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Nrf2 Deficiency Exaggerates Doxorubicin-Induced Cardiotoxicity and Cardiac Dysfunction
Joint Authors
Janicki, Joseph S.
Li, Siying
Wang, Wenjuan
Niu, Ting
Wang, Hui
Li, Bin
Shao, Lei
Lai, Yimu
Li, Huanjie
Wang, Xing Li
Tang, Dongqi
Cui, Taixing
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-15, 15 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-05-06
Country of Publication
Egypt
No. of Pages
15
Main Subjects
Abstract EN
The anticancer therapy of doxorubicin (Dox) has been limited by its acute and chronic cardiotoxicity.
In addition to a causative role of oxidative stress, autophagy appears to play an important role in the regulation of Dox-induced cardiotoxicity.
However, the underlying mechanisms remain unclear.
Accordingly, we explored a role of nuclear factor erythroid-2 related factor 2 (Nrf2) in Dox-induced cardiomyopathy with a focus on myocardial oxidative stress and autophagic activity.
In wild type (WT) mice, a single intraperitoneal injection of 25 mg/kg Dox rapidly induced cardiomyocyte necrosis and cardiac dysfunction, which were associated with oxidative stress, impaired autophagy, and accumulated polyubiquitinated protein aggregates.
However, these Dox-induced adverse effects were exaggerated in Nrf2 knockout (Nrf2−/−) mice.
In cultured cardiomyocytes, overexpression of Nrf2 increased the steady levels of LC3-II, ameliorated Dox-induced impairment of autophagic flux and accumulation of ubiquitinated protein aggregates, and suppressed Dox-induced cytotoxicity, whereas knockdown of Nrf2 exerted opposite effects.
Moreover, the exaggerated adverse effects in Dox-intoxicated Nrf2 depleted cardiomyocytes were dramatically attenuated by forced activation of autophagy via overexpression of autophagy related gene 5 (Atg5).
Thus, these results suggest that Nrf2 is likely an endogenous suppressor of Dox-induced cardiotoxicity by controlling both oxidative stress and autophagy in the heart.
American Psychological Association (APA)
Li, Siying& Wang, Wenjuan& Niu, Ting& Wang, Hui& Li, Bin& Shao, Lei…[et al.]. 2014. Nrf2 Deficiency Exaggerates Doxorubicin-Induced Cardiotoxicity and Cardiac Dysfunction. Oxidative Medicine and Cellular Longevity،Vol. 2014, no. 2014, pp.1-15.
https://search.emarefa.net/detail/BIM-1047108
Modern Language Association (MLA)
Li, Siying…[et al.]. Nrf2 Deficiency Exaggerates Doxorubicin-Induced Cardiotoxicity and Cardiac Dysfunction. Oxidative Medicine and Cellular Longevity No. 2014 (Dec. 2014), pp.1-15.
https://search.emarefa.net/detail/BIM-1047108
American Medical Association (AMA)
Li, Siying& Wang, Wenjuan& Niu, Ting& Wang, Hui& Li, Bin& Shao, Lei…[et al.]. Nrf2 Deficiency Exaggerates Doxorubicin-Induced Cardiotoxicity and Cardiac Dysfunction. Oxidative Medicine and Cellular Longevity. 2014. Vol. 2014, no. 2014, pp.1-15.
https://search.emarefa.net/detail/BIM-1047108
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1047108