Genetic redox preconditioning differentially modulates AP-1 and NFκB responses following cardiac ischemia/reperfusion injury and protects against necrosis and apoptosis

Jusan Yang; Jennifer J Marden; Chenguang Fan; Salih Sanlioglu; Robert M Weiss; Teresa C Ritchie; Robin L Davisson; John F Engelhardt

doi:10.1016/S1525-0016(02)00061-8

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Genetic redox preconditioning differentially modulates AP-1 and NFκB responses following cardiac ischemia/reperfusion injury and protects against necrosis and apoptosis

Journal article

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Genetic redox preconditioning differentially modulates AP-1 and NFκB responses following cardiac ischemia/reperfusion injury and protects against necrosis and apoptosis

Jusan Yang, Jennifer J Marden, Chenguang Fan, Salih Sanlioglu, Robert M Weiss, Teresa C Ritchie, Robin L Davisson and John F Engelhardt

Molecular therapy, Vol.7(3), pp.341-353

03/2003

DOI: 10.1016/S1525-0016(02)00061-8

PMID: 12668130

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Abstract

Reactive oxygen species have been established as key mediators of cardiac injury following ischemia/reperfusion (I/R). We hypothesized that superoxide formation at different subcellular locations following cardiac I/R injury may differentially regulate cellular responses that determine pathophysiologic outcomes. Recombinant adenoviruses expressing Cu/ZnSOD or MnSOD were utilized to modulate superoxide levels in the cytoplasmic or mitochondrial compartments, respectively, prior to coronary artery I/R injury in the rat heart. Ectopic expression of both MnSOD and Cu/ZnSOD afforded protection from I/R injury, as evidenced by a significant reduction in serum creatine kinase levels, infarct size, malondialdehyde levels, and apoptotic cell death in comparison to controls. MnSOD and Cu/ZnSOD expression also significantly altered the kinetics of NFκB and AP-1 activation following I/R injury, characterized by a delayed induction of NFκB and abrogated AP-1 response. Western blot analysis of Bcl-2, Bcl-xL, Bad, Caspase 3, PDK1, and phospho-Akt also revealed SOD-mediated changes in gene expression consistent with protection and decreased apoptosis. These findings support the notion that both mitochondrial and cytoplasmic-derived SOD induce changes in AP-1 and NFκB activity, creating an antiapoptotic microenvironment within cardiomyocytes that affords protection following I/R injury.

Apoptosis

Gene Therapy

Heart

Ischemia

infarction

reperfusion

Details

Title: Subtitle: Genetic redox preconditioning differentially modulates AP-1 and NFκB responses following cardiac ischemia/reperfusion injury and protects against necrosis and apoptosis
Creators: Jusan Yang - Department of Anatomy & Cell Biology, Iowa City, Iowa 52242, USA
Jennifer J Marden - The Center for Gene Therapy of Cystic Fibrosis and Other Genetic Diseases, Iowa City, Iowa 52242, USA
Chenguang Fan - The Center for Gene Therapy of Cystic Fibrosis and Other Genetic Diseases, Iowa City, Iowa 52242, USA
Salih Sanlioglu - Department of Internal Medicine, Iowa City, Iowa 52242, USA
Robert M Weiss - Department of Internal Medicine, Iowa City, Iowa 52242, USA
Teresa C Ritchie - Department of Anatomy & Cell Biology, Iowa City, Iowa 52242, USA
Robin L Davisson - Department of Anatomy & Cell Biology, Iowa City, Iowa 52242, USA
John F Engelhardt - Department of Anatomy & Cell Biology, Iowa City, Iowa 52242, USA
Resource Type: Journal article
Publication Details: Molecular therapy, Vol.7(3), pp.341-353
DOI: 10.1016/S1525-0016(02)00061-8
PMID: 12668130
NLM abbreviation: Mol Ther
ISSN: 1525-0016
eISSN: 1525-0024
Publisher: Elsevier Inc
Language: English
Date published: 03/2003
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Cardiovascular Medicine; Radiation Oncology; Internal Medicine
Record Identifier: 9984025321302771

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