Details

Autor(en) / Beteiligte

• Corridon, Peter
• Rhodes, George
• Zhang, Shijun
• Bready, Devin
• Xu, Weimin
• Witzmann, Frank
• Atkinson, Simon
• Basile, David
• Bacallao, Robert

Titel

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

Ist Teil von

• The FASEB journal, 2014-04, Vol.28 (S1), p.n/a

Ort / Verlag

The Federation of American Societies for Experimental Biology

Erscheinungsjahr

2014

Link zum Volltext

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• 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 following I/R injury induced by a 40 minute bilateral clamp by 82% and 74% respectively, and by 66% and 49% respectively following I/R in uninephrectomized rats. Histological analysis showed significantly reduced proximal tubule damage. We evaluated mitochondrial respiratory chain activity in vivo using 2‐photon fluorescence microscopy and the potential‐sensitive dye TMRM, and using biochemical assays in vitro, and showed that mitochondrial respiration was maintained in animals that received hydrodynamic delivery of either gene relative to controls. In conclusion, our study supports the concept that adaptive changes in mitochondria can confer protection to ischemic damage, and the utility of hydrodynamic gene delivery as a method of manipulating kidney function. Grant Funding Source: Supported by NIH/NIDDK DK088934