Targeted disruption of peroxiredoxin 6 gene renders the heart vulnerable to ischemia-reperfusion injury

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Abstract

Peroxiredoxin 6 (Prdx6) is a novel peroxidase enzyme belonging to the Prdx family, which in mammals contains five more peroxiredoxins (Prdx1-Prdx5). Like glutathione peroxidase (GSHPx) and catalase, Prdx6 possesses H(2)O(2)-scavenging activities, and, like the former, it also removes hydroperoxides. Since significant amounts of catalase and GSHPx are present in the heart contributing toward the attenuation of H(2)O(2) and hydroperoxides formed during ischemia-reperfusion injury and thereby providing cardioprotection, we asked whether Prdx6 also has any role in this process. In the present study we used Prdx6(-/-) mice to assess the role of Prdx6 in ischemic injury. Western blot analysis revealed the absence of any Prdx activity in the Prdx6(-/-) mouse heart, while the GSHPx-1 and catalase levels remained unchanged. Randomly selected hearts from Prdx6(-/-) mice and wild-type mice were subjected to 30 min of global ischemia followed by 120 min of reperfusion at normothermia. The hearts from the Prdx6(-/-) mice were more susceptible to ischemic reperfusion injury as evidenced by reduced recovery of left ventricular function, increased myocardial infarct size, and higher amount of apoptotic cardiomyocytes compared with wild-type mouse hearts. These Prdx6(-/-) hearts were also subjected to a higher amount of oxidative stress as evidenced by the presence of higher amount of malondialdehyde. The present study thus indicates a nonredundant role of Prdx6 in myocardial ischemic reperfusion injury as catalase, and GSHPx could not make up for the deficiency of Prdx6 activities.

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