Mechanism of down-regulation of L-type Ca(2+) channel in the proliferating smooth muscle cells of rat aorta.
The mechanism of down-regulation of L-type Ca(2+) 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 alpha(1C) subunit of L-VOC. At confluence on day 8, BrdU incorporation decreased, and the cells up-regulated alpha(1C) subunit mRNA, expressed alpha(1C) subunit protein at cell periphery, and responded to K(+) depolarization. Treating the proliferating cells on day 3 with serum-free media or 10 microM PD98059, a MAP kinase kinase inhibitor, for 2 days induced the expression of alpha(1C) subunit protein and the responsiveness to K(+) depolarization. However, the serum starvation, but not PD98059, decreased the BrdU incorporation and increased the alpha(1C) 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.
Ihara
Eikichi
E
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.
Hirano
Katsuya
K
Hirano
Mayumi
M
Nishimura
Junji
J
Nawata
Hajime
H
Kanaide
Hideo
H
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism*; D002452:Cell Count; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D015536:Down-Regulation; D005419:Flavonoids / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D011188:Potassium / Q000737:chemistry / Q000494:pharmacology; D021122:Protein Subunits; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D020746:Calcium Channels, L-Type; D016895:Culture Media, Serum-Free; D005419:Flavonoids; D007211:Indoles; D021122:Protein Subunits; D012333:RNA, Messenger; D001973:Bromodeoxyuridine; D011188:Potassium; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; C000543:cyclopiazonic acid