Heparin inhibits mitogen-activated protein kinase activation in intact rat vascular smooth muscle cells

Heparin is potently antiproliferative for vascular smooth muscle cells in vivo and in vitro, inhibiting early proto-oncogene expression and blocking proliferation in the G1 phase of the cell cycle. The mitogen-activated protein kinase (MAPK) family of serine- and threonine-specific kinases is activa...

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Published inThe Journal of biological chemistry Vol. 268; no. 26; pp. 19173 - 19176
Main Authors OTTLINGER, M. E, PUKAC, L. A, KARNOVSKY, M. J
Format Journal Article
LanguageEnglish
Published Bethesda, MD American Society for Biochemistry and Molecular Biology 15.09.1993
Subjects
Animals
Aorta - enzymology
Biological and medical sciences
Calcium-Calmodulin-Dependent Protein Kinases
Cell cycle, cell proliferation
Cell physiology
Cells, Cultured
Chromatography, Ion Exchange
Enzyme Activation - drug effects
Epidermal Growth Factor - pharmacology
Fundamental and applied biological sciences. Psychology
Heparin - pharmacology
Immunoblotting
Kinetics
Molecular and cellular biology
Muscle, Smooth, Vascular - drug effects
Muscle, Smooth, Vascular - enzymology
Myelin Basic Protein - metabolism
Protein Kinase Inhibitors
Protein Kinases - isolation & purification
Protein Kinases - metabolism
Rats
Tetradecanoylphorbol Acetate - pharmacology
Cell proliferation
Enzyme
Blood vessel
Anticoagulant
Heparin
Inhibition
Myocyte
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Summary:Heparin is potently antiproliferative for vascular smooth muscle cells in vivo and in vitro, inhibiting early proto-oncogene expression and blocking proliferation in the G1 phase of the cell cycle. The mitogen-activated protein kinase (MAPK) family of serine- and threonine-specific kinases is activated in response to a wide range of mitogenic and other factors and is a key intermediate in cell signaling. We found that heparin inhibits activation of MAPK in response to fetal calf serum and phorbol 12-myristate 13-acetate, but not epidermal growth factor, revealing heparin-sensitive and -insensitive pathways of MAPK activation. This report tentatively links suppression of early proto-oncogene expression and inhibition of cellular proliferation by heparin with inhibition of a mitogenically relevant kinase in living cells.
ISSN:0021-9258
1083-351X
DOI:10.1016/S0021-9258(19)36492-0