- 作者: Robert K. Yu; Toshio Ariga; Hiide Yoshino; Ritsuko Katoh-Semba; Shunlin Ren
- 作者服務機構: a Department of Biochemistry and Molecular; Biophysics, Medical College of Virginia, Virginia Commonwealth University, Richmond, Va., USA, and; b Institute of Developmental Research, Aichi Prefecture Colony, Aichi, Japan
- 中文摘要: --
- 英文摘要: Previous studies have shown that certain glycosphingolipids may function as modulators of protein kinase C (PKC) activity. To study the structure-activity relationship, we examined the effects of 17 gangliosides, 10 neutral glycolip- ids, as well as sulfatide, psychosine and ceramide on PKC activity in PC 12D cells. Using an in vitro assay system, we found that all but one (GQ 1 b) ganglio- side inhibited PKC activity at concentrations between 25 and 100μM and the potency was proportional to the number of sialic acid residues. However, at lower concentrations several gangliosides, including GM 1 and LM 1 be- haved as mild activators of PKC activity. GQ 1 b had no effect within the range 0.1-10 μM, but acted as a mild activator of PKC activity at 25 μM. On the other hand, fucosyl-GM 1 and GM 1 containing blood group B determinant, which are abundant in PC 12 cells, were potent inhibitors of PKC activity. Among the neutral glycosphingolipids tested, LacCer, Gb3, Ga1Gb3, and GA1, all of which have a terminal galactose residue, were found to be ineffec- tive or acted as mild activators of PKC activity. In contrast, GA2, Gb4 and Gb5 which have a terminal N-acetylgalactosamine residue, were potent inhib- itors of the PKC activity. Thus, the terminal sugar residue may play a pivotal role in determining the effect of glycosphingolipids in modulating PKC activi- ty. In addition, we also found that Ga1Cer containing normal fatty acids acted as potent activators of PKC activity. Ceramide and G1cCer appeared to be ineffective in modulating PKC activity, whereas psychosine and sulfatides appeared to be inhibitory. We conclude that the carbohydrate head groups and the hydrophobic groups of gangliosides and neutral glycolipids may modulate the PKC system in unique manners, which may in turn affect various biologi- cal processes in the cell.
- 中文關鍵字: --
- 英文關鍵字: Protein kinase C; Gangliosides; Neutral glycosphingolipids; PC12D; Pheochromocytoma cells