Resveratrol upregulated heat shock proteins and extended the survival of G93A-SOD1 mice

Brain Res. 2012 Nov 5:1483:112-7. doi: 10.1016/j.brainres.2012.09.022. Epub 2012 Sep 19.

Abstract

In the present study, we investigated whether resveratrol, a SIRT1 activator, can suppress the motor neuron degeneration in a transgenic mouse model of amyotrophic lateral sclerosis. Chronic intraperitoneal injection of resveratrol delayed the disease onset and extended survival of the transgenic mice overexpressing G93A-SOD1. The number of surviving motor neurons increased in the resveratrol-injected G93A mice. Importantly, the levels of Hsp25 and Hsp70 were elevated while the level of heat shock factor 1 (HSF1) acetylation decreased in the spinal cords of the resveratrol-injected G93A mice. Our data suggest that resveratrol may protect motor neurons from the mutant SOD1-induced neurotoxicity by promoting SIRT1-mediated deacetylation of HSF1 and subsequent upregulation of Hsps.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / drug therapy*
  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / mortality*
  • Animals
  • Antioxidants / therapeutic use*
  • DNA-Binding Proteins / metabolism
  • Disease Models, Animal
  • Glial Fibrillary Acidic Protein / metabolism
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism
  • Heat Shock Transcription Factors
  • Heat-Shock Proteins / metabolism*
  • Humans
  • Macrophage-1 Antigen / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Molecular Chaperones
  • Motor Neurons / drug effects
  • Neoplasm Proteins / metabolism
  • Resveratrol
  • Spinal Cord / pathology
  • Stilbenes / therapeutic use*
  • Superoxide Dismutase / genetics
  • Survival Analysis
  • Transcription Factors / metabolism
  • Up-Regulation / drug effects*
  • Up-Regulation / genetics

Substances

  • Antioxidants
  • DNA-Binding Proteins
  • Glial Fibrillary Acidic Protein
  • HSP70 Heat-Shock Proteins
  • Heat Shock Transcription Factors
  • Heat-Shock Proteins
  • Hsbp1 protein, mouse
  • Hsf1 protein, mouse
  • Macrophage-1 Antigen
  • Molecular Chaperones
  • Neoplasm Proteins
  • Stilbenes
  • Transcription Factors
  • SOD1 G93A protein
  • Superoxide Dismutase
  • Resveratrol