Suppression by gangliosides of polymerization of glial cytoskeletons prepared from rat astrocytes: a role of sialic acid moiety.
This study investigated in vitro the effects of gangliosides on polymerization of either the depolymerized microfilament preparation (MF) or depolymerized glia filament preparation (GF) extracted separately from the crude cytoskeletal fraction of rat astrocytes. Gangliosides GM1, GM2 and GM3 markedly suppressed polymerization of both MF and GF. The concentration of GM1, GM2 or GM3 required to induce 50% inhibition of the polymerization of 7.5 micrograms MF protein/200 microliters (IC50 of GM1, GM2, or GM3) was 3.2, 2.8 or 5.6 micrograms/200 microliters, respectively. The IC50 of each ganglioside for the polymerization of 7.5 micrograms/200 microliters of GF, furthermore, was 3.3, 3.5 or 7.4 micrograms/200 microliters, respectively, suggesting that the inhibitory activities of GM1 and GM2 on polymerization of both MF and GF were greater than those of GM3. GM1, GM2 and GM3 also suppressed dose-dependently the polymerization of both actin and vimentin. The inhibitory activities of GM1 and GM2 on the polymerization of actin or vimentin were greater than GM3, as in the case of polymerization of MF or GF. The IC50S of GD1a and GT1b for MF polymerization at the same concentration were 2.2 and 1.2 micrograms/200 microliters, respectively, and those for GF polymerization were 2.7 and 1.7 micrograms/200 microliters, respectively. The IC50 of GD3 for MF polymerization was 3.9 micrograms/200 microliters, and that for GF polymerization 4.0 micrograms/200 microliters, implying that the inhibitory activities of GD3 on polymerization of both MF and GF were greater than those of GM3. The findings suggested that the inhibitory activities of gangliosides on MF or GF polymerization became greater with increasing number of sialic acid residues. AsialoGM1 suppressed neither MF nor GF polymerization, and inhibited dose-dependently the ability of GM1 to suppress MF polymerization.
Ito
J I
JI
Department of Biochemistry, Nagoya City University Medical School Mizuho-ku, Japan.
Young
Z L
ZL
Masuda-Isobe
M
M
Tanaka
R
R
D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D005732:Gangliosides / Q000494:pharmacology*; D019158:N-Acetylneuraminic Acid / Q000502:physiology*; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D011108:Polymers / Q000378:metabolism*; D051381:Rats / Q000196:embryology; D017208:Rats, Wistar
D005732:Gangliosides; D011108:Polymers; D019158:N-Acetylneuraminic Acid