Difference between revisions of "Gomez 2008 Circulation"
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'''Conclusion'''—These results suggest that S9-phosphorylation of GSK3β is required for postconditioning and likely acts by inhibiting the opening of the mitochondrial permeability transition pore. | '''Conclusion'''—These results suggest that S9-phosphorylation of GSK3β is required for postconditioning and likely acts by inhibiting the opening of the mitochondrial permeability transition pore. | ||
|keywords= | |keywords=Myocardial infarction | ||
|discipline=Biomedicine | |discipline=Biomedicine | ||
}} | }} | ||
{{Labeling | {{Labeling | ||
| | |area=Pharmacology;toxicology | ||
|organism=Mouse | |organism=Mouse | ||
|tissues=Heart | |tissues=Heart | ||
|preparations=Isolated Mitochondria | |preparations=Isolated Mitochondria | ||
|injuries=Ischemia-Reperfusion; Preservation, Permeability transition | |||
|couplingstates=OXPHOS | |couplingstates=OXPHOS | ||
|instruments=Oxygraph-2k | |||
|additional=Spectrophotometry; Spectrofluorimetry | |additional=Spectrophotometry; Spectrofluorimetry | ||
|discipline=Biomedicine | |discipline=Biomedicine | ||
}} | }} |
Revision as of 23:57, 11 August 2013
Gomez L, Paillard M, Thibault H, Derumeaux G, Ovize M (2008) Inhibition of GSK3beta by postconditioning is required to prevent opening of the mitochondrial permeability transition pore during reperfusion. Circulation 117: 2761-2768. |
Gomez L, Paillard M, Thibault H, Derumeaux G, Ovize M (2008) Circulation
Abstract: Background—Opening of the mitochondrial permeability transition pore (mPTP) is a crucial event in lethal reperfusion injury. Phosphorylation (inhibition) of glycogen synthase kinase-3β (GSK3β) has been involved in cardioprotection. We investigated whether phosphorylated GSK3β may protect the heart via the inhibition of mPTP opening during postconditioning.
Methods and Results—Wild-type and transgenic GSK3β-S9A mice (the cardiac GSK3β activity of which cannot be inactivated) underwent 60 minutes of ischemia and 24 hours of reperfusion. At reperfusion, wild-type and GSK3β-S9A mice received no intervention (control), postconditioning (3 cycles of 1 minute ischemia and 1 minute of reperfusion), the mPTP inhibitor cyclosporine A (CsA; 10 mg/kg IV), or the GSK3β inhibitor SB216763 (SB21; 70 µg/kg IV). Infarct size was assessed by triphenyltetrazolium chloride staining. The resistance of the mPTP to opening after Ca2+ loading was assessed by spectrofluorometry on mitochondria isolated from the area at risk. In wild-type mice, infarct size was significantly reduced by postconditioning, CsA, and SB21, averaging 39±2%, 35±5%, and 37±4%, respectively, versus 58±5% of the area at risk in control mice (P<0.05). In GSK3β-S9A mice, only CsA, but not postconditioning or SB21, reduced infarct size. Postconditioning, CsA, and SB21 all improved the resistance of the mPTP in wild-type mice, but only CsA did so in GSK3β-S9A mice.
Conclusion—These results suggest that S9-phosphorylation of GSK3β is required for postconditioning and likely acts by inhibiting the opening of the mitochondrial permeability transition pore. • Keywords: Myocardial infarction
Labels: MiParea: Pharmacology;toxicology
Stress:Ischemia-Reperfusion; Preservation"Ischemia-Reperfusion; Preservation" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property., Permeability transition Organism: Mouse Tissue;cell: Heart Preparation: Isolated Mitochondria"Isolated Mitochondria" is not in the list (Intact organism, Intact organ, Permeabilized cells, Permeabilized tissue, Homogenate, Isolated mitochondria, SMP, Chloroplasts, Enzyme, Oxidase;biochemical oxidation, ...) of allowed values for the "Preparation" property.
Coupling state: OXPHOS
HRR: Oxygraph-2k
Spectrophotometry; Spectrofluorimetry