Thromboxane A2/prostaglandin H2-stimulated mitogenesis of coronary artery smooth muscle cells involves activation of mitogen-activated protein kinase and S6 kinase.

Morinelli, Thomas A.; Zhang, Liming; Newman, Walter H.; Meier, Kathryn E.

doi:10.1016/s0021-9258(17)37516-6

Cited by 104 publications

(8 citation statements)

References 37 publications

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“…When both inducers were used at concentrations that produced a similar induction of Cox-2, the ability of U46619 to elicit ERK2 phosphorylation and activation was very low compared with that of FGF-2. In addition, as reported by Morinelli et al [5], U46619 failed to induce a biphasic and sustained activation of ERK2 comparable with that of FGF-2. A recent study reports that PGF # α and 8-epi-PGF # α , presumably acting on TX receptors, induce a sustained increase in MAPK activity (up to 2 h) in porcine carotid artery SMCs [23].…”

Section: Discussionsupporting

confidence: 78%

“…TXA # and other eicosanoids have profound effects on SMC contractility. Various reports suggest a possible role for these mediators in cell growth, and recent publications have shown that TX mimetics such as U46619 activate the ERK pathway [6][7][8] and stimulate p85\S6 kinase [5]. However, recent studies [8,22] failed to show a significant effect of U46619 on cell growth in spite of an increased activity of ERK2 and other upstream signalling molecules such as Shc-GRB2 complexes [8].…”

Section: Discussionmentioning

confidence: 99%

“…Stimulation of ERK by a TX receptor agonist has been reported in cultured guinea-pig coronary SMCs [5]. We determined the time-dependent effect of U46619 (300 nM) and FGF-2 (0n1 ng\ml) on ERK2 activation at concentrations inducing [$H]thymidine incorporation.…”

Section: Time-dependent Effect Of U46619 and Fgf-2 On Mapk Activationmentioning

confidence: 99%

“…Thromboxane A # (TXA # ) is the main metabolite of arachidonic acid in platelets ; it is a mediator in the amplification loop of platelet aggregation and a potent vasoconstrictor of SMCs [4]. These cells possess TX receptors associated with vasoconstriction but recent results suggest that this mediator acts on extracellular signal-regulated kinases (ERKs) and p85\S6 protein kinase [5] ; it could thus have a role in proliferation [5][6][7]. Therefore the end effects of the G-proteincoupled seven-membrane-spanning TXA # receptor could be similar to those reported for growth factors with receptor tyrosine kinases.…”

Section: Introductionmentioning

confidence: 99%

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Regulatory role of prostaglandin E2 in induction of cyclo-oxygenase-2 by a thromboxane A2 analogue (U46619) and basic fibroblast growth factor in porcine aortic smooth-muscle cells

Karim

Berrou

Lévy-Toledano

et al. 1997

Biochemical Journal

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U46619, a thromboxane A2 analogue, and basic fibroblast growth factor (FGF-2) both induced the expression of the inducible cyclo-oxygenase (Cox)-2 in porcine aortic smooth-muscle cells. This induction was dose-dependent (submaximal at 300 nM for U46619 and 1 ng/ml for FGF-2) and time-dependent, with similar intensity and maximal expression at 2 h. Under these conditions, both inducers stimulated rapid activation of extracellular signal-regulated kinase (ERK2) at 5-10 min, a transient and lower intensity being induced by U46619 whereas that induced by FGF-2 was sustained (>1 h). PD98059, an inhibitor of the ERK pathway, inhibited the expression of Cox-2. In contrast, activation of Jun-N-terminal kinase (JNK1) was sustained with U46619 but poorly induced by FGF-2. Cox-2 expression induced by U46619 or FGF-2 was similarly reduced by prostaglandin (PGE2), forskolin or dibutyryl-cAMP, suggesting a regulatory effect of adenylate cyclase on Cox-2 expression. However, activation of ERK2 by FGF-2 was not affected by PGE2 whereas that of JNK1 by U46619 was inhibited, suggesting that inhibition of COX-2 expression by cAMP may be downstream of ERK2. The effects of PGE2 and forskolin on Cox-2 and phosphorylation of JNK1 were reversed with the protein kinase A inhibitor H89. In addition, endogenous PGE2 down-regulated the expression of Cox-2 by the two inducers, as stimulation of the cells in the presence of different Cox inhibitors increased the expression of the protein. Overall, these results suggest that exogenous and endogenous PGE2 exert negative inhibitory effects on Cox-2 expression mediated by stimulation of protein kinase A.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Time-dependent Effect Of U46619 and Fgf-2 On Mapk Activationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Regulatory role of prostaglandin E2 in induction of cyclo-oxygenase-2 by a thromboxane A2 analogue (U46619) and basic fibroblast growth factor in porcine aortic smooth-muscle cells

Karim

Berrou

Lévy-Toledano

et al. 1997

Biochemical Journal

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“…At present, it is thought that proliferation of the pulmonary arterioles is dominated by the proliferation of smooth muscle cells to create more muscular arterioles and increase resistance of distal arteries (4,(9)(10)(11), leading to PAH. Various vasoactive substances such as 5-HT, endothelin, and angiotensin, and growth factors, such as platelet-derived growth factor, epidermal growth factor, and transforming growth factor, can promote pulmonary arterial smooth muscle cell (PASMC) proliferation likely via the TRPC channel, which regulates intracellular calcium to cause vasoconstriction, increased vascular tone, and promote cell proliferation (6,(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Calcineurin/NFAT (nuclear factor of activated T cells) signalling pathway is involved in cell proliferation (21).…”

Section: Introductionmentioning

confidence: 99%

5-HT promotes pulmonary arterial smooth muscle cell proliferation through the TRPC channel

Junli

Tian

Liu

et al. 2018

Cell Mol Biol (Noisy-le-grand)

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Pulmonary arterial hypertension is caused by an imbalance of pulmonary vasoconstriction and vasodilation. Pulmonary arteriolar remodeling is a primary pathological change and proliferation of pulmonary arterial smooth muscle cells (PASMC) is an important pathological basis for pulmonary arteriolar remodeling. Vasoactive substances, such as 5-HT, may play a role in proliferation of PASMC via unknown mechanisms. In vitro experiments with PASMC showed that the TRPC channel inhibitor SKF96365 inhibited the effects 5-HT and DOI on PASMC proliferation and G2M percentage increase, and decreased expression of TRPC1, TRPC6 and calcineurin A/NFATc3 induced by 5-HT and DOI. SKF96365 inhibited binding of NFATc3 and DNA promoted by 5-HT and DOI. Therefore, 5-HT may affect the TRPC channel to promote proliferation of PASMC; upregulate expression of TRPC1, TRPC6, and calcineurin A/NFATc3; and therefore promote NFATc3 nuclear translocation. There may be crosstalk between 5-HT and TRPC, which may contribute to the pathogeneis of pulmonary arterial hypertension and this may be a novel therapeutic target for treating pulmonary arterial hypertension.

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17-B estradiol elicits an autocrine leiomyoma cell proliferation: Evidence for a stimulation of protein kinase-dependent pathway

Barbarisi¹,

Petillo

Lieto

et al. 2001

J. Cell. Physiol.

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The mechanism by which estradiol (E2) acts on cell proliferation is still unclear. In this paper, we report the results of a series of experiments in an attempt to elucidate the effector pathway(s) involved in coupling the E2 receptors binding to cellular growth response in leiomyoma cells (LSMC). Under conditions of E2-dependent growth, E2 treatment of LSMC triggers rapid and transient activation of the MAP-kinase pathway. Interestingly, we demonstrate that the early downstream signal transduction events determined by E2-stimulation in quiescent LSMC, including the rapid protein tyrosine phosphorylation of a subset of intracellular proteins, such GAP, PI-3-K, and PLCgamma, and the concomitant activation of ancillary protein kinases, are related to E2-induced PDGF secretion. Moreover, we identify the PDGF, alone or in association with other growth factors, as the main growth factor involved in the proliferation response of LSMC to E2 stimulation. The addition of neutralizing antibodies anti-PDGF was able to inhibit the mitogenic activity present in LSMC conditioned media samples. On the other hand, E2 did not affect the constitutive expression as well as the ligand affinity of PDGF receptors on LSMC plasmamembrane. Cell treatment with the antiestrogen ICI 182780 correlate both with a perturbation of E2-induced transductional circuit and with the disappearance of the mitogenic factor, PDGF, in LSMC conditioned media; the latter therefore, represents the main autocrine mediator of cell growth modulation, upregulated by E2 and down-regulated by antiestrogenic compound. Our experiments suggest that growth factor secretion is an initial and integral part of the signaling events mediated by the estradiol receptors, not related, at least in part, to E2 transcriptional modulation.

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Thromboxane A2/prostaglandin H2-stimulated mitogenesis of coronary artery smooth muscle cells involves activation of mitogen-activated protein kinase and S6 kinase.

Cited by 104 publications

References 37 publications

Regulatory role of prostaglandin E2 in induction of cyclo-oxygenase-2 by a thromboxane A2 analogue (U46619) and basic fibroblast growth factor in porcine aortic smooth-muscle cells

Regulatory role of prostaglandin E2 in induction of cyclo-oxygenase-2 by a thromboxane A2 analogue (U46619) and basic fibroblast growth factor in porcine aortic smooth-muscle cells

5-HT promotes pulmonary arterial smooth muscle cell proliferation through the TRPC channel

17-B estradiol elicits an autocrine leiomyoma cell proliferation: Evidence for a stimulation of protein kinase-dependent pathway

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