Signaling mechanisms underlying the glioprotective effects of resveratrol against mitochondrial dysfunction

Biochim Biophys Acta. 2016 Sep;1862(9):1827-38. doi: 10.1016/j.bbadis.2016.06.018. Epub 2016 Jul 1.

Abstract

Resveratrol, a polyphenol found in grapes and red wine, exhibits antioxidant, anti-inflammatory, anti-aging and, neuroprotective effects. Resveratrol also plays a significant role modulating glial functionality, protecting the health of neuroglial cells against several neuropsychiatric in vivo and in vitro experimental models. Mitochondrial impairment strongly affected astrocyte functions and consequently brain homeostasis. Molecules that promote astrocyte mitochondrial protection are fundamental to maintain brain energy balance and cellular redox state, contributing to brain healthy. Thus, the present study was designed to evaluate some glioprotective mechanisms of resveratrol against mitochondrial damage promoted by azide exposure in hippocampal primary astrocyte cultures. Azide treatment provoked deleterious effects, including the dysfunction of mitochondria, the deterioration of redox homeostasis, the augmentation of pro-inflammatory cytokines and impairment of glutamate uptake activity. However, resveratrol prevented these effects, protecting hippocampal astrocytes against azide-induced cytotoxicity through the heme-oxygenase-1 (HO-1) pathway and inhibiting p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor kappa B (NFκB) activation. Resveratrol also protected astrocytes via phosphatidylinositide 3-kinase (PI3K)/Akt. These results contribute to the comprehension of the mechanisms by which resveratrol mediates hippocampal astrocyte protection against mitochondrial failure and implicate resveratrol as an important glioprotective molecule.

Keywords: Heme oxygenase-1 (HO-1); Hippocampal astrocytes; Mitochondrial dysfunction; Nuclear factor kappa B (NFκB); Resveratrol.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • Astrocytes / drug effects*
  • Astrocytes / metabolism*
  • Cells, Cultured
  • Glutamic Acid / metabolism
  • Glutathione / metabolism
  • Heme Oxygenase (Decyclizing) / metabolism
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Male
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Models, Neurological
  • NF-kappa B / metabolism
  • Neuroprotective Agents / pharmacology*
  • Nitrosative Stress / drug effects
  • Oxidative Stress / drug effects
  • Phosphatidylinositol 3-Kinases / metabolism
  • Rats
  • Rats, Wistar
  • Resveratrol / pharmacology*
  • Signal Transduction / drug effects
  • Sodium Azide / toxicity
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Antioxidants
  • NF-kappa B
  • Neuroprotective Agents
  • Glutamic Acid
  • Sodium Azide
  • Heme Oxygenase (Decyclizing)
  • Hmox1 protein, rat
  • Phosphatidylinositol 3-Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Glutathione
  • Resveratrol