{"doi":"10.1016/j.ijdevneu.2004.07.002","title":"Role of Ca<sup>2+</sup>‐independent phospholipase A<sub>2</sub> and <i>n</i>−3 polyunsaturated fatty acid docosahexaenoic acid in prostanoid production in brain: perspectives for protection in neuroinflammation","abstract":"<jats:title>Abstract</jats:title><jats:sec><jats:label/><jats:p>Various diseases of the central nervous system are characterized by induction of inflammatory events, which involve formation of prostaglandins. Production of prostaglandins is regulated by activity of phospholipases A<jats:sub>2</jats:sub> and cyclooxygenases. These enzymes release the prostaglandin precursor, the <jats:italic>n</jats:italic>−6 polyunsaturated fatty acid, arachidonic acid and oxidize it into prostaglandin H<jats:sub>2</jats:sub>. Docosahexaenoic acid, which belongs to the <jats:italic>n</jats:italic>−3 class of polyunsaturated fatty acids, was shown to reduce production of prostaglandins after in vivo and in vitro administration. Nevertheless, the fact that in brain tissue cellular phospholipids naturally have a uniquely high content of docosahexaenoic acid was ignored so far in studies of prostaglandin formation in brain tissue. We consider the following possibilities: docosahexaenoic acid might attenuate production of prostaglandins by direct inhibition of cyclooxygenases. Such inhibition was found with the isolated enzyme. Another possibility, which has been already shown is reduction of expression of inducible cyclooxygenase‐2. Additionally, we propose that docosahexaenoic acid could influence intracellular Ca<jats:sup>2+</jats:sup> signaling, which results in changes of activity of Ca<jats:sup>2+</jats:sup>‐dependent phospholipase A<jats:sub>2</jats:sub>, hence reducing the amount of arachidonic acid available for prostaglandin production. Astrocytes, the main type of glial cells in the brain control the release of arachidonic acid, docosahexaenoic acid and the formation of prostaglandins. Our recently obtained data revealed that the release of arachidonic and docosahexaenoic acids in astrocytes is controlled by different isoforms of phospholipase A<jats:sub>2</jats:sub>, i.e. Ca<jats:sup>2+</jats:sup>‐dependent phospholipase A<jats:sub>2</jats:sub> and Ca<jats:sup>2+</jats:sup>‐independent phospholipase A<jats:sub>2</jats:sub>, respectively. Moreover, the release of arachidonic and docosahexaenoic acids is differently regulated through Ca<jats:sup>2+</jats:sup>‐ and cAMP‐dependent signal transduction pathways. Based on analysis of the current literature and our own data we put forward the hypothesis that Ca<jats:sup>2+</jats:sup>‐independent phospholipase A<jats:sub>2</jats:sub> and docosahexaenoic acid are promising targets for treatment of inflammatory related disorders in brain. We suggest that Ca<jats:sup>2+</jats:sup>‐independent phospholipase A<jats:sub>2</jats:sub> and docosahexaenoic acid might be crucially involved in brain‐specific regulation of prostaglandins.</jats:p></jats:sec>","journal":"International Journal of Developmental Neuroscience","year":2004,"id":37874,"datarank":2.858984774068661,"base_score":4.204692619390966,"endowment":4.204692619390966,"self_citation_contribution":0.6307038929086449,"citation_network_contribution":2.2282808811600163,"self_endowment_contribution":0.6307038929086449,"citer_contribution":2.2282808811600163,"corpus_percentile":null,"corpus_rank":null,"citation_count":66,"citer_count":55,"citers_with_citation_signal":55,"citers_with_endowment":55,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":188898,"name":"Marina Sergeeva","orcid":null,"position":1,"is_corresponding":false},{"id":188899,"name":"Georg Reiser","orcid":null,"position":2,"is_corresponding":false},{"id":188897,"name":"Mikhail Strokin","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.204692619390966,"endowment":4.204692619390966,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"15465285","pmcid":null,"openalex_id":"https://openalex.org/W2039138323","authors":[],"funders":[{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"unidentified","title":"unidentified"},{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"","title":null}],"total_grants":2,"fwci":4.6055,"citation_percentile":0.94223898,"influential_citations":1,"citation_trend":[{"year":2012,"count":4},{"year":2013,"count":1},{"year":2014,"count":3},{"year":2016,"count":2},{"year":2017,"count":2},{"year":2018,"count":6},{"year":2019,"count":4},{"year":2020,"count":3},{"year":2021,"count":4},{"year":2022,"count":1},{"year":2023,"count":1}],"oa_status":"bronze","license":"Wiley Online Library User Agreement","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1016/j.ijdevneu.2004.07.002","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1016/j.ijdevneu.2004.07.002","host_type":"BRONZE"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1016/j.ijdevneu.2004.07.002","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0736574804000875?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0736574804000875?httpAccept=text/plain","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1016%2Fj.ijdevneu.2004.07.002","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1016/j.ijdevneu.2004.07.002","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.1016/j.ijdevneu.2004.07.002","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.ijdevneu.2004.07.002","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/15465285","host_type":"repository"},{"url":"https://dx.doi.org/10.1016/j.ijdevneu.2004.07.002","host_type":""}],"fields_of_study":["Inflammatory mediators and NSAID effects","Peroxisome Proliferator-Activated Receptors","Fatty Acid Research and Health","Medicine","Biology","Chemistry","0301 basic medicine","0303 health sciences","03 medical and health sciences","Animals","Calcium","Calcium Signaling","Docosahexaenoic Acids","Encephalitis","Fatty Acids, Omega-3","Fatty Acids, Unsaturated","Homeostasis","Humans","Multienzyme Complexes","Phospholipases A","Phospholipases A2","Prostaglandins","Signal Transduction","Triglycerides"],"mesh_terms":["Animals","Calcium","Docosahexaenoic Acids","Encephalitis","Fatty Acids, Unsaturated","Homeostasis","Humans","Multienzyme Complexes","Phospholipases A","Prostaglandins","Triglycerides","Signal Transduction","Fatty Acids, Omega-3","Calcium Signaling","Phospholipases A2"],"keywords":["Docosahexaenoic acid","Arachidonic acid","Phospholipase A2","Polyunsaturated fatty acid","Biochemistry","Phospholipase","Prostaglandin","Biology","Eicosapentaenoic acid","Fatty acid","Cyclooxygenase","Eicosanoid","Chemistry","Enzyme","Docosahexaenoic Acids","Phospholipases A","Phospholipases A2","Multienzyme Complexes","Fatty Acids, Omega-3","Fatty Acids, Unsaturated","Prostaglandins","Animals","Encephalitis","Homeostasis","Humans","Calcium","Calcium Signaling","Triglycerides","Signal Transduction"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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