Overproduction of S-adenosylmethionine decarboxylase in ethylglyoxal-bis(guanylhydrazone)-resistant mouse FM3A cells.
A variant cell line, termed SAM-1, which overproduced S-adenosylmethionine decarboxylase (AdoMetDC), was isolated by treatment of mouse FM3A cells with N-methyl-N'-nitro-N-nitrosoguanidine and subsequent incubation with ethylglyoxal bis(guanylhydrazone), an inhibitor of the enzyme. The cells were resistant to ethylglyoxal bis(guanylhydrazone), and showed AdoMetDC activity approximately five-times higher than control cells. The rate of AdoMetDC synthesis and the amount of AdoMetDC existing in SAM-1 cells were about five-times those in control cells. The amount of AdoMetDC mRNA existing in SAM-1 cells was five-times more than that in control cells. The amount of 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine, an irreversible inhibitor of AdoMetDC, necessary to inhibit cell growth was also five-times more in SAM-1 cells than in control cells. However, the following were the same in both SAM-1 and control cells; the amount of genomic DNA for AdoMetDC, the size and nucleotide sequence of 5' untranslated region of AdoMetDC mRNA, the deduced amino acid sequence (334 residues) from the nucleotide sequence of AdoMetDC cDNA and the degradation rate (t1/2 = about 4 h) of AdoMetDC. In addition, AdoMetDC mRNA in control cells was slightly more stable than that in SAM-1 cells. The results indicate that the overproduction of AdoMetDC in SAM-1 cells was caused by the increase of AdoMetDC mRNA. The variant cell line is convenient for studying the regulation of AdoMetDC and the physiological function of polyamines.
Suzuki
T
T
Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Sadakata
Y
Y
Kashiwagi
K
K
Hoshino
K
K
Kakinuma
Y
Y
Shirahata
A
A
Igarashi
K
K
D012437:Adenosylmethionine Decarboxylase / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004351:Drug Resistance; D006207:Half-Life; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D051379:Mice; D008935:Mitoguazone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D008969:Molecular Sequence Data; D011073:Polyamines / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D011073:Polyamines; D012333:RNA, Messenger; D008769:Methylnitronitrosoguanidine; C041127:ethylglyoxal bis(guanylhydrazone); D004247:DNA; D012437:Adenosylmethionine Decarboxylase; D008935:Mitoguazone