Differentiation of 3T3-L1 pre-adipocytes induced by inhibitors of poly(ADP-ribose) polymerase and by related noninhibitory acids.
To analyze a possible involvement of ADP-ribosylation reactions in 3T3-L1 pre-adipocyte differentiation. ADP-ribosyltransferase activities is permeabilized cells as well as endogenous amounts of protein-bound mono- and poly(ADP-ribose) residues were determined. Also, in vivo labeling with [3H]adenosine of ADP-ribose residues linked to high-mobility-group (HMG) proteins was performed. As an additional probe, the effects of ADP-ribosylation inhibitors and non-inhibitory analogs were studied. Basal and total poly(ADP-ribose) polymerase activities markedly increased prior to the appearance of the differentiation marker glycerol-3-phosphate dehydrogenase. Despite these apparent changes in activity, however, neither protein-bound poly(ADP-ribose) residue nor mono(ADP-ribosyl) groups in histones, nor the NAD content, changed significantly under these conditions. Furthermore, although HMG protein-associated [3H]ADP-ribose was reduced in differentiating [3H]adenosine-labeled cells, the data suggest altered precursor pool labeling rather than a specific decrease in ADP-ribosylated HMG proteins. Non-participation of ADP-ribosylation reactions in 3T3-L1 differentiation is further supported by experiments with inhibitors and non-inhibitory analogs. Benzamide at 0.3-3 mM per se without effect on differentiation, was able to induce specific gene expression when combined with insulin (10(-12)-10(-7) M). Similar effects were seen with benzoate as well as with nicotinamide, 3-aminobenzamide and their corresponding acids. The data indicate that benzamide and analogs have profound effects on chromatin functions that are not mediated by ADP-ribosylation reactions.
Janssen
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OE
Institut für Physiologische Chemie, Universität Hamburg, Federal Republic of Germany.
Hilz
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D036002:ADP Ribose Transferases; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D019817:Benzoic Acid; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D006609:High Mobility Group Proteins / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D009243:NAD / Q000378:metabolism; D009536:Niacinamide / Q000494:pharmacology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism
D001549:Benzamides; D001565:Benzoates; D004791:Enzyme Inhibitors; D006609:High Mobility Group Proteins; D007328:Insulin; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009243:NAD; D000246:Adenosine Diphosphate Ribose; D009536:Niacinamide; C037689:benzamide; D019817:Benzoic Acid; D005993:Glycerolphosphate Dehydrogenase; D036002:ADP Ribose Transferases; D011065:Poly(ADP-ribose) Polymerases