Heme oxygenase-1 inhibits pro-oxidant induced hypertrophy in HL-1 cardiomyocytes
Brunt, Keith R., Tsuji, Mathew R., Lai, Joyce H., Kinobe, Robert T., Durante, William, Claycomb, William C., Ward, Christopher A., and Melo, Luis G. (2009) Heme oxygenase-1 inhibits pro-oxidant induced hypertrophy in HL-1 cardiomyocytes. Experimental Biology and Medicine, 234 (5). pp. 582-594.
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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 cardiac hypertrophy and prevention of heart failure.
|Item Type:||Article (Refereed Research - C1)|
|Keywords:||NF-jB; adenovirus; heme; carbon monoxide; bilirubin; oxidative stress|
|Funders:||Canadian Institue of Health Research and The Heart & Stroke Foundation of Canada|
|Date Deposited:||20 Aug 2012 03:47|
|FoR Codes:||11 MEDICAL AND HEALTH SCIENCES > 1116 Medical Physiology > 111601 Cell Physiology @ 60%
11 MEDICAL AND HEALTH SCIENCES > 1115 Pharmacology and Pharmaceutical Sciences > 111501 Basic Pharmacology @ 40%
|SEO Codes:||92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 100%|