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Overexpression of mitochondrial GSH transporters in renal proximal tubular cells from control and diabetic rats
Author(s) -
Lash Lawrence Harold,
Benipal Bavneet,
Putt David Alan
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1047.1
Subject(s) - transfection , oxidative stress , chemistry , microbiology and biotechnology , streptozotocin , cytotoxicity , medicine , apoptosis , endocrinology , biochemistry , biology , diabetes mellitus , in vitro , gene
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. (Supported by DOD Grant PR64340)