The in vivo inhibition of mouse brain protein kinase-C by retinoic acid.
The in vivo inhibition of mouse brain protein kinase-C by retinoic acid.
复制标题
视黄酸对小鼠脑蛋白激酶-C 的体内抑制作用。
DOI：
10.1016/0304-3835(86)90052-2
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发表时间：
1986
期刊：
影响因子：
9.7
通讯作者：
Cope,FO
中科院分区：
文献类型：
--
作者：
Cope,FO
脑池内注射全反式视黄酸或[α]-二氟甲基鸟氨酸（DFMO）至9日龄小鼠的脑中，以浓度依赖性方式阻断（90%）佛波酯诱导的鸟氨酸脱羧酶（ODC，EC www.example.com）活性;使用生物学上无效的视黄酸呋喃类似物时，这种抑制作用不明显。以类似的方式，视黄酸降低可溶性蛋白激酶-C（PK-C）活性的60%，以及总EGTA敏感的激酶活性（66%）与质膜。视黄酸诱导的可溶性组分中PK-C活性损失的66%可以通过PK-C向质膜的移位来解释，如通过12-O-[3H]十四烷基佛波醇-13-乙酸酯（TPA）的特异性结合所测量的。DFMO和呋喃维甲酸不能有效改变PK-C活性或TPA与PK-C的结合。然而，在维甲酸的存在下，有一个2.3倍的增加，在特定的[3H] TPA结合在质膜部分，这是3.4倍大于从胞质溶胶中丢失。由于类维生素A不直接影响TPA与PK-C的结合，因此数据表明：（i）维甲酸的存在导致膜中迄今为止隐藏的TPA结合位点暴露，其中这种结合最有可能与膜结构的改变有关;（ii）PK-C的类维生素A依赖性抑制不需要从头ODC诱导，尽管TPA诱导PK-C对于ODC诱导似乎是必要的。
The intracisternal injection of either all-trans-retinoic acid or [α]-difluoromethylornithine (DFMO) into the brain of 9-day-old mice blocked (90%) phorbol ester-induced ornithine decarboxylase (ODC, EC 4.1.1.17) activity in a concentration-dependent fashion; this inhibition was not evident with the use of the biologically impotent furyl analog of retinoic acid. In a similar manner, retinoic acid reduced the soluble protein kinase-C (PK-C) activity by 60% as well as total EGTA-sensitive kinase activity (66%) associated with the plasma membrane. Sixty-six percent of the retinoic acid-induced loss of PK-C activity in the soluble fraction could be accounted for by the translocation of PK-C to the plasma membrane as measured by the specific binding of 12-O-[3H]tetradecanylphorbol-13-acetate (TPA). DFMO and furyl-retinoic acid were not effective in altering PK-C activity or TPA binding to PK-C. In the presence of retinoic acid, however, there was a 2.3-fold increase in specific [3H] TPA binding in the plasma membrane fraction, which was 3.4-fold greater than that lost from the cytosol. Because retinoids do not directly affect TPA binding to PK-C, the data suggest that (i) the presence of retinoic acid results in the exposure of heretofore cryptic TPA-binding sites in the membrane, where this binding is most likely related to the alteration of membrane structure and (ii) de novo ODC induction is not required for retinoid-dependent inhibition of PK-C, although the TPA induction of PK-C appears to be necessary with regard to ODC induction.