The oxygen free radicals control MMP-9 and transcription factors expression in the spontaneously hypertensive rat.
Oxygen free radical and matrix metalloproteinases-9 (MMP-9) play an important pathophysiological role in the development of chronic hypertension. MMP-9 activities are regulated at different levels. We hypothesize that as mediators of the expression of MMP-9 the transcription factors like nuclear factor kappa B (NF-κB), c-fos and retinoic acid receptors-α (RAR-α) with binding sites to the MMP-9 promoter are overexpressed in the spontaneously hypertensive rat (SHR) in a process that is regulated by oxygen free radicals. Transcription factor NF-κB, c-fos and RAR-α expression levels were determined by immunohistochemistry in renal, cardiac and mesentery microcirculation of the SHR and its normotensive control, the Wistar Kyoto (WKY) rat. The animals were treated with a superoxide scavenger (Tempol) for eight weeks. The elevated plasma levels of thiobarbituric acid reactive substances and MMP-9 levels in the SHR were significantly decreased by Tempol treatment (P<0.05). The NF-κB, c-fos and RAR-α expression levels in renal glomerular, heart and mesentery microvessels were enhanced in the SHR and could also be reduced by Tempol compared to untreated animals (P<0.05). The enhanced MMP-9 levels in SHR microvessels co-express with transcription factors. These results suggest that elevated NF-κB, c-fos and RAR-α expressions and MMP-9 activity in the SHR are superoxide-dependent.
Department of Bioengineering, Institute of Engineering in Medicine, University of California, San Diego, La Jolla, CA 92093-0412, USA; Division of Physiology, Department of Preclinical Science, Faculty of Medicine, Thammasat University, Pathum Thani 12121, Thailand.
Naphatsanan
N
Duansak
Geert W
GW
Schmid-Schönbein
D000818:Animals; D001665:Binding Sites; D001794:Blood Pressure; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D006973:Hypertension / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D055806:Microvessels / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation
D016166:Free Radical Scavengers; D016328:NF-kappa B; D016760:Proto-Oncogene Proteins c-fos; C000607073:Rara protein, rat; D017382:Reactive Oxygen Species; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D017392:Thiobarbituric Acid Reactive Substances; D014157:Transcription Factors; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat