TY - JOUR
T1 - Ethanol, Zn2+ and insulin interact as progression factors to enhance DNA synthesis synergistically in the presence of Ca2+ and other cell cycle initiators in fibroblasts
AU - Huang, Jin Sheng
AU - She, Qing Bai
AU - Crilly, Karan S.
AU - Kiss, Zoltan
N1 - Copyright:
Copyright 2004 Elsevier Science B.V., Amsterdam. All rights reserved.
PY - 2000/2/15
Y1 - 2000/2/15
N2 - In serum-starved NIH 3T3 fibroblasts, ethanol (30-80 mM) promoted the effects of insulin and insulin-like growth factor I (IGF-I) on DNA synthesis in a Zn2+-dependent manner. Ethanol and Zn2+ were most effective when added shortly before or after insulin, indicating that all these agents facilitated cell cycle progression. The synergistic effects of ethanol, Zn2+ and insulin (or IGF-I) on DNA synthesis required 1.1-2.3 mM Ca2+, which seemed to act as the cell cycle initiator. When serum-starved cells were pretreated for 2 h with other cell cycle initiators such as 10% (v/v) serum, 50 ng/ml platelet-derived growth factor or 2 ng/ml fibroblast growth factor, subsequent co-treatments with 60 mM ethanol, Zn2+ and insulin for an 18 h period again synergistically increased DNA synthesis. Of the various signal transducing events examined, ethanol stimulated cellular uptake of 45Ca and it enhanced the stimulatory effects of insulin on p70 S6 kinase activity in a Zn2+-dependent manner. In contrast, ethanol inhibited insulin-induced activating phosphorylation of p42/p44 mitogen-activated protein kinases; these inhibitory ethanol effects were prevented by Zn2+. The results show that, in NIH 3T3 fibroblasts, ethanol can promote cell cycle progression in the presence of a cell cycle initiator as well as Zn2+ and insulin (or IGF-I).
AB - In serum-starved NIH 3T3 fibroblasts, ethanol (30-80 mM) promoted the effects of insulin and insulin-like growth factor I (IGF-I) on DNA synthesis in a Zn2+-dependent manner. Ethanol and Zn2+ were most effective when added shortly before or after insulin, indicating that all these agents facilitated cell cycle progression. The synergistic effects of ethanol, Zn2+ and insulin (or IGF-I) on DNA synthesis required 1.1-2.3 mM Ca2+, which seemed to act as the cell cycle initiator. When serum-starved cells were pretreated for 2 h with other cell cycle initiators such as 10% (v/v) serum, 50 ng/ml platelet-derived growth factor or 2 ng/ml fibroblast growth factor, subsequent co-treatments with 60 mM ethanol, Zn2+ and insulin for an 18 h period again synergistically increased DNA synthesis. Of the various signal transducing events examined, ethanol stimulated cellular uptake of 45Ca and it enhanced the stimulatory effects of insulin on p70 S6 kinase activity in a Zn2+-dependent manner. In contrast, ethanol inhibited insulin-induced activating phosphorylation of p42/p44 mitogen-activated protein kinases; these inhibitory ethanol effects were prevented by Zn2+. The results show that, in NIH 3T3 fibroblasts, ethanol can promote cell cycle progression in the presence of a cell cycle initiator as well as Zn2+ and insulin (or IGF-I).
KW - MAP kinase
KW - Mitogenesis
KW - p70 S6 kinase
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U2 - 10.1042/0264-6021:3460241
DO - 10.1042/0264-6021:3460241
M3 - Article
C2 - 10657263
AN - SCOPUS:0034652221
SN - 0264-6021
VL - 346
SP - 241
EP - 247
JO - Biochemical Journal
JF - Biochemical Journal
IS - 1
ER -