Abstract
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.
Highlights
Ischemia/reperfusion injury plays a crucial role in renal transplantation, and represents a significant risk factor for acute renal failure and delayed graft function
Ischemia/reperfusion injury (IRI), which occurs in 10%-20% of renal transplant (RTx) recipients [1], is a major cause of acute renal failure and increases the risk of delayed graft function and early mortality as well [2]
Protecting proximal tubular cells from IRI has been considered a reasonable strategy for significantly improving short- and long-term outcomes for RTx recipients and potentially expanding the use of “marginal donor organs” which are more susceptible to IRI [5]
Summary
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 been highlighted. 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. Ischemia/reperfusion injury (IRI), which occurs in 10%-20% of renal transplant (RTx) recipients [1], is a major cause of acute renal failure and increases the risk of delayed graft function and early mortality as well [2]. Hypoxia during ischemia and subsequent reoxygenation upon reperfusion are thought to be the major culprits contributing to reactive oxygen species (ROS) production which leads to uncontrolled oxidative stress and the subsequent cell apoptosis [6,7]. Related studies have been done in various cells such as neuronal-like rat pheochromocytoma cells [10], pancreatic β-cells [11] and so on [12], whereas no study has been carried out concerning their relationship in renal proximal tubular cell apoptosis induced by IRI
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