Phospholipase A2, a nonnegligible enzyme superfamily in gastrointestinal diseases

Wu, Wei; Xu, Xinru; Huang, Chunhong

doi:10.1016/j.biochi.2021.12.014

Cited by 10 publications

(3 citation statements)

References 142 publications

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“…From the metabolic pathways of EICs, ECBs and SPMs shown in Figure 1 , Figure 2 and Figure 3 , it is apparent that these families of bioactive lipids share key enzymes, such as the lipase responsible for the release from phospholipid precursors (PLA 2 ) and three oxygenases able to generate from AA: (i) epoxyeicosatrienoic acids (CYP450); (ii) 12-hydroxyeicosatetraenoic acids (12-LOX); and (iii) cyclic prostanoid(-like) oxidative derivatives (COX-2). Of note, PLA 2 belongs to a superfamily of enzymes that play major roles in several pathophysiological processes, e.g., mast cell biology [ 45 ], atherosclerotic cardiovascular disease [ 46 ], and gastrointestinal diseases [ 47 ]. Unsurprisingly, PLA 2 enzymes are able to mobilize unique bioactive lipids in multiple ways that are spatiotemporally regulated, thus triggering distinct signaling pathways.…”

Section: Interactions In Lipid Signaling Pathwaysmentioning

confidence: 99%

Deciphering Complex Interactions in Bioactive Lipid Signaling

Maccarrone

2023

Molecules

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Lipids are usually viewed as metabolic fuel and structural membrane components. Yet, in recent years, different families of lipids able to act as authentic messengers between cells and/or intracellularly have been discovered. Such lipid signals have been shown to exert their biological activity via specific receptors that, by triggering distinct signal transduction pathways, regulate manifold pathophysiological processes in our body. Here, endogenous bioactive lipids produced from arachidonic acid (AA) and other poly-unsaturated fatty acids will be presented, in order to put into better perspective the relevance of their mutual interactions for health and disease conditions. To this end, metabolism and signal transduction pathways of classical eicosanoids, endocannabinoids and specialized pro-resolving mediators will be described, and the intersections and commonalities of their metabolic enzymes and binding receptors will be discussed. Moreover, the interactions of AA-derived signals with other bioactive lipids such as shingosine-1-phosphate and steroid hormones will be addressed.

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Section: Interactions In Lipid Signaling Pathwaysmentioning

confidence: 99%

Deciphering Complex Interactions in Bioactive Lipid Signaling

Maccarrone

2023

Molecules

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“…These include the secretory PLA 2 enzymes, which hydrolyze extracellular phospholipids to lysophospholipids, as well as intracellular enzymes such as the cytosolic PLA 2 and the calcium-independent PLA 2 , which hydrolyze phospholipids in different intracellular compartments [8]. The products of PLA 2 reactions, lysophospholipids, and nonesterified fatty acids, are bioactive lipid metabolites that serve as intracellular and extracellular signals in regulating cell functions and pathophysiological process such as obesity/diabetes, cardiovascular disease, cancer, neurodegenerative disorders, and inflammatory bowel disease [9]. These lipid metabolites may also serve as substrates for the synthesis of other active lipid metabolites such as prostaglandins, thromboxane, leukotrienes, and epoxyeicosatrienoic acids that modulate cardiometabolic and inflammatory disease pathogenesis [10].…”

Section: Introductionmentioning

confidence: 99%

Inactivation of Group 1B Phospholipase A2 Enhances Disease Recovery and Reduces Experimental Colitis in Mice

Haller,

Wolfkiel,

Jaeschke

et al. 2023

IJMS

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Phospholipase A2 (PLA2) enzymes influence inflammatory bowel disease in both positive and negative manners depending on the type of PLA2 that is expressed. This study explored the influence of the abundantly expressed Group 1B PLA2 (PLA2G1B) on ulcerative colitis. Wild-type C57BL/6J mice and Pla2g1b−/− mice were treated with dextran sulfate sodium (DSS) for 5 days to induce epithelial injury, followed by another 5 days without DSS for recovery. The Pla2g1b−/− mice displayed significantly less body weight loss, colitis pathology, and disease activity indexes compared to the wild-type mice. The differences in colitis were not due to differences in the colonic lysophospholipid levels, but higher numbers of stem and progenitor cells were found in the intestines of Pla2g1b−/− mice compared to the wild-type mice. The DSS-treated Pla2g1b−/− mice also showed higher expressions of genes that are responsible for epithelial repair and lower expressions of proinflammatory cytokine genes in the colon, as well as reduced inflammatory cytokine levels in the plasma. In vitro experiments revealed the PLA2G1B stimulation of inflammatory cytokine expression by myeloid cells. PLA2G1B inactivation protects against DSS-induced colitis in mice by increasing the intestinal stem cell reservoir for epithelial repair and reducing myeloid cell inflammation in the diseased colon. Thus, PLA2G1B may be a target for colitis management.

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“…Phospholipase A2 (PLA2; EC 3.1.1.4), from the esterase superfamily, is closely related to lipid metabolism [9]. Secretory phospholipase A2 (sPLA2) is the most abundant subgroup of PLA2, and it is characterized by highly conserved Ca 2+ -binding sites, His-Asp catalytic dyads, and rich disulfide bonds.…”

Section: Introductionmentioning

confidence: 99%

Trichosporon asahii PLA2 Gene Enhances Drug Resistance to Azoles by Improving Drug Efflux and Biofilm Formation

Luan

Liu

et al. 2023

IJMS

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Trichosporon asahii is an opportunistic pathogen that can cause severe or even fatal infections in patients with low immune function. sPLA2 plays different roles in different fungi and is also related to fungal drug resistance. However, the mechanism underlying its drug resistance to azoles has not yet been reported in T. asahii. Therefore, we investigated the drug resistance of T. asahii PLA2 (TaPLA2) by constructing overexpressing mutant strains (TaPLA2OE). TaPLA2OE was generated by homologous recombination of the recombinant vector pEGFP-N1-TaPLA2, induced by the CMV promoter, with Agrobacterium tumefaciens. The structure of the protein was found to be typical of sPLA2, and it belongs to the phospholipase A2_3 superfamily. TaPLA2OE enhanced antifungal drug resistance by upregulating the expression of effector genes and increasing the number of arthrospores to promote biofilm formation. TaPLA2OE was highly sensitive to sodium dodecyl sulfate and Congo red, indicating impaired cell wall integrity due to downregulation of chitin synthesis or degradation genes, which can indirectly affect fungal resistance. In conclusion, TaPLA2 overexpression enhanced the resistance to azoles of T. asahii by enhancing drug efflux and biofilm formation and upregulating HOG-MAPK pathway genes; therefore, it has promising research prospects.

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Phospholipase A2, a nonnegligible enzyme superfamily in gastrointestinal diseases

Cited by 10 publications

References 142 publications

Deciphering Complex Interactions in Bioactive Lipid Signaling

Deciphering Complex Interactions in Bioactive Lipid Signaling

Inactivation of Group 1B Phospholipase A2 Enhances Disease Recovery and Reduces Experimental Colitis in Mice

Trichosporon asahii PLA2 Gene Enhances Drug Resistance to Azoles by Improving Drug Efflux and Biofilm Formation

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