Response of adrenal tumor cells to adrenocorticotropin: site of inhibition by cytochalasin B.
Response of adrenal tumor cells to adrenocorticotropin: site of inhibition by cytochalasin B.
复制标题
肾上腺肿瘤细胞对促肾上腺皮质激素的反应：细胞松弛素 B 的抑制位点。
DOI：
10.1021/bi00633a021
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发表时间：
1977
期刊：
影响因子：
2.9
通讯作者：
P. Hall
中科院分区：
文献类型：
--
作者：
J. Mrotek;P. Hall
检查细胞松弛素B抑制小鼠肾上腺肿瘤细胞（Y-1）对促肾上腺皮质激素（ACTH）的类固醇生成反应的能力有两个目的：考虑抑制剂的特异性并确定它在类固醇生成途径中的哪个点起作用。细胞松弛素B不抑制蛋白质合成或转运[3 H]-胆固醇进入细胞，也不改变ATP的总细胞浓度。与以前的证据一起，这表明观察到的细胞松弛素的作用在这些细胞中是相对特异的。细胞松弛素抑制ACTH产生的[3 H]胆固醇转化为20 α-[3 H]二氢孕酮（20 α-羟基孕甾-4-烯-3-酮：Y-1细胞中类固醇途径的主要产物）的增加，但不抑制分别由Y-1细胞和牛肾上腺的线粒体和纯化酶制剂将胆固醇转化为双烯醇酮。细胞松弛素不抑制双烯醇酮向20 α-二氢孕酮的转化，但显示抑制由ACTH作用引起的[3 H]胆固醇向线粒体的转运增加。这些发现表明细胞松弛素在胆固醇进入细胞后和在线粒体中进行侧链切割之前起作用。鉴于细胞松弛素对微丝的已知作用，有人提出，这些细胞器是必要的胆固醇的线粒体裂解酶的运输和ACTH（和环AMP）的至少一个效果施加在这个运输过程中。细胞松弛素的作用的特异性被认为与这一结论有关。
The ability of cytochalasin B to inhibit the steroidogenic response of mouse adrenal tumor cells (Y-1) to adrenocorticotropin (ACTH) was examined with two aims: to consider the specificity of the inhibitor and to determine at what point(s) in the steroidogenic pathway it acts. Cytochalasin B did not inhibit protein synthesis or transport of [3H]-cholesterol into the cells nor did it alter total cell concentration of ATP. Together with previous evidence, this suggests that the effects of cytochalasin observed are relatively specific in these cells. Cytochalasin inhibits the increase in conversion of [3H]cholesterol to 20alpha-[3H]dihydroprogesterone (20alpha-hydroxypregn-4-en-3-one: a major product of the steroid pathway in Y-1 cells) produced by ACTH but does not inhibit conversion of cholesterol to pregnenolone by mitochondrial and purified enzyme preparations from Y-1 cells and bovine adrenal, respectively. Cytochalasin does not inhibit the conversion of pregnenolone to 20alpha-dihydroprogesterone but was shown to inhibit increased transport of [3H]cholesterol to mitochondria resulting from the action of ACTH. These findings indicate that cytochalasin acts after cholesterol has entered the cells and before it is subjected to side-chain cleavage in mitochondria. In view of the known action of cytochalasin on microfilaments, it is proposed that these organelles are necessary for the transport of cholesterol to the mitochondrial cleavage enzyme and that at least one effect of ACTH (and cyclic AMP) is exerted upon this transport process. The specificity of the effects of cytochalasin is considered in relation to this conclusion.