Berberine protects human renal proximal tubular cells from hypoxia/reoxygenation injury via inhibiting endoplasmic reticulum and mitochondrial stress pathways

Journal of Translational Medicine

Research

Jianjian Yu¹  Rubin Xu²  Mingwei Sheng²  Wenli Yu²  Hengchang Ren²  Hongyin Du³  Kang Cui⁴  Jingkai Tong⁴  Liying Shi⁵ 

[1] Department of Anesthesiology, Tianjin Chest Hospital, 300051, Tianjin, China;Department of Anesthesiology, Tianjin First Center Hospital, 300192, Tianjin, China;Department of Anesthesiology, Tianjin First Center Hospital, 300192, Tianjin, China;Key Lab for Critical Care Medicine of the Ministry of Health, 300192, Tianjin, China;Department of Immunology, Tianjin Medical University, 300070, Tianjin, China;Department of Microbiology, Tianjin Medical University, 300070, Tianjin, China;

关键词: Berberine;    Kidney;    Apoptosis;    Endoplasmic reticulum stress;    Mitochondria;   

DOI  :  10.1186/1479-5876-11-24

 received in 2012-11-14, accepted in 2013-01-25,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundIschemia/reperfusion injury plays a crucial role in renal transplantation, and represents a significant risk factor for acute renal failure and delayed graft function. The pathophysiological contribution of endoplasmic reticulum and mitochondria stress to ischemia/reperfusion injury has also been highlighted. Berberine (BBR) has been showed to attenuate ischemia/reperfusion injury by inhibiting oxidative stress. The study was carried out to investigate whether the pretreatment of BBR could reduce hypoxia/reoxygenation (H/R)-induced injury by inhibiting mitochondria stress and endoplasmic reticulum stress pathways.MethodsThe cultured human renal proximal tubular cell line HK-2 cells were exposed to 24 h hypoxia (5% CO2, 1% O2, 94% N2) followed by 3 h reoxygenation (5% CO2, 21% O2, 74% N2). And BBR was added to the culture medium 2h prior to the treatment. Then the cell viability, oxidative stress level, morphological change of apoptosis and apoptotic rate were determined. In addition, Western blot analysis was performed to identify the expression of apoptotic pathway parameters, including Bcl-2, Bax and cytochrome C involved in mitochondrial-dependent pathway and ER stress hallmarks such as glucose-regulated protein 78 and CCAAT/enhancer binding protein homologous protein.ResultsH/R produced dramatic injuries in HK-2 cells. The cell viability and the oxidative stress level in group H/R was significantly decreased. The classical morphological change of apoptosis was found, while the apoptotic rate and the expression of proteins involved in mitochondrial stress and endoplasmic reticulum stress pathways increased (p<0.05). Administration of BBR significantly inhibited these H/R induced changes (p<0.05).ConclusionThis study revealed that BBR pretreatment serves a protective role against H/R induced apoptosis of human renal proximal tubular cells, and the mechanism is related to suppression of mitochondrial stress and endoplasmic reticulum stress pathways.

【 授权许可】

Unknown   
© Yu et al; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.