TY - JOUR
T1 - Novel role of NADPH oxidase in ischemic myocardium
T2 - A study with Nox2 knockout mice
AU - Thirunavukkarasu, Mahesh
AU - Adluri, Ram Sudheer
AU - Juhasz, Bela
AU - Samuel, Samson Mathews
AU - Zhan, Lijun
AU - Kaur, Anupinder
AU - Maulik, Gautam
AU - Sanchez, Juan A.
AU - Hager, Janet
AU - Maulik, Nilanjana
N1 - Funding Information:
All animals received care in compliance with the principles of laboratory animal care formulated by the National Society for Medical Research and Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health. The Nox2−/− (strain name: B6.129S- Cybbtm1Din/J) (stock # 002365) mice were purchased from Jackson Laboratory (Bar Harbor, ME, USA).
Funding Information:
Acknowledgments This study was supported by the National Institute of Health (USA) grants HL-56803, HL-69910, and HL-85804 to NM.
PY - 2012/8
Y1 - 2012/8
N2 - Abstract 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/dtmax (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.
AB - Abstract 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/dtmax (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.
KW - Cardioprotection
KW - Gene expression
KW - Ischemic preconditioning
KW - NADPH oxidase
KW - Nox2
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U2 - 10.1007/s10142-011-0256-x
DO - 10.1007/s10142-011-0256-x
M3 - Article
C2 - 22038056
AN - SCOPUS:84870299120
SN - 1438-793X
VL - 12
SP - 501
EP - 514
JO - Functional and Integrative Genomics
JF - Functional and Integrative Genomics
IS - 3
ER -