarabelli TM, Knight RA, Latchman DS and Stephanou A: Urocortin inhibits Beclin1-mediated autophagic cell death in cardiac myocytes exposed to ischaemia/reperfusion injury. J Mol Cell Cardiol. 40:846–852. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Mizushima N, Levine B, Cuervo AM and Klionsky DJ: Autophagy fights disease through cellular self-digestion. Nature. 451:1069–1075. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Xu J, Qin X, Cai X, Yang L, Xing Y, Li J, Zhang L, Tang Y, Liu J, Zhang X and Gao F: Mitochondrial JNK activation triggers autophagy and apoptosis and aggravates myocardial injury following ischemia/reperfusion. Biochim Biophys Acta. 1852:262–270. 2015. View Article : Google Scholar : PubMed/NCBI

6 

Ferrandi C, Ballerio R, Gaillard P, Giachetti C, Carboni S, Vitte PA, Gotteland JP and Cirillo R: Inhibition of c-Jun N-terminal kinase decreases cardiomyocyte apoptosis and infarct size after myocardial ischemia and reperfusion in anaesthetized rats. Br J Pharmacol. 142:953–960. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Chambers JW, Pachori A, Howard S, Iqbal S and LoGrasso PV: Inhibition of JNK mitochondrial localization and signaling is protective against ischemia/reperfusion injury in rats. J Biol Chem. 288:4000–4011. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Espert L, Denizot M, Grimaldi M, Robert-Hebmann V, Gay B, Varbanov M, Codogno P and Biard-Piechaczyk M: Autophagy is involved in T cell death after binding of HIV-1 envelope proteins to CXCR4. J Clin Invest. 116:2161–2172. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Maiuri MC, Zalckvar E, Kimchi A and Kroemer G: Self-eating and self-killing: Crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol. 8:741–752. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Peng WH, Wu CR, Chen CS, Chen CF, Leu ZC and Hsieh MT: Anxiolytic effect of berberine on exploratory activity of the mouse in two experimental anxiety models: Interaction with drugs acting at 5-HT receptors. Life Sci. 75:2451–2462. 2004. View Article : Google Scholar : PubMed/NCBI

11 

Wang F, Zhao G, Cheng L, Zhou HY, Fu LY and Yao WX: Effects of berberine on potassium currents in acutely isolated CA1 pyramidal neurons of rat hippocampus. Brain Res. 999:91–97. 2004. View Article : Google Scholar : PubMed/NCBI

12 

Zhang M, Wang CM, Li J, Meng ZJ, Wei SN, Li J, Bucala R, Li YL and Chen L: Berberine protects against palmitate-induced endothelial dysfunction: Involvements of upregulation of AMPK and eNOS and downregulation of NOX4. Mediators Inflamm. 2013:2604642013. View Article : Google Scholar : PubMed/NCBI

13 

Heidarian E, Rafieian-Kopaei M, Khoshdel A and Bakhshesh M: Metabolic effects of berberine on liver phosphatidate phosphohydrolase in rats fed on high lipogenic diet: An additional mechanism for the hypolipidemic effects of berberine. Asian Pac J Trop Biomed. 4 Suppl 1:S429–S435. 2014. View Article : Google Scholar : PubMed/NCBI

14 

Vuddanda PR, Chakraborty S and Singh S: Berberine: A potential phytochemical with multispectrum therapeutic activities. Expert Opin Investig Drugs. 19:1297–1307. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Huang Z, Han Z, Ye B, Dai Z, Shan P, Lu Z, Dai K, Wang C and Huang W: Berberine alleviates cardiac ischemia/reperfusion injury by inhibiting excessive autophagy in cardiomyocytes. Eur J Pharmacol. 762:1–10. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Pires EN Simoes, Frozza RL, Hoppe JB, Bde M Menezes and Salbego CG: Berberine was neuroprotective against an in vitro model of brain ischemia: Survival and apoptosis pathways involved. Brain Res. 1557:26–33. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Visnagri A, Kandhare AD and Bodhankar SL: Renoprotective effect of berberine via intonation on apoptosis and mitochondrial-dependent pathway in renal ischemia reperfusion-induced mutilation. Ren Fail. 37:482–493. 2015. View Article : Google Scholar : PubMed/NCBI

18 

Chen K, Li G, Geng F, Zhang Z, Li J, Yang M, Dong L and Gao F: Berberine reduces ischemia/reperfusion-induced myocardial apoptosis via activating AMPK and PI3K-Akt signaling in diabetic rats. Apoptosis. 19:946–957. 2014. View Article : Google Scholar : PubMed/NCBI

19 

Mizushima N and Levine B: Autophagy in mammalian development and differentiation. Nat Cell Biol. 12:823–830. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Deretic V, Saitoh T and Akira S: Autophagy in infection, inflammation and immunity. Nat Rev Immunol. 13:722–737. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Rabinowitz JD and White E: Autophagy and metabolism. Science. 330:1344–1348. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Yan L, Vatner DE, Kim SJ, Ge H, Masurekar M, Massover WH, Yang G, Matsui Y, Sadoshima J and Vatner SF: Autophagy in chronically ischemic myocardium. Proc Natl Acad Sci USA. 102:13807–13812. 2005. View Article : Google Scholar : PubMed/NCBI

23 

Carloni S, Buonocore G and Balduini W: Protective role of autophagy in neonatal hypoxia-ischemia induced brain injury. Neurobiol Dis. 32:329–339. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Jiang M, Liu K, Luo J and Dong Z: Autophagy is a renoprotective mechanism during in vitro hypoxia and in vivo ischemia-reperfusion injury. Am J Pathol. 176:1181–1192. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Hamacher-Brady A, Brady NR and Gottlieb RA: Enhancing macroautophagy protects against ischemia/reperfusion injury in cardiac myocytes. J Biol Chem. 281:29776–29787. 2006. View Article : Google Scholar : PubMed/NCBI

26 

Dosenko VE, Nagibin VS, Tumanovska LV and Moibenko AA: Protective effect of autophagy in anoxia-reoxygenation of isolated cardiomyocyte? Autophagy. 2:305–306. 2006. View Article : Google Scholar : PubMed/NCBI

27 

Nishida K, Yamaguchi O and Otsu K: Crosstalk between autophagy and apoptosis in heart disease. Circ Res. 103:343–351. 2008. View Article : Google Scholar : PubMed/NCBI

28 

Ma X, Liu H, Foyil SR, Godar RJ, Weinheimer CJ, Hill JA and Diwan A: Impaired autophagosome clearance contributes to cardiomyocyte death in ischemia/reperfusion injury. Circulation. 125:3170–3181. 2012. View Article : Google Scholar : PubMed/NCBI

29 

Aki T, Yamaguchi K, Fujimiya T and Mizukami Y: Phosphoinositide 3-kinase accelerates autophagic cell death during glucose deprivation in the rat cardiomyocyte-derived cell line H9c2. Oncogene. 22:8529–8535. 2003. View Article : Google Scholar : PubMed/NCBI

30 

Wang K, Yin XM, Chao DT, Milliman CL and Korsmeyer SJ: BID: A novel BH3 domain-only death agonist. Genes Dev. 10:2859–2869. 1996. View Article : Google Scholar : PubMed/NCBI

31 

Regula KM, Ens K and Kirshenbaum LA: Inducible expression of BNIP3 provokes mitochondrial defects and hypoxia-mediated cell death of ventricular myocytes. Circ Res. 91:226–231. 2002. View Article : Google Scholar : PubMed/NCBI

32 

Bruick RK: Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia. Proc Natl Acad Sci USA. 97:9082–9087. 2000. View Article : Google Scholar : PubMed/NCBI

33 

Kubasiak LA, Hernandez OM, Bishopric NH and Webster KA: Hypoxia and acidosis activate cardiac myocyte death through the Bcl-2 family protein BNIP3. Proc Natl Acad Sci USA. 99:12825–12830. 2002. View Article : Google Scholar : PubMed/NCBI

34 

Wang EY, Gang H, Aviv Y, Dhingra R, Margulets V and Kirshenbaum LA: p53 mediates autophagy and cell death by a mechanism contingent on Bnip3. Hypertension. 62:70–77. 2013. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Jia Z, Lin L, Huang S, Zhu Z, Huang W and Huang Z: Inhibition of autophagy by berberine enhances the survival of H9C2 myocytes following hypoxia. Mol Med Rep 16: 1677-1684, 2017.
APA
Jia, Z., Lin, L., Huang, S., Zhu, Z., Huang, W., & Huang, Z. (2017). Inhibition of autophagy by berberine enhances the survival of H9C2 myocytes following hypoxia. Molecular Medicine Reports, 16, 1677-1684. https://doi.org/10.3892/mmr.2017.6770
MLA
Jia, Z., Lin, L., Huang, S., Zhu, Z., Huang, W., Huang, Z."Inhibition of autophagy by berberine enhances the survival of H9C2 myocytes following hypoxia". Molecular Medicine Reports 16.2 (2017): 1677-1684.
Chicago
Jia, Z., Lin, L., Huang, S., Zhu, Z., Huang, W., Huang, Z."Inhibition of autophagy by berberine enhances the survival of H9C2 myocytes following hypoxia". Molecular Medicine Reports 16, no. 2 (2017): 1677-1684. https://doi.org/10.3892/mmr.2017.6770
Copy and paste a formatted citation
x
Spandidos Publications style
Jia Z, Lin L, Huang S, Zhu Z, Huang W and Huang Z: Inhibition of autophagy by berberine enhances the survival of H9C2 myocytes following hypoxia. Mol Med Rep 16: 1677-1684, 2017.
APA
Jia, Z., Lin, L., Huang, S., Zhu, Z., Huang, W., & Huang, Z. (2017). Inhibition of autophagy by berberine enhances the survival of H9C2 myocytes following hypoxia. Molecular Medicine Reports, 16, 1677-1684. https://doi.org/10.3892/mmr.2017.6770
MLA
Jia, Z., Lin, L., Huang, S., Zhu, Z., Huang, W., Huang, Z."Inhibition of autophagy by berberine enhances the survival of H9C2 myocytes following hypoxia". Molecular Medicine Reports 16.2 (2017): 1677-1684.
Chicago
Jia, Z., Lin, L., Huang, S., Zhu, Z., Huang, W., Huang, Z."Inhibition of autophagy by berberine enhances the survival of H9C2 myocytes following hypoxia". Molecular Medicine Reports 16, no. 2 (2017): 1677-1684. https://doi.org/10.3892/mmr.2017.6770
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