Ueki S, Takagi J, Kobayashi Y, Sato F, Saito Y
Department of Biological Sciences, Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
J Cell Physiol. 1999 Jan;178(1):63-8. doi: 10.1002/(SICI)1097-4652(199901)178:1<63::AID-JCP8>3.0.CO;2-J.
We report here that the 12-lipoxygenase metabolite of arachidonic acid, 12-hydroxy-5Z, 8Z, 10E, 14Z, eicosatetraenoic acid (12-HETE), stimulates cAMP production in human fibroblasts among various cultured cell lines tested. Although 12-HETE seemed to stimulate the phospholipase C (PLC)-protein kinase C (PKC) system, inhibitors against PLC and PKC did not reduce the cAMP production induced by 12-HETE, indicating that the activation of PLC-PKC system is not positively coupled with the stimulation of cAMP production. On the other hand, the cAMP production induced by 12-HETE was dependent on the Ca2+/calmodulin system in the cells. The results suggest that 12-HETE specifically stimulates Ca2+/calmodulin-dependent adenylyl cyclase to increase cAMP level in the fibroblasts.
我们在此报告,在测试的各种培养细胞系中,花生四烯酸的12-脂氧合酶代谢产物12-羟基-5Z,8Z,10E,14Z-二十碳四烯酸(12-HETE)可刺激人成纤维细胞中的cAMP生成。尽管12-HETE似乎刺激磷脂酶C(PLC)-蛋白激酶C(PKC)系统,但针对PLC和PKC的抑制剂并未降低12-HETE诱导的cAMP生成,这表明PLC-PKC系统的激活与cAMP生成的刺激未呈正相关。另一方面,12-HETE诱导的cAMP生成取决于细胞中的Ca2+/钙调蛋白系统。结果表明,12-HETE特异性刺激Ca2+/钙调蛋白依赖性腺苷酸环化酶以增加成纤维细胞中的cAMP水平。