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Glutathione peroxidase deficiency exacerbates ischemia-reperfusion injury in male but not female myocardium : insights into antioxidant compensatory mechanisms
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Lim, Chee Chew, Bryan, Nathan S., Jain, Mohit, Garcia-Saura, Maria F., Fernandez, Bernadette O., Sawyer, Douglas B., Handy, Diane E., Loscalzo, Joseph, Feelisch, Martin and Liao, Ronglih (2009) Glutathione peroxidase deficiency exacerbates ischemia-reperfusion injury in male but not female myocardium : insights into antioxidant compensatory mechanisms. AJP : Heart and Circulatory Physiology, Vol.297 (No.6). H2144-53. doi:10.1152/ajpheart.00673.2009 ISSN 1522-1539.
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Official URL: http://dx.doi.org/10.1152/ajpheart.00673.2009
Abstract
The female sex has been associated with increased resistance to acute myocardial ischemia-reperfusion (I/R) injury. While enhanced antioxidant capacity has been implicated in female cardioprotection, there is little evidence to support this assumption. Previous studies have shown an important role of cellular glutathione peroxidase (GPx1) in protection of the myocardium from I/R injury. Whether GPx1 is mechanistic in the protection of female myocardium, post-I/R, has not been examined. We utilized a murine model with homozygous deletion of GPx1 and examined its impact on postischemic myocardial recovery in male and female mice. Following I/R, male GPx1(-/-) hearts were more susceptible to contractile and diastolic dysfunction, and this was associated with increased protein carbonyls, a marker of oxidative stress. In contrast, GPx1 deficiency in female hearts did not exacerbate dysfunction or oxidative stress post-I/R. Both wild-type and GPx1(-/-) female hearts exhibited reduced creatine kinase leakage and a more favorable ascorbate redox status compared with males. Following I/R, female GPx1(-/-) hearts showed a comparable decrease in glutathione redox status as their male counterparts; however, they exhibited a greater decrease in nitrate-to-nitrite ratio, suggesting a higher consumption of nitrate in female GPx1(-/-) hearts. Our findings demonstrate that GPx1 is critical for cardioprotection during I/R in male, but not female, mice. The maintenance of cardioprotection in female mice lacking GPx1 post-I/R may be due to an improved ascorbate redox homeostasis and enhanced nitrate-to-nitrite conversion, which would predictably be accompanied by enhanced production of cardioprotective nitric oxide.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Subjects: | R Medicine > R Medicine (General) | ||||
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Journal or Publication Title: | AJP : Heart and Circulatory Physiology | ||||
| Publisher: | American Physiological Society | ||||
| ISSN: | 1522-1539 | ||||
| Official Date: | December 2009 | ||||
| Dates: |
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| Volume: | Vol.297 | ||||
| Number: | No.6 | ||||
| Page Range: | H2144-53 | ||||
| DOI: | 10.1152/ajpheart.00673.2009 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access |
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