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dc.contributor.authorOliveira, LCB de
dc.contributor.authorOliveira, CJR [UNIFESP]
dc.contributor.authorFries, D. M.
dc.contributor.authorStern, A.
dc.contributor.authorMonteiro, Hugo Pequeno [UNIFESP]
dc.identifier.citationBrazilian Journal Of Medical And Biological Research. Sao Paulo: Assoc Bras Divulg Cientifica, v. 35, n. 2, p. 181-190, 2002.
dc.description.abstractPrevious studies have shown that exogenously generated nitric oxide (NO) inhibits smooth muscle cell proliferation. In the present study, we stimulated rabbit vascular smooth muscle cells (RVSMC) with E. coli lipopolysaccharide (LPS), a known inducer of NO synthase transcription, and established a connection between endogenous NO, phosphorylation/dephosphorylation-mediated signaling pathways, and DNA synthesis. Non-confluent RVSMC were cultured with 0, 5, 10, or 100 ng/ml of the endotoxin. NO release was increased by 86.6% (maximum effect) in low-density cell cultures stimulated with 10 ng/ml LPS as compared to non-stimulated controls. Conversely, LPS (5 to 100 ng/ml) did not lead to enhanced NO production in multilayered (high density) RVSMC. DNA synthesis measured by thymidine incorporation showed that LPS was mitogenic only to non-confluent RVSMC; furthermore, the effect was prevented statistically by aminoguanidine (AG), a potent inhibitor of the inducible NO synthase, and oxyhemoglobin, an NO scavenger. Finally, there was a cell density-dependent LPS effect on protein tyrosine phosphatase (PTP) and ERK1/ERK2 mitogen-activated protein (MAP) kinase activities. Shortterm transient stimulation of ERK1/ERK2 MAP kinases was maximal at 12 min in non-confluent RVSMC and was prevented by preincubation with AG, whereas PTP activities were inhibited in these cells after 24-h LPS stimulation. Conversely, no significant LPS-mediated changes in kinase or phosphatase activities were observed in high-density cells. LPS-induced NO generation by RVSMC may switch on a cell density-dependent proliferative signaling cascade, which involves the participation of PTP and the ERK1/ERK2 MAP kinases.en
dc.publisherAssoc Bras Divulg Cientifica
dc.relation.ispartofBrazilian Journal Of Medical And Biological Research
dc.rightsAcesso aberto
dc.subjectnitric oxideen
dc.subjectprotein tyrosine phosphatasesen
dc.subjectmitogen-activated protein kinasesen
dc.subjectDNA synthesisen
dc.subjectcell densityen
dc.titleEffects of lipopolysaccharide on low- and high-density cultured rabbit vascular smooth muscle cells: differential modulation of nitric oxide release, ERK1/ERK2 MAP kinase activity, protein tyrosine phosphatase activity, and DNA synthesisen
dc.contributor.institutionFundacao Prosangue Hemoctr Sao Paulo
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionNYU Med Ctr
dc.description.affiliationFundacao Prosangue Hemoctr Sao Paulo, Dept Bioquim, BR-05403000 Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Escola Paulista Med, Disciplina Biol Mol, Sao Paulo, Brazil
dc.description.affiliationNYU Med Ctr, Dept Pharmacol, New York, NY 10016 USA
dc.description.affiliationUnifespUniv Fed Sao Paulo, Escola Paulista Med, Disciplina Biol Mol, Sao Paulo, Brazil
dc.description.sourceWeb of Science

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