Results
Motoko
Department
University
Shibanuma,
of Cancer
of Tokyo,
Toshio
Cell Research,
Kuroki,
Institute
Minato-ku,
and Kiyoshi
of Medical
Tokyo 108,
Nose2
Science,
Japan
Shirokanedai,
Abstract
Transforming growth factor $ (TGF-$1) and H202 both inhibited DNA synthesis of mouse osteoblastic (MC3T3)
cells in the late G1 phase of the cell cycle. TGF-$1 stimulated cells to release H2O2 in the late G1 phase,
but not in the G0 phase, even though TGF-fl1 receptors were present in both phases. The inhibition of DNA
synthesis caused by TGF-$1 was partly decreased by the
addition
of catalase.
TGF-fl1
and H202
proteins
increased
with
the
phosphorylation
of the same
a molecular
weight of 30,000 in cells in the late G1 phase, and the increase by TGF-$1 was abolished at least partly by catalase. The results suggest that H2O2 is one of the mediators of inhibition of DNA synthesis by TGF-1. Introduction TGF-f13 is a multifunctional polypeptide that regulates a wide variety of biological responses. It has profound effects on the processes of development, cellular growth, wound repair, and carcinogenesis (1-3). In vitro studies showed that, in general, it inhibits growth of epithelial cells in the late G1 phase ofthe cell cycle (4, 5) and either stimulates or inhibits the growth of mesenchymal cells depending on the cell type, the conditions of culture, and the presence or absence of other growth factors (I). Controversial results have been reported about the effects of TGF-$ on osteoblastic cells (6, 7). The mechanisms by which TGF-fl1 induces these various responses of cells are now being investigated intensively. Howe et a!. (8, 9) proposed the involvement of both G protein-dependent and -independent pathways as signals of TGF-/31 action. Enhanced c-jun expression was suggested to be an early response to TGF-fl1 (10), although its biological importance is not clear. TGF-1 is known to modulate the expression of a variety of cellular genes. One major site of its action is the cellular matrix, where it inhibits transcription of matrix-degrading enzymes and enhances the synthesis of matrix protein (1115). In normal rat kidney cells, the inhibition of growth

上一页下一页