HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 291/6/H2636    most recent 00399.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by Nagy, N. Articles by Das, D. K. Search for Related Content PubMed PubMed Citation Articles by Nagy, N. Articles by Das, D. K.

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

Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, Connecticut; and Institute for Environmental Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania

Submitted 18 April 2006 ; accepted in final form 18 May 2006

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 H₂O₂-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 H₂O₂ 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.

redox signaling; reactive oxygen species; glutathione; catalase; glutathione peroxidase; peroxiredoxin gene knockout mice

This article has been cited by other articles:

				E. Schroder, J. P. Brennan, and P. Eaton Cardiac peroxiredoxins undergo complex modifications during cardiac oxidant stress Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H425 - H433. [Abstract] [Full Text] [PDF]

				E. Kubo, N. Fatma, Y. Akagi, D. R. Beier, S. P. Singh, and D. P. Singh TAT-mediated PRDX6 protein transduction protects against eye lens epithelial cell death and delays lens opacity Am J Physiol Cell Physiol, March 1, 2008; 294(3): C842 - C855. [Abstract] [Full Text] [PDF]

				A. Kumin, M. Schafer, N. Epp, P. Bugnon, C. Born-Berclaz, A. Oxenius, A. Klippel, W. Bloch, and S. Werner Peroxiredoxin 6 is required for blood vessel integrity in wounded skin J. Cell Biol., November 19, 2007; 179(4): 747 - 760. [Abstract] [Full Text] [PDF]

				S. Chatterjee, S. Baeter, and J. Bhattacharya Endothelial and epithelial signaling in the lung Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L517 - L519. [Abstract] [Full Text] [PDF]

				A. Tosaki and I. Edes The role of peroxiredoxins in ischemia-reperfusion-induced cardiac damage Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2586 - H2587. [Full Text] [PDF]