Genistein Inhibits Rat Aortic Smooth Muscle Cell Proliferation Through the Induction of p27^<kip1>

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概要

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• Diet is one of the most important factors that influence the risks for cardiovascular diseases. Genistein, an isoflavone found in soy, may benefit the cardiovascular system. Here, we investigated the effect of genistein on platelet-derived growth factor (PDGF)-BB–induced proliferation of primary cultured rat aortic smooth muscle cells (RASMCs). Genistein significantly inhibited 25 ng/ml PDGF-BB–induced RASMC proliferation and [3H]-thymidine incorporation into DNA at 10, 20, and 40 μM. In accordance with these findings, genistein blocked the PDGF-BB–inducible progression through G0/G1 to S phase of the cell cycle in synchronized cells. Western blot analysis showed that genistein not only inhibited phosphorylation of retinoblastoma protein (pRb) and expression of cyclin E, cyclin-dependent kinase (CDK) 2, and proliferating cell nuclear antigen (PCNA) protein, but also inhibited downregulation of cyclin-dependent kinase inhibitor (CKI) p27kip1. However, genistein did not affect p21cip1, CDK4, and cyclin D1 expression or early signal transduction through PDGF beta-receptor, extracellular signal-regulated kinases 1/2 (ERK1/2), Akt, and phospholipase C (PLC) γ1 phosphorylation. These results suggest that genistein inhibits PDGF-BB–induced RASMC proliferation via G0/G1 arrest in association with induction of p27kip1, which may contribute to the beneficial effects of genistein on the cardiovascular system.

• 社団法人 日本薬理学会の論文
• 2008-05-20

著者

• Kim Tack-Joong

  Division of Biological Science and Technology, College of Science and Technology, Institute of Bioma

• Lee Jung-jin

  Coll. Of Pharmacy Chungnam National Univ.

• Yun Yeo-Pyo

  College of Pharmacy, Chungbuk National University

• Kim Tack-joong

  Div. Of Biological Sci. And Technol. Coll. Of Sci. And Technol. Inst. Of Biomaterials Yonsei Univ.

• Yun Yeo-pyo

  Coll. Of Pharmacy Chungbuk National Univ.

• Yun Yeo-pyo

  College Of Pharmacy Research Center For Bioresource And Health Chungbuk National University

• Yun Yeo-pyo

  College Of Pharmacy Chungbuk National University

• LEE Jung-Jin

  College of Pharmacy, Research Center for Bioresource and Health, Chungbuk National University

• YU Ji-Yeon

  College of Pharmacy, Research Center for Bioresource and Health, Chungbuk National University

• Lim Yong

  Research Institute Of Veterinary Medicine Chungbuk National University

• JIN Yong-Ri

  Center for Molecular Medicine, Maine Medical Center Research Institute

• SHEEN Yhun

  College of Pharmacy, Ewha Womans University

• Yu Ji-yeon

  Inst. For Molecular Biology And Genetics Chonbuk National Univ.

• Sheen Yhun

  College Of Pharmacy Ewha Womans University

• Sheen Yhun

  College Of Pharmacy Department Of Pharmacy College Of Pharmacy Ewha Womans University

• Jin Yong-ri

  Center For Molecular Medicine Maine Medical Center Research Institute

• Yun Yeo-pyo

  College Of Pharmacy Cbitrc College Of Pharmacy And Medical Research Center Chungbuk National Univers

• Yun Yeo-pyo

  College Of Pharmacy Cbitrc College Of Pharmacy And Medical Research Center Chungbuk National University

• Kim Tack-joong

  Division Of Biological Science And Technology College Of Science And Technology Yonsei University

• Lee Jung-Jin

  College of Pharmacy, Chungnam National University

• Yun Yeo-Pyo

  College of Pharmacy and Medical Research Center, Chungbuk National University

• KIM Tack-Joong

  Division of Biological Science and Technology and Yonsei-Fraunhofer Medical Device Lab, College of Science and Technology, Yonsei University

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