Kolb 2018 J Am Soc Nephrol

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Kolb AL, Corridon PR, Zhang S, Xu W, Witzmann FA, Collett JA, Rhodes GJ, Winfree S, Bready D, Pfeffenberger ZJ, Pomerantz JM, Hato T, Nagami GT, Molitoris BA, Basile DP, Atkinson SJ, Bacallao RL (2018) Exogenous gene transmission of isocitrate dehydrogenase 2 mimics ischemic preconditioning protection. J Am Soc Nephrol 29:1154-64.

» PMID: 29371417

Kolb AL, Corridon PR, Zhang S, Xu W, Witzmann FA, Collett JA, Rhodes GJ, Winfree S, Bready D, Pfeffenberger ZJ, Pomerantz JM, Hato T, Nagami GT, Molitoris BA, Basile DP, Atkinson SJ, Bacallao RL (2018) J Am Soc Nephrol

Abstract: Ischemic preconditioning confers organ-wide protection against subsequent ischemic stress. A substantial body of evidence underscores the importance of mitochondria adaptation as a critical component of cell protection from ischemia. To identify changes in mitochondria protein expression in response to ischemic preconditioning, we isolated mitochondria from ischemic preconditioned kidneys and sham-treated kidneys as a basis for comparison. The proteomic screen identified highly upregulated proteins, including NADP+-dependent isocitrate dehydrogenase 2 (IDH2), and we confirmed the ability of this protein to confer cellular protection from injury in murine S3 proximal tubule cells subjected to hypoxia. To further evaluate the role of IDH2 in cell protection, we performed detailed analysis of the effects of Idh2 gene delivery on kidney susceptibility to ischemia-reperfusion injury. Gene delivery of IDH2 before injury attenuated the injury-induced rise in serum creatinine (P<0.05) observed in controls and increased the mitochondria membrane potential (P<0.05), maximal respiratory capacity (P<0.05), and intracellular ATP levels (P<0.05) above those in controls. This communication shows that gene delivery of Idh2 can confer organ-wide protection against subsequent ischemia-reperfusion injury and mimics ischemic preconditioning.

Keywords: Acute renal failure, Ischemic preconditioning, Retrograde renal vein injection Bioblast editor: Kandolf G


Labels: MiParea: Respiration 

Stress:Ischemia-reperfusion 

Tissue;cell: Kidney  Preparation: Isolated mitochondria 


Coupling state: OXPHOS  Pathway: N, NS  HRR: Oxygraph-2k 

Labels, 2018-07