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...

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Published in:The journals of gerontology. Series A, Biological sciences and medical sciences Biological sciences and medical sciences, 2013-04, Vol.68 (4), p.395-403
Main Authors: Zhu, Jiang, Rebecchi, Mario J, Glass, Peter S A, Brink, Peter R, Liu, Lixin
Format: Article
Language:English
Subjects:
Age Factors
Animals
Cellular Senescence
Cyclophilins - metabolism
Glycogen Synthase Kinase 3 - metabolism
Glycogen Synthase Kinase 3 beta
Immunoprecipitation
Ischemic Preconditioning, Myocardial - methods
Male
Mitochondria, Heart - metabolism
Mitochondrial ADP, ATP Translocases - metabolism
Mitochondrial Membrane Transport Proteins - metabolism
Mitochondrial Permeability Transition Pore
Models, Animal
Myocytes, Cardiac - metabolism
Oxidative Stress
Peptidyl-Prolyl Isomerase F
Rats
Rats, Inbred F344
Voltage-Dependent Anion Channels - metabolism
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Summary: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.
ISSN:1758-535X
DOI:10.1093/gerona/gls205