Avtor/Urednik     Vardjan, Nina
Naslov     Študij molekularnega mehanizma presinaptično nevrotoksičnega delovanja amoditoksinov
Tip     monografija
Kraj izdaje     Ljubljana
Založnik     Medicinska fakulteta
Leto izdaje     2003
Obseg     str. 118
Jezik     slo
Abstrakt     Ammodytoxins (Atx) are presynaptically acting neurotoxic secretory phospholipases AZ (sPLA2) of type IIA from the venom of the long-nosed viper (Vipera ammodytes ammodytes). They block the release of acetylcholine from the axon terminals of motor neurons, causing muscle paralysis. The molecular mechanism underlying the presynaptic neurotoxicity of Atx and the related presynaptically neurotoxic sPLA2 is still unclear. It has been proposed that sPLA2 neurotoxicity is dependent on its enzymatic activity and binding to specific receptors in or on axon terminals of motor neurons. Studying the presynaptically neurotoxic action of Atx two high molecular mass receptors for Atx were identified in porcine tissues, one in porcine liver, L200, and the other in porcine brain, R180. We purified L200 in an active form. Using tandem mass spectrometry, both porcine high-molecular mass receptors were identified as members of the group of M-type sPLA2 receptors (sPLAZRs). Since we found only one gene for M-type sPLA2R in the porcine genome, it is likely that porcine M-type sPLA2Rs, which differ in molecular mass by approx.20 kDa, are modified differently, either post-translationally or post-transcriptionally. Deglycosylation studies on R180 and L200 showed that the majority of the differences in molecular mass . between the receptors are the consequence of different N-glycosylation of the receptors. However, some additional structural differences between the receptors must exist, since porcine M-type sPLAzRs still differ in molecular mass by approx. 5 kDa after N-deglycosylation. This difference could be the consequence of an additional post-translational modification of the receptors (D-glycosylation) or a post-transcriptional modification of their mRNA (alternative splicing). (Abstract truncated at 2000 characters).
Deskriptorji     VIPER VENOMS
PHOSPHOLIPASES A
RECEPTORS, PRESYNAPTIC
BINDING SITES
AXONS
RECOMBINANT PROTEINS
HEPARIN
CARRIER PROTEINS
PLASMIDS
MICE
SWINE
RABBITS
LIVER
CEREBRAL CORTEX
CLONING, MOLECULAR
TRANSFORMATION, GENETIC
DNA FRAGMENTATION
BASE SEQUENCE
AMINO ACID SEQUENCE