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

Mahesh Thirunavukkarasu, Ram Sudheer Adluri, Bela Juhasz, Samson Mathews Samuel, Lijun Zhan, Anupinder Kaur, Gautam Maulik, Juan A. Sanchez, Janet Hager, Nilanjana Maulik

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12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)501-514
Number of pages14
JournalFunctional and Integrative Genomics
Volume12
Issue number3
DOIs
Publication statusPublished - 1 Aug 2012
Externally publishedYes

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Keywords

  • Cardioprotection
  • Gene expression
  • Ischemic preconditioning
  • NADPH oxidase
  • Nox2

ASJC Scopus subject areas

  • Genetics

Cite this

Thirunavukkarasu, M., Adluri, R. S., Juhasz, B., Mathews Samuel, S., Zhan, L., Kaur, A., Maulik, G., Sanchez, J. A., Hager, J., & Maulik, N. (2012). Novel role of NADPH oxidase in ischemic myocardium: A study with Nox2 knockout mice. Functional and Integrative Genomics, 12(3), 501-514. https://doi.org/10.1007/s10142-011-0256-x