Interactions of GSK-3β with mitochondrial permeability transition pore modulators during preconditioning: age-associated differences.
Anesthetic preconditioning (APC) and ischemic preconditioning (IPC) are lost with normal aging. Here, we investigated age-related difference between phosphoglycogen synthase kinase-3beta (pGSK-3β) and pGSK-3β with modulators of mitochondrial permeability transition pore, including adenine nucleotide translocase (ANT), cyclophilin-D, or voltage-dependent anion channel. APC or IPC significantly increased pGSK-3β in the young groups in both the cytosol and the mitochondria and also significantly increased pGSK-3β in co-immunoprecipitates with ANT. Importantly, the level of cyclophilin-D in co-immunoprecipitates with ANT was significantly decreased in the young APC and IPC groups, but not in old rats. We also found that APC or IPC significantly prolonged mitochondrial permeability transition pore opening time in the young cardiomyocytes under oxidative stress, but not in the elderly. Attenuation of APC or IPC protection in the aging heart is associated with failure to reduce ANT-cyclophilin-D interactions and to decreased pGSK-3β responsiveness of ANT, critical modulators of mitochondrial permeability transition pore.
Department of Anesthesiology, Stony Brook University School of Medicine, HSC L4 060, NY 11794, USA.
Jiang
J
Zhu
Mario J
MJ
Rebecchi
Peter S A
PS
Glass
Peter R
PR
Brink
Lixin
L
Liu
D000367:Age Factors; D000818:Animals; D016922:Cellular Senescence; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D047468:Immunoprecipitation; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D023421:Models, Animal; D032383:Myocytes, Cardiac / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D011916:Rats, Inbred F344; D050994:Voltage-Dependent Anion Channels / Q000378:metabolism*
D000081406:Peptidyl-Prolyl Isomerase F; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D050994:Voltage-Dependent Anion Channels; D000226:Mitochondrial ADP, ATP Translocases; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; D021983:Cyclophilins