Suppression of Par-4 Protects Human Renal Proximal Tubule Cells from Apoptosis Induced by Oxidative Stress

Abstract

Background: Oxidative stress is an important inducer of cell apoptosis and plays a key role in the development of renal inflammation. The prostate apoptosis response factor-4 (Par-4) gene was originally identified in prostate cells undergoing apoptosis. Subsequently, Par-4 was found to possess potent pro-apoptotic activity in various cellular systems. However, it remains unclear whether Par-4 is involved in oxidant injury of renal tubular epithelial cells. Aims: To determine the role of Par-4 in renal proximal tubular cell apoptosis induced by oxidative stress. Methods: Par-4 gene expression was silenced by small interfering RNA. Renal proximal tubular cells were then exposed to hydrogen peroxide and the effect of Par-4 silencing on apoptosis and expression of phosphorylated Akt and vascular endothelial growth factor was determined. Results: Hydrogen peroxide induced apoptosis and increased Par-4 expression in human renal proximal tubular epithelial cells. Par-4 silencing significantly protected renal proximal tubular cells from apoptosis via activating the PI3K/Akt signaling pathway as Akt phosphorylation was enhanced. Par-4 silencing also ameliorated the downregulation of vascular endothelial growth factor expression induced by oxidative stress. Conclusion: Par-4 gene silencing resulted in PI3K/Akt signaling-dependent inhibition of renal proximal tubular cell apoptosis following oxidative stress.

Role of upstream stimulatory factor 2 in glutamate dehydrogenase gene transcription

“…As for Gdh, starvation decreased hepatic mRNA levels of Usf2 in the liver of S. aurata. In this regard, it was previously reported that high glucose levels upregulate Usf2 expression in human-derived HK-2 cells and primary rat mesangial cells (Shi et al 2008, Visavadiya et al 2011, Wang 2015. Therefore, low levels of glycemya associated to long-term starvation may be critical to downregulate Usf2 expression, which in turn may lead to decreased Gdh mRNA levels in the liver of S. aurata.…”

A Rheostat of Ceramide and Sphingosine-1-Phosphate as a Determinant of Oxidative Stress-Mediated Kidney Injury

“…Conversely, IGF-1 activated SphK1 and this effect was mediated by ERK/PI3K/Akt in ECs [ 247 ]. Furthermore, H 2 O 2 downregulated VEGF via inhibition of theh PI3K/Akt pathway, leading to apoptosis in RTCs [ 248 ]. However, SphK1-mediated IGFBP-3 activated VEGF, which resulted in angiogenesis [ 249 ].…”