Hydrodynamic delivery of mitochondrial genes in vivo protects against moderate ischemia‐reperfusion injury in the rat kidney (690.17)

Ischemic preconditioning is well known to afford protection against subsequent episodes of ischemia/reperfusion (I/R) in multiple organs, including the kidney, but the mechanisms involved are not fully understood. We proposed that ischemic preconditioning results in an altered mitochondrial proteome that confers resistance to subsequent I/R injury. We subjected rats to moderate ischemic injury and used liquid chromatography – mass spectroscopy (LC/MS) to analyze the proteome of kidney cortical mitochondria isolated following 14 days of recovery from I/R. The expression of several proteins was elevated following preconditioning, and two were selected for further analysis: Isocitrate dehydrogenase 2 (IDH2) and a member of the sulfotransferase family (SULT1A1). The effect of increased expression of these proteins was evaluated by using hydrodynamic gene delivery of plasmid vectors to overexpress each protein. Strikingly, hydrodynamic delivery of IDH2 and SULT1A1 genes attenuated the peak in serum creatinine ...