Wu G, Lu Z H, Ledeen R W
New Jersey Medical School, UMDNJ, Department of Neurosciences, Newark 07103, USA.
Glycoconj J. 1996 Apr;13(2):235-9. doi: 10.1007/BF00731498.
This study demonstrates modulation by GM1 ganglioside of prostaglandin E1 (PGE1)-induced cAMP formation in Neuro-2a neuroblastoma cells. Pretreatment of the cells with neuraminidase, an enzyme that increases cell surface GM1, resulted in significant elevation of PGE1-induced cAMP formation, as did preincubation of the cells with nmolar concentrations of GM1. Pretreatment with brain ganglioside mixture lacking GM1 had no effect. Cholera toxin B subunit, a specific GM1-binding ligand, inhibited adenylyl cyclase. When the concentration of exogenous GM1 in which the cells were preincubated was increased from nmolar to mu molar levels there was a dose-responsive fall off in cAMP elevation, attributed to progressive inhibition of adenylyl cyclase by increasing GM1. These results are interpreted as indicating modulation of this PGE1 receptor in Neuro-2a cells by plasma membrane-localized GM1 in a structure-specific manner.
本研究证明了神经节苷脂GM1对前列腺素E1(PGE1)诱导的Neuro-2a神经母细胞瘤细胞中环磷酸腺苷(cAMP)形成的调节作用。用神经氨酸酶(一种增加细胞表面GM1的酶)对细胞进行预处理,导致PGE1诱导的cAMP形成显著升高,用纳摩尔浓度的GM1对细胞进行预孵育也有同样效果。用缺乏GM1的脑苷脂混合物进行预处理则没有效果。霍乱毒素B亚单位是一种特异性GM1结合配体,可抑制腺苷酸环化酶。当细胞预孵育的外源性GM1浓度从纳摩尔水平增加到微摩尔水平时,cAMP升高出现剂量依赖性下降,这归因于GM1增加对腺苷酸环化酶的逐渐抑制。这些结果被解释为表明质膜定位的GM1以结构特异性方式调节Neuro-2a细胞中的这种PGE1受体。