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Hypoxia and antioxidants enhance soluble ICAM-1 release from cardiac fibroblasts.

Sapna, S; Shivakumar, K; (2007) Hypoxia and antioxidants enhance soluble ICAM-1 release from cardiac fibroblasts. Mol Cell Biochem , 303 (1-2) pp. 259-262. 10.1007/s11010-007-9475-9.

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Abstract

Intercellular adhesion molecule-1 plays a key role in mediating inflammatory and immune responses. There is also increasing appreciation of the role of its soluble form, sICAM-1, in regulating inflammation. This study evaluated the effects of hypoxia and N-acetyl-L-cysteine on sICAM-1 production by adult rat cardiac fibroblasts. By ELISA, hypoxia was found to cause a 61% increase in sICAM-1 in cardiac fibroblast culture supernates. However, RT-PCR did not reveal a concomitant increase in cell surface ICAM-1 transcript levels, suggesting that the increase in sICAM-1 may involve post-transcriptional and/or post-translational mechanisms. Using pharmacological inhibitors, it was observed that p42/44 MAPK and PKC mediate the stimulatory effect of hypoxia on sICAM-1 production. Remarkably, N-acetyl-L-cysteine caused a 3-fold increase in sICAM-1 by p42/44 MAPK-, p38 MAPK- and PKC-independent mechanisms. Pyrrolidine dithiocarbamate, another potent antioxidant, also augmented sICAM-1. The findings presented in this communication underscore the link between redox status and sICAM-1 release from cardiac fibroblasts. Further, because hypoxia is a major component of myocardial ischemia and is pro-inflammatory, and both N-acetylcysteine and pyrrolidine dithiocarbamate are clinically used antioxidants, the observations may have clinical significance.

Type: Article
Title: Hypoxia and antioxidants enhance soluble ICAM-1 release from cardiac fibroblasts.
Location: Netherlands
DOI: 10.1007/s11010-007-9475-9
Keywords: Acetylcysteine, Animals, Cell Hypoxia, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Fibroblasts, Free Radical Scavengers, Heart Ventricles, Intercellular Adhesion Molecule-1, Male, Mitogen-Activated Protein Kinases, Protein Kinase C, Rats, Rats, Sprague-Dawley, Reverse Transcriptase Polymerase Chain Reaction
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science
URI: http://discovery.ucl.ac.uk/id/eprint/1552507
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