Time-dependant protective effects of mangenese(III) tetrakis (1-methyl-4-pyridyl) porphyrin on mitochondrial function following renal ischemia-reperfusion injury.
This study examined the time-dependent effects of a cell permeable SOD mimetic, MnTMPyP, on mitochondrial function in renal ischemia-reperfusion injury (IRI). Male SD rats were subject to either sham operation or bilateral renal ischemia for 45 min followed by reperfusion for 1, 4 or 24 h. A sub-set of animals was treated with either saline vehicle or 5 mg/Kg of MnTMPyP (i.p.). EPR measurements showed that at 1-h reperfusion MnTMPyP prevented a decrease in aconitase activity (p < 0.05) and attenuated the increase in the high spin heme at g = 6 and oxidation of 4Fe4S to 3Fe4S signal at g = 2.015 (p < 0.01). MnTMPyP was effective in preventing loss of mitochondrial complexes and prevented the loss of cytochrome c and Smac/Diablo from mitochondria early in reperfusion. Following 24 h of reperfusion MnTMPyP was effective in attenuating caspase-3 and blocking apoptosis (p < 0.05). In conclusion, MnTMPyP has biphasic effects in renal IRI, inhibiting mitochondrial dysfunction at the early phases of reperfusion and prevention of apoptosis following longer durations of reperfusion.
Nilakantan
Vani
V
Kidney Disease Center, Medical College of Wisconsin, 53226, USA. vnilakan@mcw.edu <vnilakan@mcw.edu>
Liang
Huan Ling
HL
Rajesh
Seenivasan
S
Mortensen
Jordan
J
Chandran
Karunakaran
K
D000154:Aconitate Hydratase / Q000032:analysis; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000032:analysis; D053148:Caspase 3 / Q000032:analysis; D045304:Cytochromes c / Q000032:analysis; D004353:Drug Evaluation, Preclinical; D004578:Electron Spin Resonance Spectroscopy; D006418:Heme / Q000032:analysis; D020287:In Situ Nick-End Labeling; D007668:Kidney / Q000098:blood supply*; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology / Q000627:therapeutic use*; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D024101:Mitochondrial Proteins / Q000032:analysis; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000032:analysis; D013997:Time Factors
D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C489013:DIABLO protein, rat; D008665:Metalloporphyrins; D024101:Mitochondrial Proteins; C502230:Mn(III) 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin; D017382:Reactive Oxygen Species; D006418:Heme; D045304:Cytochromes c; D013482:Superoxide Dismutase; C505410:Casp3 protein, rat; D053148:Caspase 3; D000154:Aconitate Hydratase