Glucosamine enhances platelet-derived growth factor-induced DNA synthesis via phosphatidylinositol 3-kinase pathway in rat aortic smooth muscle cells

• Published in: Atherosclerosis 2001-08, Vol.157 (2), p.341-352
• Main Authors: Sato, Akira, Sasaoka, Toshiyasu, Yamazaki, Katsuya, Nakamura, Norio, Temaru, Rie, Ishiki, Manabu, Takata, Michiyo, Kishida, Mika, Wada, Tsutomu, Ishihara, Hajime, Usui, Isao, Urakaze, Masaharu, Kobayashi, Masashi
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing; Adaptor Proteins, Vesicular Transport; Animals; Aorta - cytology; Aorta - drug effects; Aorta - metabolism; Atherosclerosis; Azaserine - pharmacology; Biological and medical sciences; Bromodeoxyuridine - metabolism; Cardiology. Vascular system; Cells, Cultured; DNA - biosynthesis; DNA synthesis; Dose-Response Relationship, Drug; Drug Synergism; Enzyme Inhibitors - pharmacology; Glucosamine; Glucosamine - pharmacology; Glucose - pharmacology; GRB2 Adaptor Protein; Heart; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Isoenzymes - metabolism; Medical sciences; Mitogen-Activated Protein Kinases - metabolism; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; PDGF; Phosphatidylinositol 3-Kinases - metabolism; Phospholipase C gamma; Phosphorylation - drug effects; Platelet-Derived Growth Factor - pharmacology; Proteins - metabolism; Rats; Receptor, Platelet-Derived Growth Factor beta - metabolism; Shc Signaling Adaptor Proteins; Src Homology 2 Domain-Containing, Transforming Protein 1; Type C Phospholipases - metabolism; Tyrosine - metabolism; Vascular smooth muscle cell
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/S0021-9150(00)00740-1

Vascular smooth muscle cells play a key role in the development of atherosclerosis. Culture of vascular smooth muscle A10 cells with high glucose for 4 weeks enhanced platelet-derived growth factor (PDGF)-induced BrdU incorporation. Since a long period of high glucose incubation was required for the effect, and it was inhibited by co-incubation with azaserine, the role of hexosamine biosynthesis in the development of atherosclerosis in diabetes was studied in A10 cells. Addition of glucosamine to the culture media enhanced PDGF-stimulated BrdU incorporation, and PDGF-induced tyrosine phosphorylation of the PDGF β-receptor was increased by glucosamine treatment. Of the subsequent intracellular signaling pathways, PDGF-induced PDGF β-receptor association with PLCγ was not affected, whereas tyrosine phosphorylation of Shc, subsequent association of Shc with Grb2, and MAP kinase activation were relatively decreased. In contrast, PDGF-induced PDGF β-receptor association with the p85 regulatory subunit of PI3-kinase and PI3-kinase activation were increased by 20% ( P