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

Eikichi Ihara, Katsuya Hirano, Mayumi Hirano, Junji Nishimura, Hajime Nawata, Hideo Kanaide

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)242-251
Number of pages10
JournalJournal of Cellular Biochemistry
Volume87
Issue number2
DOIs
Publication statusPublished - Oct 16 2002

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Depolarization
Bromodeoxyuridine
Volatile organic compounds
Smooth Muscle Myocytes
Muscle
Aorta
Rats
Down-Regulation
Cells
Protein Subunits
Cell culture
Messenger RNA
Serum-Free Culture Media
Mitogen-Activated Protein Kinase Kinases
MAP Kinase Kinase 2
Phosphotransferases
Starvation
Serum
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Mechanism of down-regulation of L-type Ca2+ channel in the proliferating smooth muscle cells of rat aorta. / Ihara, Eikichi; Hirano, Katsuya; Hirano, Mayumi; Nishimura, Junji; Nawata, Hajime; Kanaide, Hideo.

In: Journal of Cellular Biochemistry, Vol. 87, No. 2, 16.10.2002, p. 242-251.

Research output: Contribution to journalArticle

Ihara, Eikichi ; Hirano, Katsuya ; Hirano, Mayumi ; Nishimura, Junji ; Nawata, Hajime ; Kanaide, Hideo. / Mechanism of down-regulation of L-type Ca2+ channel in the proliferating smooth muscle cells of rat aorta. In: Journal of Cellular Biochemistry. 2002 ; Vol. 87, No. 2. pp. 242-251.
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