On the mechanism of preadipocyte differentiation. Masking of poly(ADP-ribose) synthetase activity during differentiation of 3T3-L1 preadipocytes.

Differentiation of 3T3-L1 preadipocytes, induced by methylisobutylxanthine (MIX), dexamethasone (DEX), and insulin, produces cells with the morphological and biochemical characteristics of adipocytes. Poly(ADP-ribose) synthetase activity in 3T3-L1 cells treated with MIX, DEX, and insulin underwent an abrupt decrease in activity, remained low for several hours, and then increased; this rise was delayed by readdition of MIX, DEX, and insulin. The drop of synthetase activity represents the earliest alteration of a specific enzyme yet detected during the differentiation of 3T3-L1 cells. Nondifferentiating 3T3-C2 control cells do not exhibit changes in poly(ADP-ribose) synthetase activity when treated with MIX, DEX, and insulin. The transient reduction in poly(ADP-ribose) synthetase activity in 3T3-L1 cells occurred prior to the appearance of the adipocyte phenotype induced by the above agents and was not observed when preparations were assayed in the presence of DNase I. It is evident that poly(ADP-ribose) synthetase activity was masked following treatment with MIX, DEX, and insulin since the synthetase is sensitive to agents that affect the physical properties of DNA. This transient reduction in activity may be an early event in differentiation which reflects changes in chromatin structure.