Suppression of Par-4 protects human renal proximal tubule cells from apoptosis induced by oxidative stress.
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.


OBJECTIVE
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.


CONCLUSIONS
Par-4 gene silencing resulted in PI3K/Akt signaling-dependent inhibition of renal proximal tubular cell apoptosis following oxidative stress.
Sun
Bin
B
Division of Nephrology, Department of Internal Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Lu
Chao
C
Zhou
Guo-Ping
GP
Xing
Chang-Ying
CY
D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics*; D053148:Caspase 3 / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D051017:Apoptosis Regulatory Proteins; D034741:RNA, Small Interfering; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C101296:prostate apoptosis response-4 protein; D006861:Hydrogen Peroxide; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3