Nicotinamide analogs and DNA-damaging agents deplete thyroid hormone receptor and c-erbA mRNA levels in pituitary GH1 cells.
Incubation of pituitary GH1 cells with N'-methylnicotinamide, nicotinamide and 3-acetylpyridine which inhibit nuclear ADP-ribosylation and/or the cellular concentration of its substrate NAD+ reduced the amount of nuclear thyroid hormone receptors in a time- and dose-dependent manner without altering the affinity of the receptors for the hormone. A transient activation of poly(ADP-ribose)polymerase by methyl methanesulfonate, ultraviolet irradiation or spermine caused a rapid depletion of cellular NAD+ content and was followed by a strong inhibition of ADP-ribosylation. These agents also produced a very rapid and marked reduction of receptor numbers. The decrease of receptors caused by the different compounds is not secondary to a generalized inhibition of protein synthesis or to an alteration in hormone availability. The abundance of c-erbA alpha and beta mRNAs, which encode thyroid hormone receptors, was reduced in cells treated with the compounds that decrease receptor number, thus suggesting that this effect is caused by a decrease in the expression of c-erbA genes.
Sanchez-Pacheco
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Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Perez
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Villa
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Pascual
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Aranda
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D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D004249:DNA Damage; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D009243:NAD / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*
D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011518:Proto-Oncogene Proteins; D011725:Pyridines; D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; C010835:3-acetylpyridine; D009243:NAD; D000246:Adenosine Diphosphate Ribose; D009536:Niacinamide; D011065:Poly(ADP-ribose) Polymerases; C008472:N-methylnicotinamide