Holen I, Gordon P B, Seglen P O
Department of Tissue Culture, Norwegian Radium Hospital, Oslo.
Biomed Biochim Acta. 1991;50(4-6):389-92.
Using isolated hepatocytes as a model system we have investigated whether the cyclic nucleotides cAMP and cGMP are involved in the regulation of the autophagic process. The dibutyryl-cyclic nucleotide analogues db-cAMP and db-cGMP both inhibited autophagic sequestration, suggesting that cAMP and cGMP may be of significance for this step. The adenylate cyclase stimulator deacetyl-forskolin both raised the level of intracellular cAMP and reduced sequestration markedly. In contrast, the guanylate cyclase stimulating agent atriopeptin did not affect sequestration although, it effectively elevated, the level of cGMP. Several inhibitors of cyclic nucleotide phosphodiesterases strongly suppressed autophagy and elevated the level of both cAMP and cGMP. However, one inhibitor, milrinone, raised the cAMP level 3-4 x while having no significant effect on cGMP. These results suggest that cAMP may be involved in the control of hepatic autophagy, whereas the role of cGMP, if any, remains unclear.
我们以分离的肝细胞作为模型系统，研究了环核苷酸cAMP和cGMP是否参与自噬过程的调节。二丁酰环核苷酸类似物db - cAMP和db - cGMP均抑制自噬隔离，提示cAMP和cGMP可能在这一步骤中具有重要意义。腺苷酸环化酶刺激剂去乙酰佛司可林既能提高细胞内cAMP水平，又能显著降低自噬隔离。相反，鸟苷酸环化酶刺激剂心房肽虽然有效提高了cGMP水平，但对自噬隔离没有影响。几种环核苷酸磷酸二酯酶抑制剂强烈抑制自噬，并提高了cAMP和cGMP水平。然而，一种抑制剂米力农使cAMP水平提高了3 - 4倍，而对cGMP没有显著影响。这些结果表明，cAMP可能参与肝脏自噬的调控，而cGMP的作用（如果有）仍不清楚。
