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PI 3-kinase regulates the mitochondrial transition pore in controlled reperfusion and postconditioning.
Cardiovasc Res. 2006 Jan; 69(1):178-85.CR

Abstract

OBJECTIVE

We investigated whether phosphatidylinositol 3-kinase (PI3K) might regulate mitochondrial permeability transition pore (mPTP) opening in hearts reperfused with either low pressure or postconditioning.

METHODS

Male Wistar rat hearts (n=72) were perfused according to the Langendorff technique, exposed to 30 min of ischemia, and assigned to one of the following groups: (1) reperfusion with normal pressure (NP; 100 cm H2O), (2) reperfusion with low pressure (LP; 70 cm H2O), or reperfusion with postconditioning, i.e. 3 episodes of 30 s reperfusion followed by 30 s of ischemia (PostC). Hearts received either the PI3K inhibitors wortmannin or LY294002, or vehicle at the onset of the 60 min reperfusion. Postischemic functional recovery was assessed by rate-pressure product (RPP), and irreversible injury by lactate dehydrogenase (LDH), creatine kinase (CK) and troponin I (TnI) release. Mitochondria were isolated from the reperfused myocardium, and Ca2+-induced mPTP opening was measured using a potentiometric method.

RESULTS

Functional recovery was significantly improved in LP and PostC hearts with RPP averaging 13,880+/-810 (LP) and 17,130+/-900 mm Hgxbeats/min (PostC) versus 6450+/-500 mm Hgxbeats/min in NP hearts (p<0.01). LDH release averaged 230+/-30 and 145+/-15 IU/h/g of myocardial tissue in LP and PostC versus 340+/-10 IU/h/g in NP (p<0.05). Wortmannin and LY294002 prevented both RPP improvement and decrease in LDH, CK, and TnI release in LP and PostC groups. The Ca2+ load required to induce mPTP opening averaged 58+/-3 and 52+/-1 nmol/mg mitochondrial proteins in LP and PostC groups, respectively, versus 35+/-4 nmol/mg in the NP group (p<0.01). Wortmannin and LY294002 prevented the beneficial effect in both the LP and PostC groups.

CONCLUSION

These results suggest that PI3K regulates the opening of the mitochondrial permeability transition pore in rat hearts reperfused with low pressure or postconditioning.

Authors+Show Affiliations

Bopassa JC
INSERM E0226, Université Claude Bernard Lyon I, Laboratoire de Physiologie Lyon-Nord 8, avenue Rockefeller, 69373 LYON Cedex 08, France.
Ferrera R
No affiliation info available
Gateau-Roesch O
No affiliation info available
Couture-Lepetit E
No affiliation info available
Ovize M
No affiliation info available

MeSH

AnimalsBlotting, WesternCalciumCoronary DiseaseIon ChannelsIschemic Preconditioning, MyocardialMaleMitochondrial Membrane Transport ProteinsMitochondrial Permeability Transition PoreMyocardial ReperfusionMyocardial Reperfusion InjuryMyocardiumNecrosisPhosphatidylinositol 3-KinasesRandom AllocationRatsRats, WistarVentricular Function, Left

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16216231

Citation

Bopassa, Jean-Chrisostome, et al. "PI 3-kinase Regulates the Mitochondrial Transition Pore in Controlled Reperfusion and Postconditioning." Cardiovascular Research, vol. 69, no. 1, 2006, pp. 178-85.
Bopassa JC, Ferrera R, Gateau-Roesch O, et al. PI 3-kinase regulates the mitochondrial transition pore in controlled reperfusion and postconditioning. Cardiovasc Res. 2006;69(1):178-85.
Bopassa, J. C., Ferrera, R., Gateau-Roesch, O., Couture-Lepetit, E., & Ovize, M. (2006). PI 3-kinase regulates the mitochondrial transition pore in controlled reperfusion and postconditioning. Cardiovascular Research, 69(1), 178-85.
Bopassa JC, et al. PI 3-kinase Regulates the Mitochondrial Transition Pore in Controlled Reperfusion and Postconditioning. Cardiovasc Res. 2006;69(1):178-85. PubMed PMID: 16216231.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PI 3-kinase regulates the mitochondrial transition pore in controlled reperfusion and postconditioning. AU - Bopassa,Jean-Chrisostome, AU - Ferrera,René, AU - Gateau-Roesch,Odile, AU - Couture-Lepetit,Elisabeth, AU - Ovize,Michel, Y1 - 2005/10/07/ PY - 2005/02/16/received PY - 2005/07/13/revised PY - 2005/07/15/accepted PY - 2005/10/12/pubmed PY - 2006/5/4/medline PY - 2005/10/12/entrez SP - 178 EP - 85 JF - Cardiovascular research JO - Cardiovasc Res VL - 69 IS - 1 N2 - OBJECTIVE: We investigated whether phosphatidylinositol 3-kinase (PI3K) might regulate mitochondrial permeability transition pore (mPTP) opening in hearts reperfused with either low pressure or postconditioning. METHODS: Male Wistar rat hearts (n=72) were perfused according to the Langendorff technique, exposed to 30 min of ischemia, and assigned to one of the following groups: (1) reperfusion with normal pressure (NP; 100 cm H2O), (2) reperfusion with low pressure (LP; 70 cm H2O), or reperfusion with postconditioning, i.e. 3 episodes of 30 s reperfusion followed by 30 s of ischemia (PostC). Hearts received either the PI3K inhibitors wortmannin or LY294002, or vehicle at the onset of the 60 min reperfusion. Postischemic functional recovery was assessed by rate-pressure product (RPP), and irreversible injury by lactate dehydrogenase (LDH), creatine kinase (CK) and troponin I (TnI) release. Mitochondria were isolated from the reperfused myocardium, and Ca2+-induced mPTP opening was measured using a potentiometric method. RESULTS: Functional recovery was significantly improved in LP and PostC hearts with RPP averaging 13,880+/-810 (LP) and 17,130+/-900 mm Hgxbeats/min (PostC) versus 6450+/-500 mm Hgxbeats/min in NP hearts (p<0.01). LDH release averaged 230+/-30 and 145+/-15 IU/h/g of myocardial tissue in LP and PostC versus 340+/-10 IU/h/g in NP (p<0.05). Wortmannin and LY294002 prevented both RPP improvement and decrease in LDH, CK, and TnI release in LP and PostC groups. The Ca2+ load required to induce mPTP opening averaged 58+/-3 and 52+/-1 nmol/mg mitochondrial proteins in LP and PostC groups, respectively, versus 35+/-4 nmol/mg in the NP group (p<0.01). Wortmannin and LY294002 prevented the beneficial effect in both the LP and PostC groups. CONCLUSION: These results suggest that PI3K regulates the opening of the mitochondrial permeability transition pore in rat hearts reperfused with low pressure or postconditioning. SN - 0008-6363 UR - https://www.unboundmedicine.com/medline/citation/16216231/PI_3_kinase_regulates_the_mitochondrial_transition_pore_in_controlled_reperfusion_and_postconditioning_ DB - PRIME DP - Unbound Medicine ER -