REGULATION OF STEROL SYNTHESIS IN CULTURED-CELLS BY OXYGENATED DERIVATIVES OF CHOLESTEROL
REGULATION OF STEROL SYNTHESIS IN CULTURED-CELLS BY OXYGENATED DERIVATIVES OF CHOLESTEROL
复制标题
DOI：
10.1002/jcp.1040850408
复制
发表时间：
1975-01-01
影响因子：
5.6
通讯作者：
CHEN, HW
中科院分区：
文献类型：
--
作者：
KANDUTSCH, AA;CHEN, HW
体内肝脏中的甾醇合成是在3-羟基-3-甲基戊二酰辅酶A还原酶催化的反应部位通过反馈系统调节的，该反馈系统被认为涉及胆固醇或其一种或多种代谢产物。喂饲胆固醇会抑制酶的合成，但酶的失活似乎先于合成的抑制。纯化的外源性胆固醇不抑制培养的小鼠肝细胞和L细胞成纤维细胞的甾醇合成。然而，通过在7、20、22或25位引入酮或羟基而产生的胆固醇的衍生物通过特别抑制HMG辅酶A还原酶的活性来有效地抑制固醇的合成。由于这种特殊的作用，一种抑制生长的类固醇与L细胞长时间孵育会导致细胞类固醇的耗尽。然后，培养物停止生长，细胞死亡，除非在培养液中提供适当的类固醇或类固醇前体。抑制性甾醇、25-羟基胆固醇和7-酮胆固醇似乎是通过与饱和细胞受体的特定相互作用而被L细胞摄取的。L细胞对胆固醇的吸收似乎是通过一个不同的过程--可能是通过物理扩散。
Sterol synthesis in liver in vivo is regulated at the site of the reaction catalyzed by 3‐hydroxy‐3‐methylglutaryl‐CoA reductase through a feedback system thought to involve either cholesterol or one or more of the products of its metabolism. Cholesterol feeding results in repression of the synthesis of the enzyme, but inactivation of the enzyme seems to precede repression of its synthesis. Sterol synthesis in cultured mouse liver cells and in L cell fibroblasts is not inhibited by purified exogenous cholesterol. However, derivatives of cholesterol produced by the introduction of a ketone or hydroxyl function in the 7, 20, 22 or 25 positions effectively inhibit sterol synthesis by specifically depressing the level of HMG CoA reductase activity. As a result of this specific effect prolonged incubation of an inhibitory sterol with growing L cells results in depletion of cellular sterol. Growth of the culture then ceases and the cells die unless an appropriate sterol or a sterol precursor is supplied in the medium. The inhibitory sterols, 25‐hydroxycholesterol and 7‐ketocholesterol appear to be taken up by L cells through processes that involve their specific interactions with saturable cellular receptors. The uptake of cholesterol by L cells appears to be by a different process — possibly through physical diffusion.