12: Biochem Biophys Res Commun. 2001 Aug 3;285(5):1237-43.
K252a, an indrocarbazole derivative, causes the membrane of myoblasts to enter a
fusion-capable state.
Hirayama E, Sasao N, Yoshimasu S, Kim J.
Institute of Molecular and Cellular Biology for Pharmaceutical Sciences, Kyoto
Pharmaceutical University, 1, Shichonocho, Misasagi, Yamashina-ku, Kyoto,
607-8412, Japan.
K252a, an indrocarbazole derivative and protein kinase inhibitor, is reported to
promote myogenic differentiation in C2 mouse myoblasts. We examined the effects
of K252a on QM-RSV cells, quail myoblasts transformed with a
temperature-sensitive mutant of Rous sarcoma virus. K252a promoted myotube
formation of QM-RSV cells. Presumptive QM-RSV cells also formed multinucleated
cells when exposed to K252a. However, the expression of myogenin, a muscle
regulatory factor, was not stimulated in the presence of the drug, suggesting
that it promotes membrane fusion but not myogenic differentiation. To confirm
the promotion of membrane fusion by K252a, presumptive C2 cells, which are
strongly resistant to HVJ-mediated cell fusion, were fused by HVJ (Sendai virus)
after K252a treatment. Presumptive C2 cells treated with K252a fused with HVJ,
demonstrating that K252a causes the cells to enter a fusion-capable state. The
amount of membrane cholesterol, a factor that decreases membrane fluidity, fell
in K252a-treated C2 cells. The results suggest that a decrease of membrane
cholesterol is a cause of the change that renders myoblast membrane susceptible
to fusion in the presence of K252a. Copyright 2001 Academic Press.
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