Knockdown of thioredoxin interacting protein attenuates high glucose-induced apoptosis and activation of ASK1 in mouse mesangial cells

FEBS Lett. 2011 Jun 23;585(12):1789-95. doi: 10.1016/j.febslet.2011.04.021. Epub 2011 Apr 15.

Abstract

Mesangial cell apoptosis contributes to the pathogenesis of diabetic nephropathy. Here we show that thioredoxin interacting protein (TXNIP) is involved in high glucose (HG)-induced mouse mesangial cell (MMC) apoptosis. HG induced activation of apoptosis signal regulating kinase-1 (ASK1) in a time-dependent manner in MMCs. Treatment with antioxidant, tempol, or knockdown of TXNIP in MMCs reduced HG-mediated apoptosis, expression of cleaved caspase-3, Bax/Bcl-2 ratio and activation of ASK1. These data suggest that knockdown of TXNIP prevented HG-induced cell apoptosis and activation of ASK1 may be via reduction of oxidative stress in MMCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Apoptosis / drug effects*
  • Carrier Proteins / physiology*
  • Enzyme Activation / drug effects*
  • Glucose / pharmacology*
  • MAP Kinase Kinase Kinase 5 / metabolism*
  • Mesangial Cells / cytology
  • Mesangial Cells / metabolism*
  • Mice
  • Mice, Knockout
  • Oxidative Stress
  • Thioredoxins / physiology*

Substances

  • Antioxidants
  • Carrier Proteins
  • Txnip protein, mouse
  • Thioredoxins
  • MAP Kinase Kinase Kinase 5
  • Map3k5 protein, mouse
  • Glucose