Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mannostatin A is a metabolite produced by the microorganism Streptoverticillium verticillus and reported to be a potent competitive inhibitor of rat epididymal alpha-mannosidase. When tested against a number of other arylglycosidases, mannostatin A was inactive toward alpha- and beta-glucosidase and galactosidase as well as beta-mannosidase, but it was a potent inhibitor of jack bean, mung bean, and rat liver lysosomal alpha-mannosidases, with estimated IC50's of 70 nM, 450 nM, and 160 nM, respectively. The type of inhibition was competitive in nature. This compound also proved to be an effective competitive inhibitor of the glycoprotein-processing enzyme mannosidase II (IC50 of about 10-15 nM with p-nitrophenyl alpha-D-mannopyranoside as substrate, and about 90 nM with [3H]mannose-labeled GlcNAc-Man5GlcNAc as substrate). However, it was virtually inactive toward mannosidase I. The N-acetylated derivative of mannostatin A had no inhibitory activity. In cell culture studies, mannostatin A also proved to be a potent inhibitor of glycoprotein processing. Thus, in influenza virus infected Madin Darby canine kidney (MDCK) cells, mannostatin A blocked the normal formation of complex types of oligosaccharides on the viral glycoproteins and caused the accumulation of hybrid types of oligosaccharides. This observation is in keeping with other data which indicate that the site of action of mannostatin A is mannosidase II. Thus, mannostatin A represents the first nonalkaloidal processing inhibitor and adds to the growing list of chemical structures that can have important biological activity.
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PMID:Mannostatin A, a new glycoprotein-processing inhibitor. 227 38

The possibility that circulating immune complexes (IC) could modify lipoprotein lipase (LPL) activity or release was explored in in vitro systems. IC were precipitated at antibody-Ag equivalence by using specific rabbit antisera and Ag from inactivated rubella virus and hemagglutinins from purified whole virions from three prototype strains of influenza (A/Brazil, A/Bangkok, and B/Singapore) as well as from a combined diphtheria and tetanus toxoid adsorbed with inactivated pertussis. After resolubilization, these IC were exposed to delipidated homogenates of rat epididymal fat pads before assay for LPL activity. LPL activity was stimulated two- to three-fold by the presence of 20 to 40 micrograms IC protein. This effect is not caused by the individual components of the IC because neither the specific Ag nor the individual antisera had any significant effect on LPL activity. With the rubella IC, a greater stimulatory effect was seen with increase in IC protein. With the influenza and diphtheria, pertussis, tetanus (DPT) IC, however, inhibition occurred when IC protein exceeded the amount of protein used for the LPL assay. C did not appear to be involved because IC prepared with heated antisera had similar effects. When intact rat epididymal fat pads were exposed to the rubella, influenza, or DPT IC, LPL activity recovered in the suspension medium was increased in each instance compared with pads exposed to a comparable amount of albumin. These findings may have implications for specific lipid changes that may occur during the immediate post-infectious period following rubella, influenza, or infections with the several bacteria whose Ag were present in the DPT IC used in these studies.
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PMID:Effects of in vitro prepared immune complexes on rat adipose tissue lipoprotein lipase. 278 30

Obesity is a metabolic disease characterized by low-level chronic inflammation. Obese individuals are susceptible to infection by viruses, and vaccination against these pathogens is less effective than in nonobese individuals. Here, we sought to explore the immunological environment in a mouse model of obesity induced by a high-fat diet (HFD). HFD treatment increased the body weight and epididymal fat mass. The proportion of activated B cells, T cells, and macrophages was similar between mice in the HFD group and the regular-fat diet (RFD) group. The Th1 cell subpopulation in the HFD group was increased, whereas the proportion of Treg cells was reduced compared with the RFD group. Moreover, T-cell proliferation and cytokine production did not differ between the groups when cells were stimulated with anti-CD3 and anti-CD28 antibodies in vitro. In macrophages, phagocytic activity was higher in mice fed an HFD than in those fed an RFD, but expression levels of CD86 and MHC class II antigens were similar. When macrophages were cultured in vitro, the proportion of CD86-expressing macrophages was lower in those isolated from mice in the HFD group than in those isolated from the RFD group. Furthermore, lipopolysaccharide-induced interleukin 6 (IL-6) and tumor necrosis factor alpha secretions were significantly reduced in macrophages isolated from the HFD group. In addition, influenza vaccine-induced antibodies in the HFD group diminished more rapidly than in the RFD group. These results suggest that poor functionality of macrophages during obesity might contribute to a reduction in vaccine efficacy.
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PMID:Diet-induced obesity reduces the production of influenza vaccine-induced antibodies via impaired macrophage function. 2764 Apr 40