The University of Southampton
University of Southampton Institutional Repository

Glutathione peroxidase deficiency exacerbates ischemia-reperfusion injury in male but not female myocardium: insights into antioxidant compensatory mechanisms

Glutathione peroxidase deficiency exacerbates ischemia-reperfusion injury in male but not female myocardium: insights into antioxidant compensatory mechanisms
Glutathione peroxidase deficiency exacerbates ischemia-reperfusion injury in male but not female myocardium: insights into antioxidant compensatory mechanisms
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.
ischemia, reperfusion, gender, free radicals, antioxidants, ascorbate, nitric oxide, nitrite
0363-6135
H2144-H2153
Lim, Chee Chew
65fe4f16-8f1c-4d78-89d0-dfc4461bd4d9
Bryan, Nathan S.
709ff51c-c864-4862-9e3f-c5cfd3961025
Jain, Mohit
b068a610-75df-4624-b92f-6035714012ac
Garcia-Saura, Maria F.
a3df7c56-91cf-476d-8de8-ce31a42c13e4
Fernandez, Bernadette O.
27babc73-7646-4908-86e2-6c29d79fb938
Sawyer, Douglas B.
19e717d5-0a6f-4a01-aff5-fabc03016d89
Handy, Diane E.
65724761-f537-44fa-a42c-3999b47726dc
Loscalzo, Joseph
693bbc82-3c0e-4209-b7f6-5c8632fb4257
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Liao, Ronglih
a5f01676-e70d-41a6-95f8-4fcbd177cd16
Lim, Chee Chew
65fe4f16-8f1c-4d78-89d0-dfc4461bd4d9
Bryan, Nathan S.
709ff51c-c864-4862-9e3f-c5cfd3961025
Jain, Mohit
b068a610-75df-4624-b92f-6035714012ac
Garcia-Saura, Maria F.
a3df7c56-91cf-476d-8de8-ce31a42c13e4
Fernandez, Bernadette O.
27babc73-7646-4908-86e2-6c29d79fb938
Sawyer, Douglas B.
19e717d5-0a6f-4a01-aff5-fabc03016d89
Handy, Diane E.
65724761-f537-44fa-a42c-3999b47726dc
Loscalzo, Joseph
693bbc82-3c0e-4209-b7f6-5c8632fb4257
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Liao, Ronglih
a5f01676-e70d-41a6-95f8-4fcbd177cd16

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. American Journal of Physiology: Heart and Circulatory Physiology, 297 (6), H2144-H2153. (doi:10.1152/ajpheart.00673.2009). (PMID:19801492)

Record type: Article

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.

This record has no associated files available for download.

More information

e-pub ahead of print date: 2 October 2009
Published date: 1 December 2009
Keywords: ischemia, reperfusion, gender, free radicals, antioxidants, ascorbate, nitric oxide, nitrite
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 337702
URI: http://eprints.soton.ac.uk/id/eprint/337702
ISSN: 0363-6135
PURE UUID: 01f0650b-5cb5-49a8-9e69-54a75eb54c41
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

Catalogue record

Date deposited: 02 May 2012 13:09
Last modified: 15 Mar 2024 03:41

Export record

Altmetrics

Contributors

Author: Chee Chew Lim
Author: Nathan S. Bryan
Author: Mohit Jain
Author: Maria F. Garcia-Saura
Author: Bernadette O. Fernandez
Author: Douglas B. Sawyer
Author: Diane E. Handy
Author: Joseph Loscalzo
Author: Martin Feelisch ORCID iD
Author: Ronglih Liao

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×