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High glucose modifies transient receptor potential canonical type 6 channels via increased oxidative stress and syndecan-4 in human podocytes

Item Type:Article
Title:High glucose modifies transient receptor potential canonical type 6 channels via increased oxidative stress and syndecan-4 in human podocytes
Creators Name:Thilo, F. and Lee, M. and Xia, S. and Zakrzewicz, A. and Tepel, M.
Abstract:Transient receptor potential canonical (TRPC) channels type 6 play an important role in the function of human podocytes. Diabetic nephropathy is characterized by altered TRPC6 expression and functions of podocytes. Thus, we hypothesized that high glucose modifies TRPC6 channels via increased oxidative stress and syndecan-4 (SDC-4) in human podocytes. Human podocytes were exposed to control conditions (5.6mmol/L d-glucose), high glucose (30mmol/L d-glucose or l-glucose), 100mumol/L peroxynitrite, or high glucose and the superoxide dismutase mimetic tempol (100mumol/L). TRPC6 and SDC-4 transcripts and protein expression were measured using RT-PCR and in-cell Western assay. Intracellular reactive oxygen species (ROS) and cytosolic calcium were measured using fluorescent dye techniques. High d-glucose increased TRPC6 transcripts to 8.66+/-4.08 (p<0.05) and TRPC6 protein expression to 1.44+/-0.07 (p<0.05) without altering SDC-4 transcripts or protein expression. The d-glucose induced increase of TRPC6 expression was blocked by tempol. Increased oxidative stress using peroxynitrite significantly increased TRPC6 transcripts to 4.29+/-1.26 (p<0.05) and TRPC6 protein expression to 1.28+/-0.05 (p<0.05) without altering SDC-4 transcripts or protein expression. In human podocytes transfected with scrambled siRNA, high d-glucose increased ROS after 90min to 3.55+/-0.08 arbitrary units while 5.6mmol/L d-glucose increased ROS to 2.49+/-0.09 (p<0.001) only. The increase in ROS was inhibited by tempol and by SDC-4 knockdown. High glucose modifies TRPC6 channels and ROS production via SDC-4 in human podocytes.
Keywords:Diabetic Nephropathy, Podocytes, Transient Receptor Potential Channels, Syndecan-4, High Glucose, Oxidative Stress
Source:Biochemical and Biophysical Research Communications
ISSN:0006-291X
Publisher:Elsevier / Academic Press (U.S.A.)
Volume:450
Number:1
Page Range:312-317
Date:18 July 2014
Official Publication:https://doi.org/10.1016/j.bbrc.2014.05.116
PubMed:View item in PubMed

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