Induction of astroglial growth inhibition and differentiation by sialosyl cholesterol.
Normal rat astroblasts in culture were exposed to 11 sialosyl or cholesterol derivatives at concentrations lower than 20 microM. Synthesized sialosyl cholesterols (alpha- and beta-D-N-acetyl neuraminyl cholesterols) and cholesterol sulfate showed a marked growth inhibitory action. Sialosyl cholesterol uniquely evoked an astroglia-like stellation resembling that induced by glia maturation factor (GMF) as well as a suppression of GMF-induced mitogenesis of astroblasts. The minimal incubation period of sialosyl cholesterol for the initiation of growth inhibition was as short as one hour. The inhibitory effect retained an irreversibility even after removal of the drug. Cytosolic protein with 58 kDa Mr in size was specifically phosphorylated by sialosyl cholesterol through a certain protein kinase dependent on neither Ca2+ nor cyclic AMP. The competition experiment of sialosyl cholesterol action revealed that sialosyl and cholesterol moieties were indispensable for the phenomena. These results most likely imply that sialosyl cholesterol alters the membrane microenvironment to affect the affinity of growth factor receptor, protein kinase activity, and/or cytoskeletal anchorages.
Ito
J
J
Department of Biochemistry, Nagoya City University Medical School, Japan.
Kato
T
T
Okumura-Noji
K
K
Miyatani
Y
Y
Tanaka
R
R
Tsuji
S
S
Nagai
Y
Y
D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002788:Cholesterol Esters / Q000494:pharmacology; D005732:Gangliosides / Q000494:pharmacology; D020904:Glia Maturation Factor; D008970:Molecular Weight; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D012794:Sialic Acids / Q000494:pharmacology*; D013936:Thymidine
D002788:Cholesterol Esters; D005732:Gangliosides; D020904:Glia Maturation Factor; D009419:Nerve Tissue Proteins; D012794:Sialic Acids; D002784:Cholesterol; C007045:cholesteryl sulfate; D013936:Thymidine