Heme oxygenase-1 inhibits pro-oxidant induced hypertrophy in HL-1 cardiomyocytes.
OBJECTIVE
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 microM 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-kappaB).


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-kappaB-dependent mechanism.


CONCLUSIONS
These results demonstrate that HO-1 inhibits pro-oxidant induced cardiomyocyte hypertrophy and suggest that HO-1 may yield therapeutic potential in treatment of.
Brunt
Keith R
KR
Department of Physiology, Queen's University, 431 Botterell Hall, Kingston, Ontario K7L 3N6, Canada.
Tsuji
Matthew R
MR
Lai
Joyce H
JH
Kinobe
Robert T
RT
Durante
William
W
Claycomb
William C
WC
Ward
Christopher A
CA
Melo
Luis G
LG
D000256:Adenoviridae; D000818:Animals; D006332:Cardiomegaly / Q000201:enzymology* / Q000235:genetics / Q000628:therapy; D002460:Cell Line; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000201:enzymology*; D016328:NF-kappa B / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology*; D010084:Oxidation-Reduction; D051381:Rats; D014161:Transduction, Genetic
D016328:NF-kappa B; D016877:Oxidants; D006861:Hydrogen Peroxide; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat