Shah B H
Department of Physiology and Pharmacology, Aga Khan University, Karachi, Pakistan.
Adv Exp Med Biol. 1997;419:93-7. doi: 10.1007/978-1-4419-8632-0_11.
Cholera toxin (CT) catalyses ADP-ribosylation of the alpha-subunit of stimulatory protein (Gs) leading to stimulation of adenylyl cyclase and elevated intracellular cAMP. Persistent treatment (24-48 h) of C6 glioma cells with cholera toxin (100 ng/ml) caused marked downregulation of Gs alpha (75-80%) which could not be mimicked by dibutyryl cAMP (1 mM) and forskolin (10 microM) over the same time periods suggesting that CT-mediated Gs alpha downregulation is independent of cAMP production. However, CT increased the expression of Gq/11 alpha proteins at 24 and 48 h of treatment. The increase in mRNA levels of Gq/11 alpha proteins preceded the increase in Gq/11 proteins. Such stimulatory effects of CT were mimicked by forskolin and dibutyryl-cAMP. These results suggest that CT-mediated downregulation of Gs alpha is independent of cAMP but CT upregulates the expression of Gq/11 alpha proteins in a cAMP-dependent manner.
霍乱毒素（CT）催化刺激性蛋白（Gs）的α亚基的ADP核糖基化，导致腺苷酸环化酶的激活和细胞内cAMP水平升高。用霍乱毒素（100 ng/ml）对C6胶质瘤细胞进行持续处理（24 - 48小时）会导致Gsα明显下调（75 - 80%），在相同时间段内，二丁酰cAMP（1 mM）和福斯可林（10 μM）无法模拟这种下调，这表明CT介导的Gsα下调与cAMP产生无关。然而，在处理24小时和48小时时，CT增加了Gq/11α蛋白的表达。Gq/11α蛋白的mRNA水平升高先于Gq/11蛋白的增加。福斯可林和二丁酰 - cAMP可模拟CT的这种刺激作用。这些结果表明，CT介导的Gsα下调与cAMP无关，但CT以cAMP依赖的方式上调Gq/11α蛋白的表达。
