Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P51812 (mitogen-activated protein)
 10,636 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inhibitors of the production of endogenous angiotensin II (A-II) can diminish the hyperplastic response produced by arterial injury in animals; however, a similar effect in humans has not been observed. To explain this discrepancy, we compared the effect of A-II on rat aortic smooth muscle cells (R-SMC) and smooth muscle cells derived from human saphenous veins (H-SMC). A-II (10-1000 nM) significantly increased the proliferative rate of R-SMC incubated in 10% serum, but a similar effect was not observed with H-SMC. Incubation of R-SMC for 24 hr with A-II (1 microM) produced a significant increase in cell size (7%) and protein production (18%), whereas no hypertrophic response was noted in H-SMC exposed to A-II. In neither R-SMC nor H-SMC did A-II, in any concentration, induce cell migration. Stimulation of R-SMC with A-II resulted in tyrosine phosphorylation of five proteins (approximately 120, approximately 108, approximately 68, 45, 42 kDa). The 42- and 45-kDa proteins, which we have previously identified as mitogen-activated protein kinases (MAP-K), remained phosphorylated for 1 hr. In H-SMC, only MAP kinases were tyrosine phosphorylated, but with less intensity than in R-SMC, and only for 20 min. In protein kinase C-depleted SMC, tyrosine phosphorylation of MAP kinase was inhibited in both cell types. A-II produced hypertrophy and hyperplasia of R-SMC, but not H-SMC. Differences in intracellular signaling might account for these disparate effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of angiotensin II on human vascular smooth muscle cell growth. 804 Nov 34

We investigated the effects of PDGF on DNA synthesis and mitogen-activated protein (MAP) kinase activity, and demonstrated that the adult intimal SMC was concentration-dependently stimulated by all PDGF isoforms in terms of both [3H]thymidine incorporation and MAP kinase activation, with PDGF-BB and -AB being more potent than PDGF-AA. The intimal SMCs and the neonatal SMCs showed a similar response with regard to MAP kinase activation. On the other hand, the intimal SMCs expressed many more PDGF receptors than the adult medial SMCs, which expressed a greater amount of PDGF-A chain mRNA and showed a lesser response to PDGFs. These results suggest that the intimal SMCs have a relatively high potential to react to exogenous PDGFs, whereas the adult medial SMCs depend on endogenous or autocrine secretion of PDGF-AA.
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PMID:Response to platelet-derived growth factor by phenotypically different cultured human aortic smooth muscle cells. 958 95

Our goal in this review is to provide a comprehensive, integrated view of the numerous signaling pathways that are activated by alpha(1)-adrenoceptors and control actin-myosin interactions (i.e., crossbridge cycling and force generation) in mammalian arterial smooth muscle. These signaling pathways may be categorized broadly as leading either to thick (myosin) filament regulation or to thin (actin) filament regulation. Thick filament regulation encompasses both "Ca(2+) activation" and "Ca(2+)-sensitization" as it involves both activation of myosin light chain kinase (MLCK) by Ca(2+)-calmodulin and regulation of myosin light chain phosphatase (MLCP) activity. With respect to Ca(2+) activation, adrenergically induced Ca(2+) transients in individual smooth muscle cells of intact arteries are now being shown by high resolution imaging to be sarcoplasmic reticulum-dependent asynchronous propagating Ca(2+) waves. These waves differ from the spatially uniform increases in [Ca(2+)] previously assumed. Similarly, imaging during adrenergic activation has revealed the dynamic translocation, to membranes and other subcellular sites, of protein kinases (e.g., Ca(2+)-activated protein kinases, PKCs) that are involved in regulation of MLCP and thus in "Ca(2+) sensitization" of contraction. Thin filament regulation includes the possible disinhibition of actin-myosin interactions by phosphorylation of CaD, possibly by mitogen-activated protein (MAP) kinases that are also translocated during adrenergic activation. An hypothesis for the mechanisms of adrenergic activation of small arteries is advanced. This involves asynchronous Ca(2+) waves in individual SMC, synchronous Ca(2+) oscillations (at high levels of adrenergic activation), Ca(2+) sparks, "Ca(2+)-sensitization" by PKC and Rho-associated kinase (ROK), and thin filament mechanisms.
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PMID:Alpha1-adrenergic signaling mechanisms in contraction of resistance arteries. 1288 52

Chlorotyrosine is an oxidative product of hypochlorous acid and l-tyrosine, and is considered as a biomarker for oxidative stress and cardiovascular disease. However, it is not clear whether chlorotyrosine could directly contribute to vascular pathogenesis. In this study, we investigated the effect and potential mechanisms of chlorotyrosine on human aortic smooth muscle cell (AoSMC) migration. With Boyden chamber and wound healing assays, chlorotyrosine significantly increased AoSMC migration in a concentration- and time-dependent manner. In addition, chlorotyrosine significantly increased the expression of several key molecules related to cell migration including PDGF receptor-B (PDGFR-B), matrix metalloproteinases (MMP-1 and MMP-2) and integrins (alpha3, alphaV, and beta3) in AoSMC at both mRNA and protein levels. Furthermore, chlorotyrosine also increased superoxide anion generation in AoSMC with the fluorescent dye dihydroethidium (DHE) staining. Activation of mitogen-activated protein kinases (MAPKs) was analyzed with Bio-Plex Luminex immunoassay and Western blotting. Chlorotyrosine induced a transient phosphorylation of ERK1/2, but not JNK and p38 MAPKs. Antioxidants including selenomethionine (SeMet) and Mn(III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) as well as ERK1/2 inhibitor PD98059 effectively blocked chlorotyrosine-induced AoSMC migration. Thus, these findings demonstrate new biological functions of chlorotyrosine in human SMC migration, which may play a crucial role in the vascular lesion formation.
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PMID:Chlorotyrosine promotes human aortic smooth muscle cell migration through increasing superoxide anion production and ERK1/2 activation. 1828 Oct 51