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重金属和糖皮质激素对HeLa细胞中金属硫蛋白合成的调控。

Regulation of metallothionein synthesis in HeLa cells by heavy metals and glucocorticoids.

作者信息

Karin M, Slater E P, Herschman H R

出版信息

J Cell Physiol. 1981 Jan;106(1):63-74. doi: 10.1002/jcp.1041060108.

DOI:10.1002/jcp.1041060108
PMID:6162854
Abstract

Metallothioneins (MTs) are low molecular weight, cysteine-rich proteins that bind heavy metals. MT induction occurs in liver in response to either heavy metal (Zn++ or Cd++) administration or stress. The synthesis of MT can also be induced by either heavy metals or glucocorticoid hormones in HeLa cells cultured in serum-free medium. Induction of MT by zinc is subject to "desensitization." In contrast, dexamethasone (dex) induction results in a continued elevation in the rate of MT synthesis. The stability of MT is dependent on the availability of metal; consequently, MT induced by dex is degraded much more rapidly (half-life of 11 to 12 hours) than MT induced by elevated zinc levels (half-life of 36 to 38 hours). Removal of either inducer results in biphasic degradation curves, as apothionein and zinc come into balance. In contrast, deinduction kinetics for MT synthesis following removal of the two inducers (zinc and dex) are the same, with a half-life of two and one-half hours. Inhibition of RNA synthesis blocks deinduction after removal of inducer. Induction of MT occurs in a wide variety of species, from blue-green algae to man. This system should provide an excellent model for the comparative biochemistry of regulation of gene expression.

摘要

金属硫蛋白(MTs)是一类低分子量、富含半胱氨酸且能结合重金属的蛋白质。MT的诱导在肝脏中发生,以响应重金属(锌离子或镉离子)的施用或应激。在无血清培养基中培养的HeLa细胞中,MT的合成也可由重金属或糖皮质激素诱导。锌对MT的诱导会产生“脱敏”现象。相比之下,地塞米松(dex)诱导会导致MT合成速率持续升高。MT的稳定性取决于金属的可用性;因此,由dex诱导产生的MT比锌水平升高诱导产生的MT降解得更快(半衰期为11至12小时)(半衰期为36至38小时)。去除任何一种诱导剂都会导致双相降解曲线,因为脱辅基硫蛋白和锌达到平衡。相比之下,去除两种诱导剂(锌和dex)后MT合成的去诱导动力学是相同的,半衰期为两个半小时。RNA合成的抑制会阻断去除诱导剂后的去诱导过程。MT的诱导发生在从蓝藻到人类的各种各样的物种中。这个系统应该为基因表达调控的比较生物化学提供一个极好的模型。

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