Inhibition of the synthesis of glycosphingolipids affects the translocation of proteolipid protein to the myelin membrane.
Brain slices obtained from young rats were incubated with different radioactive precursors, in the presence and absence of L-cycloserine (an inhibitor of the synthesis of sphingosine) in order to explore the possibility that transport of proteolipids--and specifically of the major myelin proteolipid PLP--to the myelin membrane could be coupled to the transport of cerebrosides or sulfatides. At a concentration of 0.15 mM L-cycloserine, the incorporation of [3H] glycine into total proteins, proteolipid apoproteins (APL), PLP, and myelin basic proteins (MBP) of the total homogenate was unaffected by the presence of the inhibitor, whereas the incorporation of [3H] serine into glycosphingolipids decreased markedly. Under similar incubation conditions, the entry of labeled APL and of PLP into the myelin membranes in the presence of L-cycloserine decreased markedly (50%) in comparison to controls. Entry of MBP was not affected by the inhibitor. These results indicate that when synthesis of glycosphingolipids is inhibited by L-cycloserine, thus decreasing the availability of cerebrosides and sulfatides, the translocation of PLP to myelin is disrupted, suggesting that its transport through the oligodendroglial cell could be coupled to the transport of glycosphingolipids and, most probably, of sulfatides.
Pasquini
J M
JM
Departamento de Quimica Biologica-IQUIFIB, CONICET Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires, Argentina.
Guarna
M M
MM
Besio-Moreno
M A
MA
Iturregui
M T
MT
Oteiza
P I
PI
Soto
E F
EF
D000818:Animals; D001370:Axonal Transport / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003523:Cycloserine / Q000494:pharmacology*; D005260:Female; D006028:Glycosphingolipids / Q000378:metabolism*; D008297:Male; D009185:Myelin Proteins / Q000378:metabolism*; D018991:Myelin Proteolipid Protein; D009186:Myelin Sheath / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D006028:Glycosphingolipids; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D003523:Cycloserine