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Nrf2 Deficiency Unmasks the Significance of Nitric Oxide Synthase Activity for Cardioprotection
Joint Authors
Erkens, Ralf
Suvorava, Tatsiana
Sutton, Thomas R.
Fernandez, Bernadette O.
Mikus-Lelinska, Monika
Barbarino, Frederik
Flögel, Ulrich
Feelisch, Martin
Cortese-Krott, Miriam M.
Kelm, Malte
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-15, 15 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-04-30
Country of Publication
Egypt
No. of Pages
15
Main Subjects
Abstract EN
The transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a key master switch that controls the expression of antioxidant and cytoprotective enzymes, including enzymes catalyzing glutathione de novo synthesis.
In this study, we aimed to analyze whether Nrf2 deficiency influences antioxidative capacity, redox state, NO metabolites, and outcome of myocardial ischemia reperfusion (I/R) injury.
In Nrf2 knockout (Nrf2 KO) mice, we found elevated eNOS expression and preserved NO metabolite concentrations in the aorta and heart as compared to wild types (WT).
Unexpectedly, Nrf2 KO mice have a smaller infarct size following myocardial ischemia/reperfusion injury than WT mice and show fully preserved left ventricular systolic function.
Inhibition of NO synthesis at onset of ischemia and during early reperfusion increased myocardial damage and systolic dysfunction in Nrf2 KO mice, but not in WT mice.
Consistent with this, infarct size and diastolic function were unaffected in eNOS knockout (eNOS KO) mice after ischemia/reperfusion.
Taken together, these data suggest that eNOS upregulation under conditions of decreased antioxidant capacity might play an important role in cardioprotection against I/R.
Due to the redundancy in cytoprotective mechanisms, this fundamental antioxidant property of eNOS is not evident upon acute NOS inhibition in WT mice or in eNOS KO mice until Nrf2-related signaling is abrogated.
American Psychological Association (APA)
Erkens, Ralf& Suvorava, Tatsiana& Sutton, Thomas R.& Fernandez, Bernadette O.& Mikus-Lelinska, Monika& Barbarino, Frederik…[et al.]. 2018. Nrf2 Deficiency Unmasks the Significance of Nitric Oxide Synthase Activity for Cardioprotection. Oxidative Medicine and Cellular Longevity،Vol. 2018, no. 2018, pp.1-15.
https://search.emarefa.net/detail/BIM-1212198
Modern Language Association (MLA)
Erkens, Ralf…[et al.]. Nrf2 Deficiency Unmasks the Significance of Nitric Oxide Synthase Activity for Cardioprotection. Oxidative Medicine and Cellular Longevity No. 2018 (2018), pp.1-15.
https://search.emarefa.net/detail/BIM-1212198
American Medical Association (AMA)
Erkens, Ralf& Suvorava, Tatsiana& Sutton, Thomas R.& Fernandez, Bernadette O.& Mikus-Lelinska, Monika& Barbarino, Frederik…[et al.]. Nrf2 Deficiency Unmasks the Significance of Nitric Oxide Synthase Activity for Cardioprotection. Oxidative Medicine and Cellular Longevity. 2018. Vol. 2018, no. 2018, pp.1-15.
https://search.emarefa.net/detail/BIM-1212198
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1212198