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Oxidative Medicine and Cellular Longevity
Volume 2016, Article ID 5638943, 14 pages
http://dx.doi.org/10.1155/2016/5638943
Research Article

Notch1 Pathway Protects against Burn-Induced Myocardial Injury by Repressing Reactive Oxygen Species Production through JAK2/STAT3 Signaling

1Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi 710032, China
2Department of Physiology, School of Basic Medical Sciences, Fourth Military Medical University, Xi’an, Shaanxi 710032, China
3First Student Brigade, Fourth Military Medical University, Xi’an, Shaanxi 710032, China

Received 28 September 2015; Accepted 9 November 2015

Academic Editor: Rajesh Mohanraj

Copyright © 2016 Weixia Cai et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Oxidative stress plays an important role in burn-induced myocardial injury, but the cellular mechanisms that control reactive oxygen species (ROS) production and scavenging are not fully understood. This study demonstrated that blockade of Notch signaling via knockout of the transcription factor RBP-J or a pharmacological inhibitor aggravated postburn myocardial injury, which manifested as deteriorated serum CK, CK-MB, and LDH levels and increased apoptosis in vitro and in vivo. Interruption of Notch signaling increased intracellular ROS production, and a ROS scavenger reversed the exacerbated myocardial injury after Notch signaling blockade. These results suggest that Notch signaling deficiency aggravated postburn myocardial injury through increased ROS levels. Notch signaling blockade also decreased MnSOD expression in vitro and in vivo. Notably, Notch signaling blockade downregulated p-JAK2 and p-STAT3 expression. Inhibition of JAK2/STAT3 signaling with AG490 markedly decreased MnSOD expression, increased ROS production, and aggravated myocardial injury. AG490 plus GSI exerted no additional effects. These results demonstrate that Notch signaling protects against burn-induced myocardial injury through JAK2/STAT3 signaling, which activates the expression of MnSOD and leads to decreased ROS levels.