Journal
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
Volume 2014, Issue -, Pages -Publisher
HINDAWI LTD
DOI: 10.1155/2014/746531
Keywords
-
Categories
Funding
- National Natural Sciences Foundation of China [81100541, 81270812, 81470960]
- Doctoral Fund of Ministry of Education of China [20110162110012]
- Furong Scholars Fund from Hunan Province Education
Ask authors/readers for more resources
Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD). Renal tubular injury by overproduction of ROS in mitochondria plays a critical role in the pathogenesis of DKD. Evidences have shown that p66Shc was involved in renal tubular injury via mitochondrial-dependent ROS production pathway, but little is known about the upstream signaling of p66Shc that leads to tubular oxidative damage under high glucose conditions. In this study, an increased PKC delta and p66Shc activation and ROS production in renal tissues of patients with diabetic nephropathy were seen and further analysis revealed a positive correlation between the tubulointerstitial damage and p-PKC delta, p-p66Shc, and ROS production. In vitro, we investigated the phosphorylation and activation of p66Shc and PKC delta during treatment of HK-2 cells with high glucose (HG). Results showed that the activation of p66Shc and PKC delta was increased in a dose-and time-dependent manner, and this effect was suppressed by Rottlerin, a pharmacologic inhibitor of PKC delta. Moreover, PKC delta siRNA partially blocked HG-induced p66Shc phosphorylation, translocation, and ROS production in HK-2 cells. Taken together, these data suggest that activation of PKC delta promotes tubular cell injury through regulating p66Shc phosphorylation and mitochondrial translocation in HG ambient.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available