Regulation of liver zinc metabolism and metallothionein by cAMP, glucagon and glucocorticoids and suppression of free radicals by zinc.
Regulation of liver zinc metabolism and metallothionein by cAMP, glucagon and glucocorticoids and suppression of free radicals by zinc.
复制标题
cAMP、胰高血糖素和糖皮质激素调节肝脏锌代谢和金属硫蛋白，并通过锌抑制自由基。
DOI：
10.1007/978-3-0348-6784-9_56
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Coppen,DE
中科院分区：
文献类型：
--
作者：
Cousins,RJ;Coppen,DE
调节金属硫蛋白的合成和伴随的锌代谢动力学的变化的影响，由二丁酰cAMP，肾上腺素，胰高血糖素和地塞米松在完整的大鼠和分离的大鼠肝实质细胞。肝脏金属硫蛋白水平升高了许多倍，并直接相关的短暂低锌血症后产生的这些激素或Bt 2cAMP管理。孵育单层培养的肝细胞与这些代理引起的变化，迅速采取up 65锌2+和缓慢65锌2+交换，并增加金属硫蛋白水平高达7倍。使用32 P标记的寡核苷酸，对应于作为杂交探针的金属硫蛋白基因的21个碱基的序列，金属硫蛋白mRNA水平被发现由每个激素和cAMP在分离的肝细胞和完整的大鼠增加。这表明除了金属和糖皮质激素外，金属硫蛋白基因表达还受cAMP调节。由叔丁基过氧化氢或3-甲基吲哚引起的离体肝细胞的自由基损伤增加了丙二醛的产生，这可以通过向培养基中加入Zn 2+来减少。这表明锌的摄取影响脂质过氧化的程度。使用电子自旋共振自旋捕获技术表明，锌也减少了自由基的形成，由分离的肝细胞。肝细胞中金属硫蛋白的浓度似乎与锌的细胞功能有关，并通过cAMP水平和糖皮质激素的变化由胰高血糖素协调调节。
Regulation of metallothionein synthesis and concomitant changes in the kinetics of zinc metabolism are influenced by dibutyryl cAMP, epinephrine, glucagon and dexamethasone in both intact rats and isolated rat liver parenchymal cells. Liver metallothionein levels were elevated many fold and were directly related to the transient hypozincemia produced following administration of these hormones or Bt2cAMP. Incubation of monolayer cultures of liver cells with these agents caused changes in both rapidly taken up65Zn2+and slow65Zn2+exchange; and increased metallothionein levels up to 7 fold. Using a32P-labeled oligonucleotide, corresponding to a 21 base sequence of the metallothionein gene as a hybridization probe, metallothionein mRNA levels were found to be increased by each hormone and cAMP in isolated liver cells and intact rats. This indicates metallothionein gene expression is regulated by cAMP in addition to metals and glucocorticoids. Free radical damage to isolated liver cells caused by t-butylhydroperoxide or 3-methylindole increased malondialdehyde production which could be reduced by addition of Zn2+to the culture medium. This suggests zinc uptake influenced the extent of lipid peroxidation. Spin-trapping techniques using electron spin resonance showed zinc also reduced free radical formation by the isolated hepatocytes. The concentration of metallothionein in liver cells seems to be related to cellular functions of zinc and coordinately regulated by glucagon through changes in cAMP levels and glucocorticoids.