The enzymes of acetyl-CoA metabolism in differentiating cholinergic (s-20) and noncholinergic (NIE-115) neuroblastoma cells.
Dibutyryl cyclic AMP and butyrate inhibited growth of S-20 (cholinergic) and NIE-115 (adrenergic) neuroblastoma clones. Both these drugs resulted in a parallel increase of choline acetyltransferase and ATP-citrate lyase activities in S-20 neuroblastoma cells. On the other hand, the increase in tyrosine hydroxylase activity in NIE-115 caused by these drugs was not accompanied by a significant change in ATP-citrate lyase activity. Both dibutyryl cyclic AMP and butyrate caused a decrease in fatty acid synthetase activity in both cell lines. The activities of pyruvate dehydrogenase, citrate synthase, choline acetyltransferase, and lactate dehydrogenase in both S-20 and NIE-115 cells were not significantly influenced by the drugs. ATP-citrate lyases from S-20 and NIE-115 had similar kinetic and immunological properties, and their subunits had the same molecular weight as the rat liver enzyme. These data indicate that the differential regulation of ATP-citrate lyase activity in cholinergic and adrenergic cells does not result from the existence of different molecular forms of the enzyme in these cell lines. They also provide further evidence to support the hypothesis that ATP-citrate lyase activity increases during maturation of normal cholinergic neurons and decreases in noncholinergic cells of the brain.
D001275:ATP Citrate (pro-S)-Lyase / Q000378:metabolism; D000105:Acetyl Coenzyme A / Q000378:metabolism*; D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D064429:Fatty Acid Synthases / Q000378:metabolism; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D009374:Neoplasms, Experimental / Q000503:physiopathology; D009447:Neuroblastoma / Q000503:physiopathology*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism
D002087:Butyrates; D011768:Pyruvate Dehydrogenase Complex; D020148:Butyric Acid; D003994:Bucladesine; D000105:Acetyl Coenzyme A; D007770:L-Lactate Dehydrogenase; D002795:Choline O-Acetyltransferase; D064429:Fatty Acid Synthases; D002950:Citrate (si)-Synthase; D001275:ATP Citrate (pro-S)-Lyase; D000109:Acetylcholine