Da. Aquino et al., ANTISENSE OLIGONUCLEOTIDE TO THE 70-KDA HEAT-SHOCK COGNATE PROTEIN INHIBITS SYNTHESIS OF MYELIN BASIC-PROTEIN, Neurochemical research, 21(4), 1996, pp. 417-422
Transfection of rat oligodendrocytes with an oligonucleotide sequence
complementary to the mRNA encoding the initial ten amino acids of the
rat 70-kDa heat shock cognate protein (HSC70) resulted in a rapid (wit
hin 24 h) and significant reduction in HSC70 synthesis (69% of control
cells transfected with sense oligonucleotide). A further decrease to
approximately 44% of controls was detected after 2 days. At that time,
HSC70 protein content fell to approximately 49% of controls, and a si
gnificant reduction in the synthesis of myelin basic protein (MBP) was
first detected (66% of controls). After 5 days, HSC70 synthesis retur
ned to control levels. As HSC70 protein content recovered, so did the
synthesis of MBP. Throughout the 5-day experimental period, only minor
changes were detected in cell morphology, overall pattern of protein
synthesis and the synthesis and content of proteolipid protein (PLP) a
nd the pi isoenzyme of glutathione-S-transferase (pi). These data show
that when HSC70 protein content is sufficiently reduced by antisense
oligonucleotide, synthesis of MBP (but not PLP or pi) is corresponding
ly down-regulated, and provide evidence consistent with the role of HS
C70 as a chaperone for MBP.