Alternative splicing generates a diacylglycerol kinase α transcript that acts as a dominant-negative modulator of superoxide production in localized aggressive periodontitis.
Background: Diacylglycerol (DAG), levels of which are tightly regulated by diacylglycerol kinases (DGKs), is a lipid mediator linked to key biologic functions. Members of the DGK family undergo alternative splicing, generating the protein diversity necessary to control different intracellular DAG po...
| Publicado en: | Journal of Periodontology Vol. 85; no. 7; pp. 934 - 944 |
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| Autores principales: | , , , , |
| Formato: | research Journal Article |
| Publicado: |
Wiley-Blackwell
Jul2014
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=107796329&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 107796329 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00223492 4CH jtl: Journal of Periodontology issn: 00223492 maglogo: N pubinfo: dt: Jul2014 vid: 85 iid: 7 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 107796329 107796329 NLM24171497 2012635879 10.1902/jop.2013.130468 NLM24171497 PMC4527154 107796329 ppf: 934 ppct: 10 formats: tig: atl: Alternative splicing generates a diacylglycerol kinase α transcript that acts as a dominant-negative modulator of superoxide production in localized aggressive periodontitis. aug: au: Batista Jr, Eraldo L Kantarci, Alpdogan I Hasturk, Hatice Van Dyke, Thomas E Batista, Eraldo L Jr affil: Department of Diagnostics and Surgical Sciences and Department of Oral Biology, Faculty of Dentistry, University of Manitoba, Winnipeg, MB, Canada; previously, Department of Periodontology and Oral Biology, Boston University Goldman School of Dental Medicine, Boston, MA sug: subj: Aggressive Periodontitis Blood RNA Transferases Peroxides Metabolism Adult Aggressive Periodontitis Amino Acids Animals Case Control Studies Primates Mutation Molecular Structure Genes Female Human Male Neutrophils Proteins Genetic Techniques Adult: 19-44 years Female Male ab: Background: Diacylglycerol (DAG), levels of which are tightly regulated by diacylglycerol kinases (DGKs), is a lipid mediator linked to key biologic functions. Members of the DGK family undergo alternative splicing, generating the protein diversity necessary to control different intracellular DAG pools. DGKα function is altered in polymorphonuclear neutrophils (PMNs) of patients with localized aggressive periodontitis (LAgP), suggesting a genetic basis. Here, the authors assess DGKα spliced transcripts in human LAgP neutrophils.Methods: In an expression library of a patient with LAgP, PMNs were screened for different DGKα transcripts. Real-time polymerase chain reaction and in vitro expression assays were performed to assess the fate of different transcripts on protein translocation and superoxide production in human leukemia cells (HL-60) and COS-7 cells.Results: A DGKα transcript that lacks exon 10 (DGKαΔ10) and generates a premature stop codon and a truncated protein was identified as being upregulated in LAgP neutrophils. In vitro assays revealed that DGKαΔ10 translocation occurred even in the absence of important regulatory motifs. Transfection of HL-60 neutrophil-like cells with the DGKαΔ10 spliced variant induced an increase in the stimulated production of superoxide anion replicating the phenotype of LAgP PMNs.Conclusion: DGKαΔ10 can act as a dominant-negative transcript that can modulate superoxide production and provides an example of genetic regulation of the inflammatory response that may be relevant to human inflammatory diseases such as LAgP. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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