Regulation of fos and jun immediate-early genes by redox or metabolic stress in cardiac myocytes.
Regulation of fos and jun immediate-early genes by redox or metabolic stress in cardiac myocytes.
复制标题
心肌细胞氧化还原或代谢应激对 fos 和 jun 立即早期基因的调节。
DOI：
10.1161/01.res.74.4.679
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发表时间：
1994
影响因子：
20.1
通讯作者：
Bishopric,NH
中科院分区：
文献类型：
--
作者：
Webster,KA;Discher,DJ;Bishopric,NH
我们以前已经证明了协调诱导c-fos，c-jun，jun B，和jun D在心肌细胞暴露于缺氧2至4小时。这些转录物的诱导发生在细胞内ATP的任何显著损失之前。在本研究中，通过比较缺氧与代谢抑制剂氰化物、脱氧葡萄糖和氰化物组合以及碘乙酸的作用，研究了调节即刻早期基因诱导的信号的来源。氰化物是一种氧化代谢抑制剂，在两种条件下都能密切模拟缺氧的代谢效应，消除氧消耗，增加乳酸产生，ATP水平下降最小。与缺氧相比，氰化物介导的fos和jun转录本的短暂小诱导遵循不同的时间过程。氰化物和脱氧葡萄糖的组合导致乳酸产生以及呼吸抑制，ATP迅速下降到对照水平的20%。细胞内ATP的损失，其次是四倍诱导的c-fos和c-jun与jun B和jun D转录水平的微小变化。类似地，碘乙酸导致ATP的主要（90%）损失和不可逆的细胞损伤，如通过肌酸磷酸激酶的泄漏和膜花生四烯酸的损失所测量的; ATP损失之后是c-fos、c-jun和jun B转录物的五倍至七倍诱导。（250字处删节）
We have previously demonstrated coordinate inductions of c-fos, c-jun, jun B, and jun D in cardiac myocytes exposed to hypoxia for 2 to 4 hours. Induction of these transcripts occurred before any significant loss of intracellular ATP. In the present study, the origin of the signal(s) that regulates immediate-early gene induction was investigated by comparing the effects of hypoxia with those of the metabolic inhibitors cyanide, deoxyglucose and cyanide combined, and iodoacetic acid. Cyanide, an inhibitor of oxidative metabolism, closely mimicked the metabolic effects of hypoxia, with elimination of oxygen consumption, increased lactate production, and minimal decline in ATP levels under both conditions. Compared with hypoxia, cyanide mediated small transient inductions of fos and jun transcripts that followed a different time course. The combination of cyanide and deoxyglucose resulted in inhibition of lactate production as well as respiration, and ATP dropped rapidly to 20% of control levels. The loss of intracellular ATP was followed by fourfold inductions of c-fos and c-jun with minor changes in jun B and jun D transcript levels. Similarly, iodoacetic acid caused a major (90%) loss of ATP and irreversible cell damage as measured by leakage of creatine phosphokinase enzyme and loss of membrane arachidonic acid; ATP loss was followed by fivefold to sevenfold inductions of c-fos, c-jun and jun B transcripts.(ABSTRACT TRUNCATED AT 250 WORDS)