RRC ID 43560
著者 Seya K, Kanemaru K, Matsuki M, Hongo K, Kitahara H, Kikuchi H, Oshima Y, Kubohara Y, Okumura K, Motomura S, Furukawa KI.
タイトル Br-DIF-1 accelerates dimethyl sulphoxide-induced differentiation of P19CL6 embryonic carcinoma cells into cardiomyocytes.
ジャーナル Br J Pharmacol
Abstract BACKGROUND AND PURPOSE:Stem cell transplantation therapy is a promising option for treatment of severe ischaemic heart disease. Dimethyl sulphoxide (DMSO) differentiates P19CL6 embryonic carcinoma cells into cardiomyocyte-like cells, but with low differentiation capacity. To improve the degree of this differentiation, we have assessed several derivatives of the differentiation-inducing factor-1 (DIF-1), originally found in the cellular slime mould Dictyostelium discoideum, on P19CL6 cells.
EXPERIMENTAL APPROACH:P19CL6 cells were cultured with each derivative and 1% DMSO for up to 16 days. Differentiation was assessed by measuring the number of beating and non-beating aggregates, and the expression of genes relevant to cardiac tissue. The mechanism of action was investigated using a T-type Ca(2+) channel blocker.
KEY RESULTS:Of all the DIF-1 derivatives tested only Br-DIF-1 showed any effects on cardiomyocyte differentiation. In the presence of 1% DMSO, Br-DIF-1 (0.3-3 µM) significantly and dose-dependently increased the number of spontaneously beating aggregates compared with 1% DMSO alone, by day 16. Expression of mRNA for T-type calcium channels was significantly increased by Br-DIF-1 + 1% DMSO compared with 1% DMSO alone. Mibefradil (a T-type Ca(2+) channel blocker; 100 nM) and a small interfering RNA for the T-type Ca(2+) channel both significantly decreased the beating rate of aggregates induced by Br-DIF-1 + 1% DMSO.
CONCLUSIONS AND IMPLICATIONS:Br-DIF-1 accelerated the differentiation, induced by 1% DMSO, of P19CL6 cells into spontaneously beating cardiomyocyte-like cells, partly by enhancing the expression of the T-type Ca(2+) channel gene.
巻・号 165(4)
ページ 870-9
公開日 2012-2-1
DOI 10.1111/j.1476-5381.2011.01541.x
PMID 21671902
PMC PMC3312485
MeSH Animals Calcium Channel Blockers / pharmacology Calcium Channels, T-Type / physiology* Cell Differentiation / drug effects* Cell Line, Tumor Dimethyl Sulfoxide Gene Expression / drug effects* Hexanones / pharmacology* Mibefradil / pharmacology Mice Myocytes, Cardiac / cytology Myocytes, Cardiac / drug effects* Myocytes, Cardiac / physiology
IF 7.73
引用数 8
WOS 分野 PHARMACOLOGY & PHARMACY
リソース情報
ヒト・動物細胞 P19CL6