Induction of spermidine/spermine N1-acetyltransferase by methylglyoxal bis(guanylhydrazone).
Induction of spermidine/spermine N1-acetyltransferase by methylglyoxal bis(guanylhydrazone).
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甲基乙二醛双（脒腙）诱导亚精胺/精胺 N1-乙酰转移酶。
DOI：
10.1016/0304-4165(85)90192-8
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Persson,L
中科院分区：
文献类型：
--
作者：
Pegg,AE;Erwin,BG;Persson,L
抗肿瘤药物甲基乙二醛双（鸟苷酰腙）被发现是一种竞争性的精酰胺/精胺N1-乙酰转移酶抑制剂，aKi约为8 μM。用这种药物治疗大鼠导致肝脏、肾脏和脾脏中亚精胺/精胺N1-乙酰转移酶总量大幅增加。在80 mg/kg剂量给药后18小时内，使用特异性抗血清测量的总增加量在肝脏中为700倍，在肾脏中为100倍。这种诱导至少部分是由于乙酰转移酶的半衰期显著增加，从15分钟增加到12小时以上。酶量的极大增加很可能压倒直接抑制，并且在用甲基乙二醛双（鸟苷酰腙）处理后，预期会发生由该酶引起的多胺乙酰化的净增加。已知乙酰化多胺被多胺氧化酶快速降解，产生腐胺。直接证据表明，甲基乙二醛双（鸟苷酰腙）处理的大鼠肝脏中腐胺含量的增加有很大一部分是通过诱导乙酰化酶/氧化酶途径发生的。这些结果表明，甲基乙二醛双（鸟苷酰腙）影响细胞多胺水平不仅通过其对S-腺苷甲硫氨酸脱羧酶和二胺氧化酶的抑制作用，但也通过诱导亚精胺/精胺N1-乙酰转移酶。他们还提出了这样的可能性，即在较高剂量下发生的这种酶的巨大增加可能导致甲基乙二醛双（鸟苷酰腙）的非常严重的毒性。
The anti-tumor agent methylglyoxal bis(guanylhydrazone) was found to be a competitive inhibitor of spermide/spermineN1-acetyltransferase with aKiof about 8 μM. Treatment of rats with this drug lead to a very large increase in the total amount of spermidine/spermineN1-acetyltransferase in liver, kidney and spleen. The total increase as measured using a specific antiserum amounted to 700-fold in liver and 100-fold in kidney within 18 h of treatment with 80 mg/kg doses. At least part of this induction was due to a pronounced increased in the half-life of the acetyltransferase which increased from 15 min to more than 12 h. The very large increase in the amount of the enzyme is likely to overwhelm the direct inhibition, and a net increase in the acetylation of polyamine by this enzyme would be expected to occur after treatment with methylglyoxal bis(guanylhydrazone). The acetylated polyamines are known to be rapidly degraded by polyamine oxidase producing putrescine. Direct evidence that a substantial part of the increase in the content of putrescine in the liver of rats treated with methylglyoxal bis(guanylhydrazone) occures via the induction of thie acetylase/oxidase pathway was obtained. These results indicate that methylglyoxal bis(guanylhydrazone) affects cellular polyamine levels not only by means of its inhibitory effect onS-adenosylmethionine decarboxylase and diamine oxidase but also by the induction of spermidine/spermineN1-acetyltransferase. They also raise the possibility that the enormous increse in this enzyme which occurs with higher doses may contribute to the very severe toxicity of methylglyoxal bis(guanylhydrazone).
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影响因子：
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作者：
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通讯作者：
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作者：
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DOI：
--
发表时间：
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期刊：
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影响因子：
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DOI：
--
发表时间：
1981
期刊：
Cancer treatment reports
影响因子：
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作者：
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