Diva reduces cell death in response to oxidative stress and cytotoxicity

PLoS One. 2012;7(8):e43180. doi: 10.1371/journal.pone.0043180. Epub 2012 Aug 15.

Abstract

Diva is a member of the Bcl2 family but its function in apoptosis remains largely unclear because of its specific expression found within limited adult tissues. Previous overexpression studies done on various cell lines yielded conflicting conclusions pertaining to its apoptotic function. Here, we discovered the expression of endogenous Diva in PC12 neuronal-like cell line and rat bone marrow mesenchymal stem cells (BMSCs), leading to their utilisation for the functional study of Diva. Through usage of recombinant Fas ligand, hydrogen peroxide, overexpression and knock down experiments, we discovered that Diva plays a crucial pro-survival role via the mitochondrial death pathway. In addition, immunoprecipitation studies also noted a decrease in Diva's interaction with Bcl2 and Bax following apoptosis induced by oxidative stress. By overexpressing Diva in BMSCs, we had observed an increase in the cells' capacity to survive under oxidative stress and microglial toxicity. The result obtained from our study gives us reason to believe that Diva plays an important role in controlling the survival of BMSCs. Through overexpression of Diva, the viability of these BMSCs may be boosted under adverse conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Bone Marrow Cells / cytology
  • Cell Death
  • Cell Survival
  • Gene Expression Regulation*
  • Mesenchymal Stem Cells / cytology
  • Mitochondria / metabolism
  • Oxidative Stress*
  • PC12 Cells
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / physiology*
  • Rats
  • Recombinant Proteins / chemistry
  • bcl-2-Associated X Protein / metabolism

Substances

  • BCL2-like 10 protein
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Proteins
  • bcl-2-Associated X Protein

Grants and funding

This work is supported by the Singapore National Research Foundation (NRF-CRP 002-082) under its Competitive Research Programme Funding Scheme. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.