Heme oxygenase-1 inhibits pro-oxidant induced hypertrophy in HL-1 cardiomyocytes

Keith R. Brunt; Matthew R. Tsuji; Joyce H. Lai; Robert T. Kinobe; William Durante; William C. Claycomb; Christopher A. Ward; Luis G. Melo

doi:10.3181/0810-RM-312

Heme oxygenase-1 inhibits pro-oxidant induced hypertrophy in HL-1 cardiomyocytes

Keith R. Brunt, Matthew R. Tsuji, Joyce H. Lai, Robert T. Kinobe, William Durante, William C. Claycomb, Christopher A. Ward, Luis G. Melo

Research output: Contribution to journal › Article › peer-review

31 Citations (Scopus)

Abstract

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 H ₂O₂ 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.

Original language	English
Pages (from-to)	582-594
Number of pages	13
Journal	Experimental Biology and Medicine
Volume	234
Issue number	5
DOIs	https://doi.org/10.3181/0810-RM-312
Publication status	Published - May 2009
Externally published	Yes

Bibliographical note

Funding Information:
This work was supported by grants from the Canadian Institutes of Health Research (CIHR, MOP 79506) and the Heart and Stroke Foundation of Ontario (HSFO, NA 5779) to L. G. M. and C. A. W. W. D. is supported by a grant from the National Institute of Health (NIH, HL59976). K. R. B. is supported by a doctoral award from Canadian Institute of Health Research/Heart & Stroke Foundation G.R.E.A.T. training program. R. K. is supported by a postdoctoral fellowship from the Heart and Stroke Foundation of Canada. L. G. M. was a Canada Research Chair in Molecular Cardiology and a New Investigator of the Heart and Stroke Foundation of Canada.

ASJC Scopus Subject Areas

General Biochemistry,Genetics and Molecular Biology

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@article{b6883fe9afe34cf7b11a83ad29a1cec5,

title = "Heme oxygenase-1 inhibits pro-oxidant induced hypertrophy in HL-1 cardiomyocytes",

abstract = "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 H 2O2 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.",

author = "Brunt, {Keith R.} and Tsuji, {Matthew R.} and Lai, {Joyce H.} and Kinobe, {Robert T.} and William Durante and Claycomb, {William C.} and Ward, {Christopher A.} and Melo, {Luis G.}",

note = "Funding Information: This work was supported by grants from the Canadian Institutes of Health Research (CIHR, MOP 79506) and the Heart and Stroke Foundation of Ontario (HSFO, NA 5779) to L. G. M. and C. A. W. W. D. is supported by a grant from the National Institute of Health (NIH, HL59976). K. R. B. is supported by a doctoral award from Canadian Institute of Health Research/Heart & Stroke Foundation G.R.E.A.T. training program. R. K. is supported by a postdoctoral fellowship from the Heart and Stroke Foundation of Canada. L. G. M. was a Canada Research Chair in Molecular Cardiology and a New Investigator of the Heart and Stroke Foundation of Canada.",

year = "2009",

month = may,

doi = "10.3181/0810-RM-312",

language = "English",

volume = "234",

pages = "582--594",

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T1 - Heme oxygenase-1 inhibits pro-oxidant induced hypertrophy in HL-1 cardiomyocytes

AU - Brunt, Keith R.

AU - Tsuji, Matthew R.

AU - Lai, Joyce H.

AU - Kinobe, Robert T.

AU - Durante, William

AU - Claycomb, William C.

AU - Ward, Christopher A.

AU - Melo, Luis G.

N1 - Funding Information: This work was supported by grants from the Canadian Institutes of Health Research (CIHR, MOP 79506) and the Heart and Stroke Foundation of Ontario (HSFO, NA 5779) to L. G. M. and C. A. W. W. D. is supported by a grant from the National Institute of Health (NIH, HL59976). K. R. B. is supported by a doctoral award from Canadian Institute of Health Research/Heart & Stroke Foundation G.R.E.A.T. training program. R. K. is supported by a postdoctoral fellowship from the Heart and Stroke Foundation of Canada. L. G. M. was a Canada Research Chair in Molecular Cardiology and a New Investigator of the Heart and Stroke Foundation of Canada.

PY - 2009/5

Y1 - 2009/5

N2 - 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 H 2O2 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.

AB - 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 H 2O2 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.

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Heme oxygenase-1 inhibits pro-oxidant induced hypertrophy in HL-1 cardiomyocytes

Abstract

Bibliographical note

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