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Carvedilol inhibits mitochondrial complex I and induces resistance to H2O2 -mediated oxidative insult in H9C2 myocardial cells.
Biochim Biophys Acta 2007; 1767(3):222-32BB

Abstract

Carvedilol, a beta-adrenoreceptor antagonist with strong antioxidant activity, produces a high degree of cardioprotection in a variety of experimental models of ischemic cardiac injury. Although growing evidences suggest specific effects on mitochondrial metabolism, how carvedilol would exert its overall activity has not been completely disclosed. In the present work we have investigated the impact of carvedilol-treatment on mitochondrial bioenergetic functions and ROS metabolism in H9C2 cells. This analysis has revealed a dose-dependent decrease in respiratory fluxes by NAD-dependent substrates associated with a consistent decline of mitochondrial complex I activity. These changes were associated with an increase in mitochondrial H(2)O(2) production, total glutathione and protein thiols content. To evaluate the antioxidant activity of carvedilol, the effect of the exposure of control and carvedilol-pretreated H9C2 cells to H(2)O(2) were investigated. The H(2)O(2)-mediated oxidative insult resulted in a significant decrease of mitochondrial respiration, glutathione and protein thiol content and in an increased level of GSSG. These changes were prevented by carvedilol-pretreatment. A similar protective effect on mitochondrial respiration could be obtained by pre-treatment of the cells with a sub-saturating amount of rotenone, a complex I inhibitor. We therefore suggest that carvedilol exerts its protective antioxidant action both by a direct antioxidant effect and by a preconditioning-like mechanism, via inhibition of mitochondrial complex I.

Authors+Show Affiliations

Department of Medical Biochemistry, Biology and Physics, University of Bari, 70124 Bari, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17346667

Citation

Sgobbo, Paola, et al. "Carvedilol Inhibits Mitochondrial Complex I and Induces Resistance to H2O2 -mediated Oxidative Insult in H9C2 Myocardial Cells." Biochimica Et Biophysica Acta, vol. 1767, no. 3, 2007, pp. 222-32.
Sgobbo P, Pacelli C, Grattagliano I, et al. Carvedilol inhibits mitochondrial complex I and induces resistance to H2O2 -mediated oxidative insult in H9C2 myocardial cells. Biochim Biophys Acta. 2007;1767(3):222-32.
Sgobbo, P., Pacelli, C., Grattagliano, I., Villani, G., & Cocco, T. (2007). Carvedilol inhibits mitochondrial complex I and induces resistance to H2O2 -mediated oxidative insult in H9C2 myocardial cells. Biochimica Et Biophysica Acta, 1767(3), pp. 222-32.
Sgobbo P, et al. Carvedilol Inhibits Mitochondrial Complex I and Induces Resistance to H2O2 -mediated Oxidative Insult in H9C2 Myocardial Cells. Biochim Biophys Acta. 2007;1767(3):222-32. PubMed PMID: 17346667.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Carvedilol inhibits mitochondrial complex I and induces resistance to H2O2 -mediated oxidative insult in H9C2 myocardial cells. AU - Sgobbo,Paola, AU - Pacelli,Consiglia, AU - Grattagliano,Ignazio, AU - Villani,Gaetano, AU - Cocco,Tiziana, Y1 - 2007/02/09/ PY - 2006/09/25/received PY - 2007/01/29/revised PY - 2007/01/31/accepted PY - 2007/3/10/pubmed PY - 2007/5/5/medline PY - 2007/3/10/entrez SP - 222 EP - 32 JF - Biochimica et biophysica acta JO - Biochim. Biophys. Acta VL - 1767 IS - 3 N2 - Carvedilol, a beta-adrenoreceptor antagonist with strong antioxidant activity, produces a high degree of cardioprotection in a variety of experimental models of ischemic cardiac injury. Although growing evidences suggest specific effects on mitochondrial metabolism, how carvedilol would exert its overall activity has not been completely disclosed. In the present work we have investigated the impact of carvedilol-treatment on mitochondrial bioenergetic functions and ROS metabolism in H9C2 cells. This analysis has revealed a dose-dependent decrease in respiratory fluxes by NAD-dependent substrates associated with a consistent decline of mitochondrial complex I activity. These changes were associated with an increase in mitochondrial H(2)O(2) production, total glutathione and protein thiols content. To evaluate the antioxidant activity of carvedilol, the effect of the exposure of control and carvedilol-pretreated H9C2 cells to H(2)O(2) were investigated. The H(2)O(2)-mediated oxidative insult resulted in a significant decrease of mitochondrial respiration, glutathione and protein thiol content and in an increased level of GSSG. These changes were prevented by carvedilol-pretreatment. A similar protective effect on mitochondrial respiration could be obtained by pre-treatment of the cells with a sub-saturating amount of rotenone, a complex I inhibitor. We therefore suggest that carvedilol exerts its protective antioxidant action both by a direct antioxidant effect and by a preconditioning-like mechanism, via inhibition of mitochondrial complex I. SN - 0006-3002 UR - https://www.unboundmedicine.com/medline/citation/17346667/Carvedilol_inhibits_mitochondrial_complex_I_and_induces_resistance_to_H2O2__mediated_oxidative_insult_in_H9C2_myocardial_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0005-2728(07)00026-6 DB - PRIME DP - Unbound Medicine ER -