Overexpression of mitochondrial GSH transporters in renal proximal tubular cells from control and diabetic rats
Abstract
We hypothesize that overexpression of mitochondrial glutathione (mtGSH) transporters in renal proximal tubular (PT) cells from diabetic rats will reverse the oxidative stress and diminish susceptibility to chemically induced cytotoxicity by producing sustained increases in mtGSH content. cDNAs encoding either the dicarboxylate (DIC; Slc25a10) or 2‐oxoglutarate (OGC; Slc25a11) carrier were expressed in renal PT cells from either control or streptozotocin‐induced diabetic Sprague‐Dawley rats using Lipofectamine. Transfection with either DIC or OGC cDNA produced 7,800‐ or 5,000‐fold increases in DIC or OGC mRNA, respectively, in cells from control rats and 600‐ and 1900‐fold increases in DIC or OGC mRNA, respectively, in cells from diabetic rats. Carrier overexpression provided significant protection, as judged by LDH release and MTT fluorescence, from injury due to the mitochondrial toxicant antimycin A. These results suggest that mtGSH carrier overexpression may be a viable approach to improving redox status of renal cells in chronic disease states.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2012
- Source ID
- 10.1096/fasebj.26.1_supplement.1047.1
Entities
People
- Bavneet Benipal
- David Alan Putt
- Lawrence Harold Lash
Organizations
- United States Department of Defense