Gomez-Muñoz A, Hales P, Brindley D N
Department of Biochemistry, University of Alberta, Edmonton, Canada.
Biochem J. 1991 May 15;276 ( Pt 1)(Pt 1):209-15. doi: 10.1042/bj2760209.
Oleate, linoleate, linolenate, arachidonate and eicosapentaenoate, but not myristate, palmitate and stearate, stimulated glycogen phosphorylase activity by 2-8-fold when added to cultured rat hepatocytes. Addition of BSA or Ca2- to the incubation medium decreased the stimulating effects of the unsaturated fatty acids. The combination of oleate or linolenate, with corticosterone, testosterone or estradiol produced synergistic stimulations of phosphorylase activity. The stimulation of glycogen phosphorylase activity by linolenate was inhibited by staurosporine or sphingosine. Staurosporine (80 nM) alone also decreased basal phosphorylase activities by about 60%. The results show that unsaturated fatty acids can be used as model agonists to stimulate phosphorylase activity by a mechanism that probably involves protein kinase C. On the basis of the fatty acid: BSA ratios used, this stimulation should only occur in vivo at high fatty acid concentrations when accompanied by hypoalbuminaemia.
油酸、亚油酸、亚麻酸、花生四烯酸和二十碳五烯酸,但肉豆蔻酸、棕榈酸和硬脂酸则不然,当添加到培养的大鼠肝细胞中时,可使糖原磷酸化酶活性提高2至8倍。向孵育培养基中添加牛血清白蛋白(BSA)或钙离子(Ca2+)会降低不饱和脂肪酸的刺激作用。油酸或亚麻酸与皮质酮、睾酮或雌二醇联合使用可产生对磷酸化酶活性的协同刺激作用。亚麻酸对糖原磷酸化酶活性的刺激作用受到星形孢菌素或鞘氨醇的抑制。单独使用星形孢菌素(80 nM)也可使基础磷酸化酶活性降低约60%。结果表明,不饱和脂肪酸可作为模型激动剂,通过可能涉及蛋白激酶C的机制来刺激磷酸化酶活性。根据所使用的脂肪酸与牛血清白蛋白的比例,这种刺激作用仅在体内脂肪酸浓度高且伴有低白蛋白血症时才会发生。