Calcium- and superoxide anion-mediated mitogenic action of substance P on cardiac fibroblasts

dc.contributorKumaran, C
dc.contributorShivakumar, K
dc.date.accessioned2012-12-04T11:43:31Z
dc.date.available2012-12-04T11:43:31Z
dc.date.issued2002
dc.description.abstractSubstance P is released from nerve endings in the heart under pathological conditions like ischemia, but its action on cardiac cells has not been investigated. This study tested the hypothesis that substance P is mitogenic to adult cardiac fibroblasts and delineated the underlying mechanism(s). Substance P, acting via neurokinin-1 (NK-1) receptors, stimulated cellular hyperplasia over a range of 1-10 mumol/l. It elicited no change in net collagen production, total protein synthesis, or cell protein content but increased Ca-45 uptake and superoxide generation. EGTA, N-acetyl-cysteine, and superoxide dismutase attenuated the hyperplastic response to substance P. A combination of substance P and EGTA enhanced superoxide generation without an increase in DNA synthesis, showing that an increase in superoxide production does not result in hyperplasia when extracellular Ca2+ is chelated. Together, the data suggest that substance P may activate, via NK-1 receptors, a hyperplastic but not hypertrophic response in adult cardiac fibroblasts and that alterations in redox state and Ca2+ homeostasis may act in concert to mediate its mitogenic action.
dc.identifier.citationAMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY. 282; 5; H1855-H1862en_US
dc.identifier.urihttp://dx.doi.org/10.1152/ajpheart.00747.2001
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/pubmed/11959652
dc.identifier.urihttps://dspace.sctimst.ac.in/handle/123456789/190
dc.publisherAMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
dc.subjectBiochemistry
dc.titleCalcium- and superoxide anion-mediated mitogenic action of substance P on cardiac fibroblasts
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