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Signals regulating necrosis of cardiomyoblast by BTG2(/TIS21/PC3) via activation of GSK3β and opening of mitochondrial permeability transition pore in response to H2O2.

Authors
Choi, YW; Park, TJ; Kim, HS; Lim, IK
Citation
Biochemical and biophysical research communications, 434(3):559-565, 2013
Journal Title
Biochemical and biophysical research communications
ISSN
0006-291X1090-2104
Abstract
To investigate signal transduction pathway of cell death regulated by a tumor suppressor after oxidative stress, cardiomyoblasts were virally transfected with BTG2(/TIS21/PC3) (BTG2) and subsequently treated with H2O2. Heart muscle rarely expresses BTG2 unless oxidative stress occurs, however, ischemia induced BTG2 expression and necrosis, not apoptosis, of cardiomyoblasts. BTG2-expressioning cardiomyblasts showed impaired recoveries of survival kinases, Akt and Erk, thus sustaining GSK-3β activity in 30 min of H2O2 exposure, in contrast to their rapid recoveries in LacZ control. The phenomenon was accompanied by the failure of ATP regeneration and the sustained activation of AMPK in the BTG2 expresser. Furthermore, H2O2 treatment markedly induced BTG2 translocation from nuclei to mitochondria along with cell death by cyclophilin D activation and mPTP opening. Exogenous and endogenous effect of BTG2 was confirmed by chemical inhibitors and BTG2-KO-MEF, respectively. Here, we suggest tumor suppressor, BTG2, as one of the regulators of necrosis in myocardium via inhibiting Akt/Erk, but activating GSK3β and cyclophilin D, which resulted in mPTP opening in response to H2O2.
MeSH terms
AnimalsBase SequenceCyclophilins/metabolismDNA PrimersEnzyme ActivationGlycogen Synthase Kinase 3/*metabolismHydrogen Peroxide/*pharmacologyImmediate-Early Proteins/*metabolismImmunohistochemistryMaleMitochondrial Membrane Transport Proteins/*metabolismMyocytes, Cardiac/*metabolismNecrosisRatsRats, Sprague-DawleyReverse Transcriptase Polymerase Chain Reaction*Signal TransductionTumor Suppressor Proteins/*metabolism
DOI
10.1016/j.bbrc.2013.03.114
PMID
23583382
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
AJOU Authors
박, 태준임, 인경
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