Heme Oxygenase-1 Inhibits Pro-Oxidant Induced Hypertrophy in HL-1 Cardiomyocytes

Experimental Biology and Medicine - Tập 234 Số 5 - Trang 582-594 - 2009
Keith R. Brunt1,2,3, Matthew R. Tsuji1,2,3, Joyce Lai1,2,3, Robert T. Kinobe1,2,3, William Durante1,2,3, William C. Claycomb1,2,3, Christopher A. Ward1,2,3, Luis G. Melo1,2,3
1Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, Missouri 65212
2Department of Physiology, Queen's University, Kingston, Ontario, K7L 3N6 Canada
3Department of Physiology, Queen’s University, Kingston, Ontario, K7L 3N6 Canada; Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, Missouri 65212; and Department of Biochemistry and Molecular Biology, Louisiana State University, Health Sciences Center, New Orleans, Louisiana 70112-1394

Tóm tắt

Aims: Reactive oxygen species (ROS) activate multiple signaling pathways involved in cardiac hypertrophy. Since HO-1 exerts potent antioxidant effects, we hypothesized that this enzyme inhibits ROS-induced cardiomyocyte hypertrophy. Methods: HL-1 cardiomyocytes were transduced with an adenovirus constitutively expressing HO-1 (AdHO-1) to increase basal HO-1 expression and then exposed to 200 μM hydrogen peroxide (H2O2). Hypertrophy was measured using 3H-leucine incorporation, planar morphometry and cell-size by forward-scatter flow-cytometry. The pro-oxidant effect of H2O2 was assessed by redox sensitive fluorophores. Inducing intracellular redox imbalance resulted in cardiomyocyte hypertrophy through transactivation of nuclear factor kappa B (NF-κB). Results: Pre-emptive HO-1 overexpression attenuated the redox imbalance and reduced hypertrophic indices. This is the first time that HO-1 has directly been shown to inhibit oxidant-induced cardiomyocyte hypertrophy by a NF-κB–dependent mechanism. Conclusion: These results demonstrate that HO-1 inhibits pro-oxidant induced cardiomyocyte hypertrophy and suggest that HO-1 may yield therapeutic potential in treatment of

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Experimental Biology and Medicine

Tập 234 Số 5

582-594

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