Ganglioside GQ1b-induced terminal differentiation in cultured mouse keratinocytes. Phosphoinositide turnover forms the onset signal.
Ganglioside GQ1b-induced terminal differentiation in cultured mouse keratinocytes. Phosphoinositide turnover forms the onset signal.
复制标题
神经节苷脂 GQ1b 诱导培养的小鼠角质形成细胞的终末分化。
作者：
Y. Yada;Y. Okano;Y. Nozawa
进行了调查，以了解小鼠角质细胞分化是否由神经节苷脂引起。在测试的神经节苷脂中，只有GQ1b，一种含有两个二甲酰基残基的四asialalgangli苷脂，诱导角质细胞分化，通过形成角化包膜，增强转谷氨酰胺酶活性和抑制DNA合成表明。GQ1b刺激后，Ins(1,4,5)P3的质量含量和细胞内Ca2+水平呈时间和剂量依赖性显著增强，而其他神经节苷类没有观察到显著变化，从而表明磷脂酶C激活了角质形成细胞分化的发生。此外，只有GQ1b促进蛋白激酶C （PKC）从细胞质向膜的易位。用H-7抑制PKC或通过长时间用phorbol 12,13-dibutyrate预处理下调该酶，可显著抑制GQ1b诱导的转谷氨酰胺酶活性和谷氨酰胺包膜的形成。这些结果表明，四联神经节苷脂GQ1b通过磷酸肌肽转换在小鼠角质形成细胞中产生初始分化信号，同时也表明PKC激活可能在分化过程的某些尚未确定的阶段起作用。
Investigations were undertaken to see whether mouse keratinocyte differentiation was elicited by gangliosides. Among the gangliosides tested only GQ1b, a tetrasialoganglioside containing two disialosyl residues, induced keratinocyte differentiation, as indicated by the formation of cornified envelopes, enhancement of transglutaminase activity and suppression of DNA synthesis. Upon stimulation with GQ1b the mass content of Ins(1,4,5)P3 and the intracellular Ca2+ levels were markedly enhanced in a time- and dose-dependent manner, whereas no significant changes were observed with other gangliosides, thereby indicating activation of phospholipase C for the onset of keratinocyte differentiation. Furthermore, only GQ1b promoted the translocation of protein kinase C (PKC) from cytosol to membrane. Inhibition of PKC with H-7 or down-regulation of the enzyme by prolonged pre-treatment with phorbol 12,13-dibutyrate greatly suppressed transglutaminase activity and formation of cornified envelopes induced by GQ1b. These results demonstrate that the tetrasialoganglioside GQ1b generates the initial differentiation signal in mouse keratinocytes through phosphoinositide turnover, and also suggest that PKC activation may act at certain, as yet unidentified, stages of differentiation processes.