| Cerebrospinal fluid secretory Ca2+-dependent phospholipase A2 activity is increased in Alzheimer disease. | |
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MedLine Citation:
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PMID: 19850632 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: The phospholipase A(2) (PLA2) family comprises multiple isoenzymes that vary in their physicochemical properties, cellular localizations, calcium sensitivities, and substrate specificities. Despite these differences, PLA2s share the ability to catalyze the synthesis of the precursors of the proinflammatory mediators. To investigate the potential of PLA2 as a biomarker in screening neuroinflammatory disorders in both clinical and research settings, we developed a PLA2 assay and determined the predominant types of PLA2 activity in cerebrospinal fluid (CSF). METHODS: We used liposomes composed of a fluorescent probe (bis-Bodipy FL C11-PC [1,2-bis-(4,4- difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-undecanoyl)-sn-glycero-3-phosphocholine]) and 1,2-dioleoyl-l-alpha-phosphatidylcholine as a substrate to measure CSF PLA2 activity in a 96-well microtiter plate format. We established the type of CSF PLA2 activity using type-specific inhibitors of PLA2. RESULTS: Using 5 microL CSF per assay, our PLA2 activity assay was reproducible with CVs <15% in 2 CSF samples and for recombinant secretory Ca(2+)-dependent PLA2 (sPLA2) in concentrations ranging from 0.25 to 1 micromol/L. This PLA2 assay allowed identification of sPLA2 activity in lumbar CSF from healthy individuals 20-77 years old that did not depend on either sex or age. Additionally, CSF sPLA2 activity was found to be increased (P = 0.0008) in patients with Alzheimer disease. CONCLUSIONS: Adult human CSF has sPLA2 activity that can be measured reliably with the assay described. This enzyme activity in the CSF is independent of both sex and age and might serve as a valuable biomarker of neuroinflammation, as we demonstrated in Alzheimer disease. |
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Authors:
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Sonia Chalbot; Henrik Zetterberg; Kaj Blennow; Tormod Fladby; Inge Grundke-Iqbal; Khalid Iqbal |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-10-22 |
Journal Detail:
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Title: Clinical chemistry Volume: 55 ISSN: 1530-8561 ISO Abbreviation: Clin. Chem. Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-11-30 Completed Date: 2009-12-28 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 9421549 Medline TA: Clin Chem Country: United States |
Other Details:
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Languages: eng Pagination: 2171-9 Citation Subset: IM |
Affiliation:
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New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314-6399, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Alzheimer Disease / cerebrospinal fluid, enzymology* Biological Markers / cerebrospinal fluid Calcium / physiology* Fluorescent Dyes Humans Middle Aged Phosphatidylcholines Phospholipases A2, Secretory / cerebrospinal fluid* Reference Values Young Adult |
| Grant Support | |
ID/Acronym/Agency:
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AG028538/AG/NIA NIH HHS; R01 AG019158-08/AG/NIA NIH HHS; R01 AG028538-01A1/AG/NIA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/1,2-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diazaindacene-3-dodecanoyl)-sn-glycero-3-phosphocholine; 0/Biological Markers; 0/Fluorescent Dyes; 0/Phosphatidylcholines; 10015-85-7/1,2-oleoylphosphatidylcholine; 7440-70-2/Calcium; EC 3.1.1.4/Phospholipases A2, Secretory |
| Comments/Corrections | |
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