Novel role of NADPH oxidase in ischemic myocardium: a study with Nox2 knockout mice

被引:19
作者
Thirunavukkarasu, Mahesh [1 ]
Adluri, Ram Sudheer [1 ]
Juhasz, Bela [2 ]
Samuel, Samson Mathews [1 ]
Zhan, Lijun [1 ]
Kaur, Anupinder [3 ]
Maulik, Gautam [4 ]
Sanchez, Juan A. [5 ]
Hager, Janet [3 ]
Maulik, Nilanjana [1 ]
机构
[1] Univ Connecticut, Sch Med, Mol Cardiol & Angiogenesis Lab, Dept Surg, Farmington, CT 06032 USA
[2] Univ Debrecen, Dept Pharmacol, H-4012 Debrecen, Hungary
[3] Univ Connecticut, Sch Med, Dept Genet & Dev Biol, Translat Genom Core, Farmington, CT 06032 USA
[4] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA
[5] St Marys Hosp, Dept Surg, Waterbury, CT USA
关键词
Ischemic preconditioning; Nox2(-/-); NADPH oxidase; Gene expression; Cardioprotection; BETA-CATENIN; PROMOTES ANGIOGENESIS; CARDIOPROTECTION; ACTIVATION; STRESS; OXYGEN; RAT; HYPERTROPHY; MECHANISMS; EXPRESSION;
D O I
10.1007/s10142-011-0256-x
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Several potential sources of reactive oxygen species (ROS) in cells exist. One source is NADPH oxidase, which is especially important for superoxide radical production. Nox2 is a primary regulatory subunit of NADPH oxidase. In the present study, we examined the role of ROS and NADPH oxidase in ischemic preconditioning (IP)-mediated cardioprotection by using Nox2(-/-) mice. Both wild-type (WT) and Nox2(-/-) mice were subjected to either 30 min of ischemia followed by 2 h of reperfusion (IR) or IP prior to 30 min ischemia and 2 h of reperfusion. Reduction in left ventricular developed pressure (60.1 versus 63 mmHg), dp/dt (max) (893 versus 1,027 mmHg/s), and aortic flow (0.9 versus 1.8 ml/min) was observed in Nox2(-/-)IPIR compared to WTIPIR along with increased infarct size (33% versus 22%) and apoptosis after 120 min of reperfusion. Differentially regulated genes were demonstrated by comparing gene expression in WTIPIR versus Nox2(-/-) IPIR hearts. Selected differentially regulated genes such as beta-catenin, SRPK3, ERDR1, ACIN1, Syntaxin-8, and STC1 were validated by real-time PCR. Taken together, this is the first report identifying important, differentially expressed genes during ischemic preconditioning in Nox2(-/-) mice by using microarray analysis.
引用
收藏
页码:501 / 514
页数:14
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