Gomez 2008 Circulation: Difference between revisions
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{{Publication | {{Publication | ||
|title=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. | |title=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. | ||
|authors=Gomez L, Paillard M, Thibault H, Derumeaux G, Ovize M | |authors=Gomez L, Paillard M, Thibault H, Derumeaux G, Ovize M | ||
|year=2008 | |year=2008 | ||
|journal=Circulation | |journal=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=Ischemia, Myocardial infarction, Reperfusion | |||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/18490522 PMID: 18490522] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/18490522 PMID: 18490522] | ||
}} | }} | ||
{{Labeling | {{Labeling | ||
| | |discipline=Biomedicine | ||
|injuries=Ischemia-Reperfusion; Preservation, Genetic Defect; Knockdown; Overexpression | |||
|organism=Mouse | |||
|tissues=Cardiac Muscle | |||
|preparations=Permeabilized Cell or Tissue; Homogenate | |||
|topics=Respiration; OXPHOS; ETS Capacity | |topics=Respiration; OXPHOS; ETS Capacity | ||
|instruments=Oxygraph-2k, Spectrophotometry; Spectrofluorimetry, Chemicals; Media, Method | |||
|articletype=Protocol; Manual | |||
}} | }} | ||
Revision as of 15:13, 29 September 2010
| 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. |
» [[Has info::PMID: 18490522]]
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: Ischemia, Myocardial infarction, Reperfusion
Labels:
Stress:Ischemia-Reperfusion; Preservation, Genetic Defect; Knockdown; Overexpression Organism: Mouse Tissue;cell: Cardiac Muscle Preparation: Permeabilized Cell or Tissue; Homogenate
Regulation: Respiration; OXPHOS; ETS Capacity
HRR: Oxygraph-2k, Spectrophotometry; Spectrofluorimetry, Chemicals; Media, Method
