High glucose induces podocyte apoptosis by stimulating TRPC6 via elevation of reactive oxygen species

Biochim Biophys Acta. 2013 Jun;1833(6):1434-42. doi: 10.1016/j.bbamcr.2013.02.031. Epub 2013 Mar 13.

Abstract

Podocyte number is significantly reduced in diabetic patients and animal models, but the mechanism remains unclear. In the present study, we found that high glucose induced apoptosis in control podocytes which express transient receptor potential canonical 6 (TRPC6) channels, but not in TRPC6 knockdown podocytes in which TRPC6 was knocked down by TRPC6 silencing short hairpin RNA (shRNA). This effect was reproduced by treatment of podocytes with the reactive oxygen species (ROS), hydrogen peroxide (H2O2). Single-channel data from cell-attached, patch-clamp experiments showed that both high glucose and H2O2 activated the TRPC6 channel in control podocytes, but not in TRPC6 knockdown podocytes. Confocal microscopy showed that high glucose elevated ROS in podocytes and that H2O2 reduced the membrane potential of podocytes and elevated intracellular Ca(2+) via activation of TRPC6. Since intracellular Ca(2+) overload induces apoptosis, H2O2-induced apoptosis may result from TRPC6-mediated elevation of intracellular Ca(2+). These data together suggest that high glucose induces apoptosis in podocytes by stimulating TRPC6 via elevation of ROS.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Apoptosis / drug effects*
  • Blotting, Western
  • Calcium / metabolism*
  • Cells, Cultured
  • Glucose / pharmacology*
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Membrane Potentials / drug effects
  • Oxidants / pharmacology
  • Patch-Clamp Techniques
  • Podocytes / drug effects
  • Podocytes / metabolism
  • Podocytes / pathology*
  • Reactive Oxygen Species / metabolism*
  • Sweetening Agents / pharmacology*
  • TRPC Cation Channels / metabolism*
  • TRPC6 Cation Channel

Substances

  • Oxidants
  • Reactive Oxygen Species
  • Sweetening Agents
  • TRPC Cation Channels
  • TRPC6 Cation Channel
  • TRPC6 protein, human
  • Hydrogen Peroxide
  • Glucose
  • Calcium