Ribonucleases of human cerebrospinal fluid: detection of altered glycosylation relative to their serum counterparts

Schieven, Gary L.; Blank, A.; Dekker, Charles A.

doi:10.1021/bi00264a007

Cited by 21 publications

(11 citation statements)

References 24 publications

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“…The RNAase activity present in cerebrospinal fluid was resolved into two distinct peaks, a major and a minor, by cellulose phosphate column chromatography ( Figure 2) and showed a similar elution profile to that reported previously [44]. The two peaks, which contained RNAases with the same mobilities as those of HB-l and HB-2 when subjected to SDS/PAGE, were pooled separately for further purification and designated CSF-1…”

Section: Partial Purification and Characterization Of Rnaases From Husupporting

confidence: 60%

Two distinct secretory ribonucleases from human cerebrum: purification, characterization and relationships to other ribonucleases

Yasuda

Nadano

Takeshita

et al. 1993

Biochemical Journal

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Two RNAases from human cerebrum were purified to an electrophoretically homogeneous state and their molecular masses were 22.0 kDa (tentatively called RNAase HB-1) and 19.0 kDa (RNAase HB-2). Analyses of the amino acid compositions, N-terminal amino acid sequences and catalytic properties of these enzymes provided strong evidence that they were strictly related to the secretory (sec) RNAases, such as the pancreatic enzyme, very similar immunologically to urinary sec RNAase, but clearly distinguishable from urinary non-secretory (nonsec) RNAase. There were several differences between HB-1 and HB-2, namely their immunological reactivities with specific antibodies, heat-stabilities, attached carbohydrate moieties and molecular masses. In particular, HB-2 appeared to be nonglycosylated, in view of its lack of affinity for several conjugated lectins, the absence of hexosamine and no change in electrophoretic mobility before and after peptide:N-glycosidase F digestion, whereas HB-1 and human sec RNAases purified from kidney, pancreas and urine all appeared to be glycosylated, as they moved to the same position as HB-2 when electrophoresed after glycosidase digestion. An antibody against urinary sec RNAase inhibited 75% and 20% of the total activity of the crude cerebral extract against RNA at pH 8.0 and 6.0 respectively, whereas an antibody against urinary nonsec RNAase had no such inhibitory effect. These findings suggest that yet another type(s) of cerebral RNAase, which is unable to cross-react immunologically with sec and nonsec RNAases, may exist. Two RNAases corresponding to HB-1 and HB-2 were identified in fresh cerebrospinal fluid.

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Section: Partial Purification and Characterization Of Rnaases From Husupporting

confidence: 60%

Two distinct secretory ribonucleases from human cerebrum: purification, characterization and relationships to other ribonucleases

Yasuda

Nadano

Takeshita

et al. 1993

Biochemical Journal

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“…The striking structural characteristics of fl-trace and asialo-transferrin oligosaccharides, high amounts of terminal galactose and/or terminal GIcNAc including bisecting GIcNAc and complete proximal fucosylation as well as significant amounts of peripheral fucosylation, have now led us to establish the hypothesis of' braintype' glycosylation of secretory proteins produced by human brain tissue. These structural motifs seem to be common for glycoproteins synthesized by brain tissue of different mammalian species since they have also been reported for rat [21] and mouse [22] brain membrane glycoproteins as well as human myelin-associated glycoprotein and P0 [23] and ribonucleases from human CSF [24]. In the case of secreted glycoproteins in human serum such structural features would lead to rapid clearance from the circulation due to the carbohydrate specificity of the hepatic receptor system [2] whereas in the central nervous system such a clearance mechanism is apparently not operating.…”

Section: Discussionmentioning

confidence: 56%

‘Brain‐type’ N‐glycosylation of asialo‐transferrin from human cerebrospinal fluid

Hoffmann¹,

Nimtz

Getzlaff

et al. 1995

FEBS Letters

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Asialo-transferrin from human cerebrospinal fluid was purified to homogeneity. Investigation of the structural characteristics of its oligosaccharides support our hypothesis of 'brain-type' glycosylation of intrathecally synthesized cerebrospinal fluid proteins. For carbohydrate structural analysis, high-pH anion-exchange chromatography, methylation analysis, liquid secondary ion-and matrix-assisted laser desorptionl ionization mass spectrometry of the permethylated derivatives were used. The major structure turned out to be a complex-type agalactodiantennary oligosaccharide with bisecting N-acetylglucosamine and proximal fucose. Analysis of a second transferrin preparation containing both asialo-and sialo-transferrin revealed another major glycan species derived from the sialylated transferrin variant which is galactosylated and lacks bisecting N-acetylglucosamine and fucose.

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“…Ribonucleases are very abundant in biological fluids, including CSF. For instance, the half-life (t1/2) of the degradation of RNA in human blood is typically only a few minutes (45,46). However, chemical modifications at the 2' position in the ribose sugar is known to enhance nuclease stability (47)(48)(49).…”

Section: Enzymatic Transcription For Preparing 2'-fluoro Modified Fb9mentioning

confidence: 99%

“…We reasoned that if these aptamers are used in vivo as potential CNS drug candidates, they would have to be exposed at least to CSF. Both CSF and serum contain ribonucleases (45). Thus, characterizing the half-life of FB9s-b and FB9s-r in both fluids would reveal their putative stability and the suitability of using these aptamers in vivo.…”

Section: In Vitro Stability Of Fb9s-b and Fb9s-r In Cerebrospinal Flumentioning

confidence: 99%

A kainate receptor–selective RNA aptamer

Jaremko

Huang

Karl

et al. 2020

Journal of Biological Chemistry

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Kainate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are two major, closely related receptor subtypes in the glutamate ion channel family. Excessive activities of these receptors have been implicated in a number of central nervous system diseases. Designing potent and selective antagonists of these receptors, especially of kainate receptors, is useful for developing potential treatment strategies for these neurological diseases. Here, we report on two RNA aptamers designed to individually inhibit kainate and AMPA receptors. To improve the biostability of these aptamers, we also chemically modified these aptamers by substituting their 2′-OH group with 2′-fluorine. These 2′-fluoro aptamers, FB9s-b and FB9s-r, were markedly resistant to RNase-catalyzed degradation, with a half-life of ∼5 days in rat cerebrospinal fluid or serum-containing medium. Furthermore, FB9s-r blocked AMPA receptor activity. Aptamer FB9s-b selectively inhibited GluK1 and GluK2 kainate receptor subunits, and also GluK1/GluK5 and GluK2/GluK5 heteromeric kainate receptors with equal potency. This inhibitory profile makes FB9s-b a powerful template for developing tool molecules and drug candidates for treatment of neurological diseases involving excessive activities of the GluK1 and GluK2 subunits.

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Ribonucleases of human cerebrospinal fluid: detection of altered glycosylation relative to their serum counterparts

Cited by 21 publications

References 24 publications

Two distinct secretory ribonucleases from human cerebrum: purification, characterization and relationships to other ribonucleases

Two distinct secretory ribonucleases from human cerebrum: purification, characterization and relationships to other ribonucleases

‘Brain‐type’ N‐glycosylation of asialo‐transferrin from human cerebrospinal fluid

A kainate receptor–selective RNA aptamer

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