PLA2G2A Human
Description
Gene and Protein Characteristics
PLA2G2A (phospholipase A2, group IIA) is a protein-coding gene located on chromosome 1p36.13. It encodes a 14 kDa secreted phospholipase A2 (sPLA2) enzyme that hydrolyzes the sn-2 ester bond of glycerophospholipids, releasing free fatty acids (e.g., arachidonic acid) and lysophospholipids . Key features include:
PLA2G2A is evolutionarily conserved, with orthologues in mammals and paralogues such as PLA2G2E .
Antimicrobial Defense
PLA2G2A exhibits potent bactericidal activity, particularly against Gram-positive bacteria, due to its affinity for phosphatidylethanolamine (PE)-rich bacterial membranes . It is highly expressed in mucosal barriers (e.g., intestinal Paneth cells, tear glands) and contributes to innate immunity by degrading bacterial membranes and releasing proinflammatory lipid mediators .
Inflammatory Regulation
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Proinflammatory Role: PLA2G2A amplifies inflammation by hydrolyzing phospholipids in extracellular mitochondria and microparticles, generating eicosanoids (e.g., prostaglandins) and mitochondrial DNA, which activate leukocytes .
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Anti-inflammatory Potential: In some contexts, it clears cellular debris and prevents chronic inflammation .
Lipid Metabolism
The enzyme regulates phospholipid metabolism and participates in fatty acid synthesis, particularly in cancer cells driven by oncogenic K-ras .
Inflammatory Diseases
Elevated PLA2G2A levels correlate with severity in:
Expression and Regulation
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Tissue Distribution: Highly expressed in platelets, neutrophils, mast cells, and gastrointestinal tract .
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Inducers: Proinflammatory cytokines (IL-1β, IFN-γ), bacterial LPS .
Therapeutic Implications
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Anti-Infective Agents: PLA2G2A’s bactericidal properties inspire therapies targeting antibiotic-resistant pathogens .
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Cancer Therapeutics: Inhibition of PLA2G2A (e.g., tanshinone I) reduces lipid peroxidation and impairs cancer cell proliferation in pancreatic ductal adenocarcinoma .
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Inflammatory Disease Modulation: Targeting PLA2G2A-mediated microparticle hydrolysis could mitigate sterile inflammation .
Research Challenges and Future Directions
Product Specs
Product Science Overview
sPLA2-IIA plays a significant role in various physiological and pathological processes:
- Inflammation: sPLA2-IIA is an acute phase reactant, meaning its levels increase significantly during systemic inflammation. It has been implicated in inflammatory diseases such as rheumatoid arthritis and sepsis .
- Atherosclerosis: This enzyme is involved in the development of atherosclerosis by mediating monocyte recruitment and differentiation into antigen-presenting cells, which contribute to plaque formation in arteries .
- Innate and Adaptive Immunity: sPLA2-IIA acts as a mediator connecting innate and adaptive immune responses. It induces the differentiation of mononuclear cells and enhances their adhesive and migratory capabilities .
The gene encoding human sPLA2-IIA is located on chromosome 1p35 . Its expression is upregulated in various inflammatory conditions, making it a potential biomarker for diseases involving systemic inflammation . Additionally, sPLA2-IIA has been studied for its role in bacterial infections and its potential as a therapeutic target for inflammatory diseases .
Research on sPLA2-IIA has expanded our understanding of its functions and mechanisms. Studies using knockout and transgenic mice have provided insights into the enzyme’s role in different pathophysiological conditions . Human recombinant sPLA2-IIA is used in research to study its enzymatic properties and potential therapeutic applications.
