Novel role of NADPH oxidase in ischemic myocardium: a study with Nox2 knockout mice.
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 β-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.
Molecular Cardiology and Angiogenesis Laboratory, Department of Surgery, University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT, USA.
Mahesh
M
Thirunavukkarasu
Ram Sudheer
RS
Adluri
Bela
B
Juhasz
Samson Mathews
SM
Samuel
Lijun
L
Zhan
Anupinder
A
Kaur
Gautam
G
Maulik
Juan A
JA
Sanchez
Janet
J
Hager
Nilanjana
N
Maulik
D000818:Animals; D017209:Apoptosis; D062186:Arterial Pressure; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D017202:Myocardial Ischemia / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D015425:Myocardial Reperfusion / Q000379:methods; D032383:Myocytes, Cardiac / Q000473:pathology; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D046888:Tissue Array Analysis; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
C495267:CTNNB1 protein, mouse; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D051176:beta Catenin; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases