Effect of iron-chelating agents on inhibitors of ribonucleotide reductase.

Effect of iron-chelating agents on inhibitors of ribonucleotide reductase.
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DOI:
10.1016/0006-2952(81)90043-5
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发表时间:
1981-05
影响因子:
5.8
通讯作者:
J. G. Cory;L. Lasater;A. Sato
J. G. Cory;L. Lasater;A. Sato
中科院分区:
医学2区
文献类型:
--
作者:
J. G. Cory;L. Lasater;A. Sato

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Ehrlich肿瘤细胞的核苷酸还原酶可被羟基脲(HU)、胍(GZ)、吡唑咪唑(IMPY)、1-甲酰异喹啉缩氨基硫脲(IQ)、4-甲基-5-氨基异喹啉缩氨基硫脲(MAIQ)抑制。肌苷和5‘-脱氧肌苷的二醛。在不影响还原酶活性的EDTA、去雄醛或8-羟基喹啉(8-HQ)存在下,HU、GZ和IMPY对还原酶的抑制作用更强。EDTA,Desferal或8-HQ与核苷二醛衍生物联合使用不影响这些化合物的抑制作用。然而,这些铁络合剂与MAIQ和IQ结合后,逆转了MAIQ和IQ引起的抑制作用。这些数据表明,哺乳动物核糖核苷酸还原酶的非血红素含铁成分的抑制剂可以根据它们对铁络合剂存在的反应进行细分。
Ribonucleotide reductase from Ehrlich tumor cells is inhibited by hydroxyurea (HU), guanazole (GZ), pyrazolo-imidazole (IMPY), 1-formylisoquinoline thiosemicarbazone (IQ), 4-methyl-5-aminoisoquinoline thiosemicarbazone (MAIQ). and the dialdehydes of inosine and 5′-deoxyinosine. In the presence of EDTA, desferal, or 8-hydroxyquinoline (8-HQ) at a concentration that did not affect reductase activity, HU, GZ and IMPY more effectively inhibited the reductase. EDTA, desferal, or 8-HQ in combination with the nucleoside dialdehyde derivatives did not affect the inhibition caused by these compounds. The combination of these iron-chelating agents with MAIQ and IQ, however, reversed the inhibition caused by MAIQ and IQ. These data indicate that the inhibitors of the nonheme iron-containing component of mammalian ribonucleotide reductase can be subclassified, based on their response to the presence of iron-chelating agents.