Protective Effect of Gigantol Against Hydrogen peroxide‑induced Apoptosis in Rat Bone Marrow Mesenchymal Stem Cells Through the PI3K/Akt Pathway

Mol Med Rep. 2018 Feb;17(2):3267-3273. doi: 10.3892/mmr.2017.8242. Epub 2017 Dec 11.

Abstract

Bone marrow mesenchymal stem cell (BMSC) transplants are promising for the treatment of certain central nervous system diseases. However, oxidative stress is one of the major factors that may limit the survival of the transplanted BMSCs. The present study investigated the effect of pretreatment with gigantol on hydrogen peroxide (H2O2)‑induced apoptosis in rat BMSCs (rBMSCs) and the potential underlying mechanisms. The results demonstrated that gigantol pretreatment significantly inhibited H2O2‑induced apoptosis of rBMSCs. rBMSCs were incubated with 600 µM H2O2 in the absence or presence of different doses of gigantol (1‑100 µM). Cell viability and apoptosis ratios were assessed by MTT assays and flow cytometry, respectively. Morphological alterations and reactive oxygen species were measured by the fluorescent‑based methods of Hoechst staining and dichlorodihydrofluorescein diacetate, respectively. Furthermore, the protein levels of phosphorylated‑protein kinase B (Akt), B‑cell lymphoma‑2 (Bcl‑2), Bcl‑2‑associated X (Bax), caspase‑3 and caspase‑9 were investigated by western blotting. Following incubation with H2O2 for 2 h, gigantol significantly inhibited the H2O2‑induced reductions in the cell viability of rBMSCs in a dose‑dependent manner. Furthermore, gigantol upregulated Akt phosphorylation and Bcl‑2 expression, downregulated Bax expression, and reduced the expression of caspase‑3 and caspase‑9 in H2O2‑treated rBMSCs, whereas an opposite effect was detected when LY294002, an inhibitor of phosphatidylinositol 3‑kinase, was administered in combination with gigantol. These results indicate that gigantol may be developed as a promising neuroprotective agent for successful MSC transplantation in ischemic diseases.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects*
  • Bibenzyls / pharmacology*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cytoprotection / drug effects
  • Guaiacol / analogs & derivatives*
  • Guaiacol / pharmacology
  • Hydrogen Peroxide / metabolism
  • Male
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / metabolism
  • Oxidative Stress / drug effects*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects*

Substances

  • Antioxidants
  • Bibenzyls
  • Reactive Oxygen Species
  • gigantol
  • Guaiacol
  • Hydrogen Peroxide
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt