PDGF-BB Preserves Mitochondrial Morphology, Attenuates ROS Production, and Upregulates Neuroglobin in an Astrocytic Model Under Rotenone Insult

Mol Neurobiol. 2018 Apr;55(4):3085-3095. doi: 10.1007/s12035-017-0567-6. Epub 2017 May 2.

Abstract

Platelet-derived growth factor, subtype BB (PDGF-BB) is a mitogenic growth factor produced in different cell types such as platelets, fibroblasts, neurons, and astrocytes. Previous reports have shown that different PDGF isoforms exert a neuroprotective effect in neurons and astrocytes against multiple degenerative insults. Previously, we showed that pretreatment with PDGF-BB for 24 h increased cell viability, preserved nuclear morphology and mitochondrial membrane potential following stimulation with rotenone, and reduced free radical production nearly to control conditions. In the present study, we explored the potential mechanisms associated with PDGF-BB protection against oxidative damage. Our results showed that PDGF-BB protected astrocytic cells through multiple responses, including decrease in the expression of cytoskeleton proteins, attenuated free radicals (reactive oxygen species (ROS)) production, preservation of mitochondrial ultrastructure, and improved expression of neuroglobin (Ngb1). In summary, these findings point out that PDGF-BB protects astrocytic cells by a reduction in ROS production and activation of antioxidant mechanisms.

Keywords: Astrocytes; Mitochondria; Neuroglobin; PDGF-BB; Reactive oxygen species; Rotenone.

MeSH terms

  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Astrocytes / ultrastructure
  • Biomarkers / metabolism
  • Cell Line, Tumor
  • Cytoskeleton / drug effects
  • Cytoskeleton / metabolism
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Mitochondria / ultrastructure
  • NF-kappa B / metabolism
  • Neuroglobin / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Platelet-Derived Growth Factor / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Reactive Oxygen Species / metabolism*
  • Rotenone / toxicity*
  • Signal Transduction / drug effects
  • Up-Regulation / drug effects*

Substances

  • Biomarkers
  • NF-kappa B
  • Neuroglobin
  • Platelet-Derived Growth Factor
  • Reactive Oxygen Species
  • Rotenone
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt