Tissue kallikrein is required for the cardioprotective effect of Cyclosporin A in myocardial ischemia in the mouse

Autor: C. Richer, M.-P. Vincent, G. Youcef, François Alhenc-Gelas, Anne Pizard, Elise Belaidi, M. Clemessy, L. Fazal, Ludovic Waeckel, G. Zadigue, Michel Ovize
Přispěvatelé: Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique [Nancy] (CIC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC-Nancy, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
Rok vydání: 2015
Předmět:
Male
MESH: Signal Transduction
Myocardial Ischemia
Gene Expression
MESH: Myocytes
Cardiac
Mitochondrion
Pharmacology
MESH: Voltage-Dependent Anion Channel 1
Mitochondrial Membrane Transport Proteins
MESH: Mice
Knockout
MESH: Cyclosporine
Biochemistry
Mitochondria
Heart
Oxidative Phosphorylation
Cyclophilins
Mice
chemistry.chemical_compound
Cyclosporin a
Myocytes
Cardiac
MESH: Animals
Ischemic Postconditioning
Inner mitochondrial membrane
MESH: Heterozygote
Mice
Knockout
Cardioprotection
Tissue kallikrein
MPTP
Homozygote
MESH: Mitochondrial Membrane Transport Proteins
Mitochondria
Knockout mouse
Cyclosporine
cardiovascular system
Cardiac ischemia–reperfusion
MESH: Myocardial Ischemia
MESH: Mitochondria
Heart
Tissue Kallikreins
Cyclophilin D
Signal Transduction
MESH: Homozygote
Heterozygote
Cardiotonic Agents
MESH: Myocardium
MESH: Gene Expression
MESH: Rats
MESH: Tissue Kallikreins
Ischemia
Biology
MESH: Cyclophilins
MESH: Ischemic Postconditioning
[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
MESH: Oxidative Phosphorylation
medicine
Animals
cardiovascular diseases
MESH: Mice
Mitochondrial Permeability Transition Pore
Myocardium
Voltage-Dependent Anion Channel 1
MESH: Cardiotonic Agents
medicine.disease
MESH: Male
Rats
Cyclosporin A
Mitochondrial permeability transition pore
chemistry
Zdroj: Biochemical Pharmacology
Biochemical Pharmacology, Elsevier, 2015, 94 (1), pp.22-29. ⟨10.1016/j.bcp.2015.01.007⟩
Biochemical Pharmacology, 2015, 94 (1), pp.22-29. ⟨10.1016/j.bcp.2015.01.007⟩
ISSN: 0006-2952
1873-2968
DOI: 10.1016/j.bcp.2015.01.007
Popis: International audience; Clinical and experimental studies suggest that pharmacological postconditioning with Cyclosporin A (CsA) reduces infarct size in cardiac ischemia and reperfusion. CsA interacts with Cyclophilin D (CypD) preventing opening of the mitochondrial permeability transition pore (mPTP). Tissue kallikrein (TK) and its products kinins are involved in cardioprotection in ischemia. CypD knockout mice are resistant to the cardioprotective effects of both CsA and kinins suggesting common mechanisms of action. Using TK gene knockout mice, we investigated whether the kallikrein-kinin system is involved in the cardioprotective effect of CsA. Homozygote and heterozygote TK deficient mice (TK(-/-), TK(+/-)) and wild type littermates (TK(+/+)) were subjected to cardiac ischemia-reperfusion with and without CsA postconditioning. CsA reduced infarct size in TK(+/+) mice but had no effect in TK(+/-) and TK(-/-) mice. Cardiac mitochondria isolated from TK(-/-) mice had indistinguishable basal oxidative phosphorylation and calcium retention capacity compared to TK(+/+) mice but were resistant to CsA inhibition of mPTP opening. TK activity was documented in mouse heart and rat cardiomyoblasts mitochondria. By proximity ligation assay TK was found in close proximity to the mitochondrial membrane proteins VDAC and Tom22, and CypD. Thus, partial or total deficiency in TK induces resistance to the infarct size reducing effect of CsA in cardiac ischemia in mice, suggesting that TK level is a critical factor for cardioprotection by CsA. TK is required for the mitochondrial action of CsA and may interact with CypD. Genetic variability in TK activity has been documented in man and may influence the cardioprotective effect of CsA.
Databáze: OpenAIRE
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