PMID: 8947476Nov 15, 1996Paper

Treatment of vascular smooth muscle cells with antisense phosphorothioate oligodeoxynucleotides directed against p42 and p44 mitogen-activated protein kinases abolishes DNA synthesis in response to platelet-derived growth factor

The Biochemical Journal
C J RobinsonR Plevin

Abstract

We have investigated the requirement for mitogen-activated protein (MAP) kinase in the stimulation of DNA synthesis by platelet-derived growth factor (PDGF) in rat aortic smooth muscle cells using a phosphorothioate-modified oligodeoxy-nucleotide (ODN) to deplete MAP kinase. Treatment for 72 h with MAP kinase antisense ODN directed against both the p42 and p44 isoforms of MAP kinase abolished the expression of MAP kinase and reduced agonist-stimulated MAP kinase activity by approx. 95%. The scrambled control ODN was without effect, but the sense control ODN slightly enhanced the expression of both isoforms. Abolition of MAP kinase activity by antisense ODN treatment prevented angiotensin II- and PDGF-stimulated activation of p90 ribosomal S6 kinase activity, but did not affect activation of MAP kinase kinase. In addition, antisense ODN pretreatment reduced PDGF-stimulated [3H]thymidine incorporation to < 5% of control, and decreased basal incorporation by approx. 90%. In contrast, basal [3H]thymidine incorporation was enhanced approx. 60% by control sense ODN treatment. These results indicate an obligatory role for MAP kinase in the activation of a number of early events in mitogenesis, including DNA synthesis, in vascular smoo...Continue Reading

Citations

Sep 8, 1998·The American Journal of Physiology·S S El-DahrW H Baricos
Apr 6, 2001·American Journal of Physiology. Lung Cellular and Molecular Physiology·J H LeeJ L Black
Apr 24, 2003·The Journal of Biological Chemistry·Christopher CalabreseRichard Gilbertson
Dec 9, 2004·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Sabine C WolfBernhard R Brehm
Jul 2, 1999·International Journal of Cancer. Journal International Du Cancer·K B ReddyC A Diglio
Jan 15, 1999·Arteriosclerosis, Thrombosis, and Vascular Biology·X P XiR E Law
May 18, 1999·The American Journal of Physiology·H Y LinP J Davis
Nov 5, 1999·Journal of Biomedical Science·S P WuP W Gean
Mar 21, 1998·Cellular Signalling·M G Thompson, R M Palmer

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