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

Journal of Translational Medicine

Hongyin Du³  Hengchang Ren¹  Liying Shi⁴  Jingkai Tong²  Kang Cui²  Jianjian Yu⁵  Rubin Xu¹  Mingwei Sheng¹  Wenli Yu¹ 

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

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

Others  :  828163
DOI  :  10.1186/1479-5876-11-24

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

【 摘 要 】

Background

Ischemia/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.

Methods

The 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.

Results

H/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).

Conclusion

This 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】

   
2013 Yu et al; licensee BioMed Central Ltd.

【 图 表 】

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