Berberine protects HK-2 cells from hypoxia/reoxygenation induced apoptosis via inhibiting SPHK1 expression

Abstract

Renal ischemia reperfusion injury (RIRI) refers to the irreversible damage for renal function when blood perfusion is recovered after ischemia for an extended period, which is common in clinical surgeries and has been regarded as a major risk for acute renal failures (ARF) that is accompanied with unimaginably high morbidity and mortality. Hypoxia during ischemia followed by reoxygenation via reperfusion serves as a major event contributing to cell apoptosis, which has been widely accepted as the vital pathogenesis in RIRI. Preventing apoptosis in renal tubular epithelial cell has been considered as effective method for blocking RIRI. In this paper, we established a hypoxia/reoxygenation (H/R) injury model in human proximal tubular epithelial HK-2 cells. Here, we found increased SPHK1 levels in H/R injured HK-2 cells, which could be significantly down regulated after berberine treatment. Berberine has been reported to exert a protective effect on H/R-induced apoptosis of HK-2 cells. So, in our present study, we planned to investigate whether SPHK1 participated in the anti-apoptosis process of berberine in H/R injured HK-2 cells. Our study confirmed the protective effect of berberine against H/R-induced apoptosis in HK-2 cells through promoting cells viability, inhibiting cells apoptosis, and down-regulating p-P38, caspase-3, caspase-9 as well as SPHK1, while up regulating the ratio of Bcl-2/Bax. However, SPHK1 overexpression in HK-2 cells induced severe apoptosis, which can be significantly ameliorated with additional berberine treatment. We concluded that berberine could remarkably prevent H/R-induced apoptosis in HK-2 cells through down-regulating SPHK1 expression levels, and the mechanisms included the suppression of p38 MAPK activation and mitochondrial stress pathways.

Synergistic effect of berberine and pentoxifylline in attenuation of acute kidney injury

“…Consequently, cystatin-c is a surrogate biomarker for AKI and should be incorporated in the estimation of GFR. [25] In the present study, cystatin-c serum levels in AKI were elevated significantly compared with the control group. Thus, coadministration of berberine and/or pentoxifylline led to significant renoprotective effect as disclosed by different studies.…”

Propofol Attenuates Hypoxia/Reoxygenation-Induced Apoptosis and Autophagy in HK-2 Cells by Inhibiting JNK Activation

“…After an acute ischemic insult, PTCs are the most sensitive cells to I/R injury, which is mainly due to physiological hypoxia in the medullary region and the high metabolic activity of PTCs 12. In recent years, numerous studies have used PTC models of H/R to investigate mechanisms of renal I/R injury or to search for drugs that lower the risk of I/R injury 1314. Several studies have shown that propofol is an excellent anti-inflammation and anti-oxidation agent, and may help to prevent and treat I/R injury,1516 although the exact mechanisms remain unclear.…”

“…More should be done in future studies to verify the protective effect of propofol on H/R injury particularly with in vivo assay. Also, reoxygenation time may affect the expression levels of related proteins after H/R injury,14 and in this study, we harvested the cells only at 2 h after reoxygenation due to limited resources. Therefore, it would be informative to measure the effects of propofol against H/R injury at different reoxygenation times.…”

Exploring the Mechanism of Laminaria for the Treatment of Alzheimer's Disease based on Network Pharmacology

“…The targets of active components of Laminaria and the targets of AD were imported into a website called Bioinformatics & Evolutionary Genomics (http://bioinformatics.psb.ugent.be/webtools/Venn/), and the overlapping targets were collected. The target-disease and component-target network was created and merged to construct the component-target-disease network model using Cytoscape 3.7.0 software [26].…”