Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.1.52 (PNGase F)
 1,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Animals sensitized to methamphetamine (METH) have altered dopaminergic systems, including dopamine transporter (DAT) activity. We investigated the effects induced by a sensitizing dose (5 mg/kg, i.p. per day for 5 days) of METH on rat behavior, DA transport by the DAT, DAT density, and inhibition of DA transport by METH in both the nucleus accumbens and striatum. We further investigated possible changes to glycosylation of the DAT after METH sensitization. The dosing paradigm caused an increased stereotyped response in rats treated with METH compared with saline controls. In animals treated with METH, DA transport velocities were increased by 6.4% in the nucleus accumbens and decreased by 21% in the striatum. Western blots demonstrated that DAT density was unchanged in the nucleus accumbens of METH-treated animals, but striatal DAT density was decreased by 20%. Further studies investigating METH inhibition of DA transport found that in the nucleus accumbens of METH-treated animals, the IC(50) was shifted to a larger value (from 0.81 to 1.45 microM). In the striatum, the IC(50) was decreased by 19% (from 1.00 to 0.81 microM) in METH-treated animals. Studies using glycosidase treatments and Western blots revealed that glycosylation was effectively removed by N-glycanase and neuraminidase, but not O-glycosidase or alpha-mannosidase. These studies also suggest that glycosylation was not altered in METH-treated animals. This study demonstrates that in animals sensitized to METH, the DAT is differentially regulated in different areas of the brain important for drug abuse, and that DA transport changes induced by METH are not due to DAT density, but to changes in the kinetics of the DAT. Additionally, this study suggests that glycosylation may not play a role in DAT activity changes after METH exposure.
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PMID:Neuronal dopamine transporter activity, density and methamphetamine inhibition are differentially altered in the nucleus accumbens and striatum with no changes in glycosylation in rats behaviorally sensitized to methamphetamine. 1865 43

Sub-fractions of all apo B-100 containing lipoproteins (low density lipoproteins, very low density lipoproteins and intermediate density lipoproteins) with reduced contents of sialic acid were found in vivo in human blood. These lipoproteins were inclined to spontaneously form aggregates and were able to stimulate accumulation of cholesterol in cells cultured from human aortic intima. In vitro treatment of apo B-containing lipoproteins with 2,6- and 2,3-specific sialidases, alpha-mannosidase, endoglycosidases F1 or F2 or peptide-N-glycanase F also stimulated aggregation and increased the ability of these particles to potentiate cholesterol accumulation in cells of the intact human aortic intima. So, deglycosylation of various apo B-containing lipoproteins possibly occurs in the blood, decreases their resistance to aggregation and increases the ability of these particles to stimulate accumulation of cholesterol in human aortic intima cells, thereby increasing their atherogenic potential.
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PMID:Deglycosylation of apo B-containing lipoproteins increase their ability to aggregate and to promote intracellular cholesterol accumulation in vitro. 1908 34

In eukaryotic cells, N-glycosylation has been recognized as one of the most common and functionally important co- or post-translational modifications of proteins. "Free" forms of N-glycans accumulate in the cytosol of mammalian cells, but the precise mechanism for their formation and degradation remains unknown. Here, we report a method for the isolation of yeast free oligosaccharides (fOSs) using endo-beta-1,6-glucanase digestion. fOSs were undetectable in cells lacking PNG1, coding the cytoplasmic peptide:N-glycanase gene, suggesting that almost all fOSs were formed from misfolded glycoproteins by Png1p. Structural studies revealed that the most abundant fOS was M8B, which is not recognized well by the endoplasmic reticulum-associated degradation (ERAD)-related lectin, Yos9p. In addition, we provide evidence that some of the ERAD substrates reached the Golgi apparatus prior to retrotranslocation to the cytosol. N-Glycan structures on misfolded glycoproteins in cells lacking the cytosol/vacuole alpha-mannosidase, Ams1p, was still quite diverse, indicating that processing of N-glycans on misfolded glycoproteins was more complex than currently envisaged. Under ER stress, an increase in fOSs was observed, whereas levels of M7C, a key glycan structure recognized by Yos9p, were unchanged. Our method can thus provide valuable information on the molecular mechanism of glycoprotein ERAD in Saccharomyces cerevisiae.
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PMID:Free oligosaccharides to monitor glycoprotein endoplasmic reticulum-associated degradation in Saccharomyces cerevisiae. 2015 Apr 26

Endoplasmic reticulum (ER)-associated degradation (ERAD) is a quality control system for newly synthesized proteins in the ER; nonfunctional proteins, which fail to form their correct folding state, are then degraded. The cytoplasmic peptide:N-glycanase is a deglycosylating enzyme that is involved in the ERAD and releases N-glycans from misfolded glycoproteins/glycopeptides. We have previously identified a mutant plant toxin protein, RTA (ricin A-chain nontoxic mutant), as the first in vivo Png1 (the cytoplasmic peptide:N-glycanase in Saccharomyces cerevisiae)-dependent ERAD substrate. Here, we report a new genetic device to assay the Png1-dependent ERAD pathway using the new model protein designated RTL (RTA-transmembrane-Leu2). Our extensive studies using different yeast mutants identified various factors involved in RTL degradation. The degradation of RTA/RTL was independent of functional Sec61 but was dependent on Der1. Interestingly, ER-mannosidase Mns1 was not involved in RTA degradation, but it was dependent on Htm1 (ERAD-related alpha-mannosidase in yeast) and Yos9 (a putative degradation lectin), indicating that mannose trimming by Mns1 is not essential for efficient ERAD of RTA/RTL. The newly established RTL assay will allow us to gain further insight into the mechanisms involved in the Png1-dependent ERAD-L pathway.
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PMID:Identification of an Htm1 (EDEM)-dependent, Mns1-independent Endoplasmic Reticulum-associated Degradation (ERAD) pathway in Saccharomyces cerevisiae: application of a novel assay for glycoprotein ERAD. 2051 Dec 19


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