ENHANCED DEGRADATION OF MESSENGER-RNA ENCODING MYELIN PROTEINS BY TERMINAL COMPLEMENT COMPLEXES IN OLIGODENDROCYTES

Sublytic terminal C complexes (TCC) are capable of stimulating cells a nd affect the target cell activity. Activation of TCC that generates l eukotriene B4 in oligodendrocytes, the myelin-forming cells of the cen tral nervous system, is also a required process in antibody-mediated d emyelination of rodent cerebellar explants. In the present study, the effect of TCC on myelin protein gene expression was studied in primary rat oligodendrocytes in culture. Sublytic activation of serum C reduc ed accumulation of mRNA encoding proteolipid protein (PLP) and myelin basic protein (MBP) within 1 h, but not beta-actin mRNA. C activation, on the other hand, induced sustained expression of c-jun mRNA. Experi ments using C7-deficient human serum to determine the role of TCC show ed that selective MBP and PLP mRNA down-regulation was achieved only w hen C7 was reconstituted to form TCC. The C7 requirement was also obse rved in the presence of alpha-amanitin. Post-transcriptional regulatio n was explored by determining mRNA decay, which demonstrated that the MBP and PLP mRNA were selectively destabilized when C7 was reconstitut ed. Limited exploration of the signals responsible for the TCC effect revealed that down-regulation of mRNA by TCC was significantly influen ced by Ca2+ on PLP, whereas MBP did not show the same Ca2+ sensitivity as PLP. The TCC-mediated MBP mRNA decay was completely abrogated by H A1004, an inhibitor for the cAMP- and cGMP-dependent protein kinases, but not by H7, a protein kinase C inhibitor.