Journal of Cellular Biochemistry

Mechanism of down-regulation of L-type Ca2+ channel in the proliferating smooth muscle cells of rat aorta

Authors

  • Eikichi Ihara,

    1. Division of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582 Japan
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  • Katsuya Hirano,

    1. Division of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582 Japan
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  • Mayumi Hirano,

    1. Division of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582 Japan
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  • Junji Nishimura,

    1. Division of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582 Japan
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  • Hajime Nawata,

    1. Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582 Japan
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  • Hideo Kanaide

    Corresponding author
    1. Division of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582 Japan
    • Division of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
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Abstract

The mechanism of down-regulation of L-type Ca2+ channel (L-VOC) was investigated in rat aortic smooth muscle cells in primary culture. On culture days 3–5, the cells actively incorporated the 5-bromo-2′-deoxy-uridine (BrdU), and did not respond to K+ depolarization nor express α1C subunit of L-VOC. At confluence on day 8, BrdU incorporation decreased, and the cells up-regulated α1C subunit mRNA, expressed α1C subunit protein at cell periphery, and responded to K+ depolarization. Treating the proliferating cells on day 3 with serum-free media or 10 μM PD98059, a MAP kinase kinase inhibitor, for 2 days induced the expression of α1C subunit protein and the responsiveness to K+ depolarization. However, the serum starvation, but not PD98059, decreased the BrdU incorporation and increased the α1C subunit mRNA. It is concluded that the expression of L-VOC is substantially suppressed in the proliferating cells due to two mechanisms; a MAP kinase-mediated post-transcriptional down-regulation and the transcriptional down-regulation by additional mitogenic signals. J. Cell. Biochem. 87: 242–251, 2002. © 2002 Wiley-Liss, Inc.

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