Abnormal N-acetylglucosaminyltransferase expression in prefrontal cortex in schizophrenia
Autor: | Toni M. Mueller, James H. Meador-Woodruff, Vahram Haroutunian, Jordyn M. Kippe |
---|---|
Rok vydání: | 2015 |
Předmět: |
Male
Glycan Glycosylation Blotting Western Prefrontal Cortex N-Acetylglucosaminyltransferases Article Abnormal glycosylation Rats Sprague-Dawley symbols.namesake chemistry.chemical_compound N-linked glycosylation medicine Animals Humans Gray Matter Prefrontal cortex Biological Psychiatry Aged biology Endoplasmic reticulum Golgi apparatus Cell biology Dorsolateral prefrontal cortex carbohydrates (lipids) Psychiatry and Mental health medicine.anatomical_structure chemistry Immunology symbols biology.protein Schizophrenia Haloperidol Female Antipsychotic Agents |
Zdroj: | Schizophrenia research. 166(1-3) |
ISSN: | 1573-2509 |
Popis: | Changes in the extent of the post-translational modification glycosylation have been previously reported in several brain regions in schizophrenia. Quality control within the endoplasmic reticulum and Golgi, branching of glycans, intracellular trafficking and targeting, protein-protein interactions, and endocytosis are processes regulated by both N-linked and O-linked glycosylation. Previous studies in schizophrenia have found altered glycan biosynthesis and abnormal glycan levels in cerebrospinal fluid (CSF) and plasma, as well as altered expression in frontal cortex of glycosyltransferase transcripts encoding proteins associated with both N- and O-linked glycosylation. The N-acetylglucosaminyltransferases (GlcNAcTs) are glycosylating enzymes that play a key role in adding N-acetylglucosamine (GlcNAc) to substrates to facilitate their proper trafficking, intracellular targeting, and cellular function. Given previous results indicating abnormal glycosylation in schizophrenia, we hypothesized that these GlcNAcTs may be abnormally expressed in this illness. We measured protein expression of nine distinct GlcNAcTs by Western blot analysis in postmortem samples of dorsolateral prefrontal cortex (DLPFC) from twelve pairs of elderly patients with schizophrenia and comparison subjects. We found decreased protein expression of UDP-GlcNAc:BetaGal Beta-1,3 GlcNAcT 8 (B3GNT8) and mannosyl (alpha-1,3-)-glycoprotein beta-1,4 GlcNAcT (MGAT4A) expression in schizophrenia. These data provide further evidence that glycosylation is dysregulated in schizophrenia, and suggest a potential mechanism associated with alterations in protein function, trafficking, and intracellular targeting in this illness. |
Databáze: | OpenAIRE |
Externí odkaz: |