Nitroheterocycle metabolism in mammalian cells. Stimulation of the hexose monophosphate shunt.

Nitroheterocycle metabolism in mammalian cells. Stimulation of the hexose monophosphate shunt.
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哺乳动物细胞中的硝基杂环代谢。

DOI:
10.1016/0006-2952(84)90290-9
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发表时间:
1984
影响因子:
5.8
通讯作者:
Biaglow,JE
Biaglow,JE
中科院分区:
医学2区
文献类型:
--
作者:
Varnes,ME;Tuttle,SW;Biaglow,JE

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当与小鼠艾氏腹水细胞或人A549肺癌细胞体外孵育时,米索硝唑、SR-2508、呋喃西林和其他硝基杂环刺激从[1-14C]葡萄糖释放14CO2,但不刺激从[6-14C]葡萄糖释放14CO2。这证明硝基化合物激活了己糖单磷酸分流,并且证明这些细胞系中硝基还原的重要途径是从NADPH依赖性细胞色素还原酶到硝基的电子转移。在有氧和无氧条件下均会刺激分流活性。对于无过氧化氢酶的艾氏细胞,有氧作用大于无氧作用,表明NADPH在有氧条件下通过GSH过氧化物酶和还原酶用于还原H2O2,以及用于单电子硝基还原。所测试的几种化合物刺激从[2-14C]葡萄糖以及从[1-14C]葡萄糖释放 14 CO 2 。这表明,在硝基药物存在的情况下,细胞对 NADPH 的需求足以引起戊糖磷酸的回收。回收可能会减少核酸合成所需的核糖-5-P的可用性,这可以部分解释在细胞与硝基化合物长时间有氧孵育时观察到的DNA合成抑制。呋喃西林从厌氧A549细胞悬浮液中消失的速率与14 CO 2 释放速率的比较表明,该细胞系中的药物减少几乎完全由需要NADPH的酶催化。
Misonidazole, SR-2508, nitrofurazone and other nitroheterocycles stimulated release of14CO2from [1-14C]glucose but not from [6-14C]glucose when incubated with mouse Ehrlich ascites cells or human A549 lung carcinoma cellsin vitro. This demonstrated that the nitro compounds activated the hexose monophosphate shunt and is evidence that an important pathway of nitro reduction in these cell lines is electron transfer from NADPH-dependent cytochromecreductase to the nitro group. Shunt activity was stimulated under both aerobic and anaerobic conditions. For catalase-free Ehrlich cells, aerobic effects were greater than anaerobic, indicating that NADPH was used for reduction of H2O2, via GSH peroxidase and reductase, as well as for one-electron nitro reduction, under aerobic conditions. Several of the compounds tested stimulated14CO2release from [2-14C]glucose as well as from [1-14C]glucose. This shows that the cellular requirement for NADPH, in the presence of nitro drug, was great enough to cause recycling of pentose phosphates. Recycling could decrease the availability of ribose-5-P needed for nucleic acid synthesis, which could partly explain the inhibition of DNA synthesis observed upon prolonged aerobic incubation of cells with nitro compounds. Comparison of the rate of disappearance of nitrofurazone from anaerobic A549 cell suspensions with the rate of14CO2release suggests that the drug reduction in this cell line was catalyzed almost entirely by NADPH-requiring enzymes.
使用氧化酶电极确定影响艾利希细胞和 1-氯-2, 4-二硝基苯体外产生过氧化氢的因素。
DOI: 10.1016/0006-2952(81)90519-0
发表时间: 1981
影响因子: 5.8
作者:
Schroy,CB;Biaglow,JE
通讯作者: Biaglow,JE
在硝基呋喃存在下,艾利希腹水肿瘤细胞中的电子转移。
DOI: --
发表时间: 1976
影响因子: 5.8
作者:
J. Biaglow;J. Biaglow;O. Nygaard;O. Nygaard;C. Greenstock
通讯作者: C. Greenstock
硝基咪唑类药物作为放射增敏剂的临床经验。
DOI: --
发表时间: 1982
期刊: International Journal of Radiation Oncology, Biology, Physics
影响因子: --
作者:
S. Dische;M. Saunders;P. Anderson;M. Stratford;A. Minchinton
通讯作者: A. Minchinton
大鼠肺中 NADPH 消耗和混合二硫化物形成与百草枯给药后细胞损伤机制的相关性。
DOI: --
发表时间: 1982
影响因子: 5.8
作者:
P. Keeling;Lewis L. Smith
通讯作者: Lewis L. Smith
缺氧细胞放射增敏药物对细胞氧利用的影响。
DOI: 10.1016/0163-7258(80)90084-4
发表时间: 1980
影响因子: 13.5
作者:
Biaglow,JE
通讯作者: Biaglow,JE