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

• DOI: 10.3181/0810-rm-312
• Publication Date: 2009-02-26T02:50:24Z
• Authors: Keith R. Brunt; Matthew R. Tsuji; Joyce H. Lai; Robert T. Kinobe; William Durante; William C. Claycomb; Christopher A. Ward; Luis G. Melo
• Keywords: 0303 health sciences; NF-kappa B; Cardiomegaly; Hydrogen Peroxide; Oxidants; Adenoviridae; Cell Line; Rats; 03 medical and health sciences; Transduction, Genetic; Heme Oxygenase (Decyclizing); Animals; Myocytes, Cardiac; Oxidation-Reduction

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