Phospholipase A2 activities in skin physiology and pathology

Dan, Phyllis; Rosenblat, Gennady; Yedgar, Saul

doi:10.1016/j.ejphar.2012.07.023

Cited by 20 publications

(19 citation statements)

References 85 publications

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“…PLA2 and COX-2 in the AA metabolic pathway have been demonstrated to be important in the development and progression of various types of cancer (7,9,28,29). Tumor tissues surgically obtained from patients with HCC have been previously observed to exhibit significantly higher enzymatic activities, and protein and mRNA levels of PLA2, compared with those in surrounding liver tissues or control liver The experiments were performed three times and produced similar results.…”

Section: Discussionmentioning

confidence: 84%

“…The arachidonic acid (AA) metabolic pathway has been recognized to be correlated with the occurrence and development of various types of cancer. Phospholipase A2 (PLA2) and cyclooxygenase (COX) are rate-limiting enzymes in the AA metabolic pathway, which are important in the development and progression of a number of types of cancer (5,6). PLA2 includes three subfamilies: Cytosolic (c)PLA2, secreted PLA2 and calcium-independent PLA2.…”

Section: Introductionmentioning

confidence: 99%

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Berberine induces apoptosis by suppressing the arachidonic acid metabolic pathway in hepatocellular carcinoma

Kan

et al. 2015

Molecular Medicine Reports

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Berberine (BBR) has been suggested as a potential candidate anticancer agent due to its high anticancer activity and multiple mechanisms. In the present study, the inhibitory effect of BBR on hepatocellular carcinoma (HCC) via the suppression of the arachidonic acid (AA) metabolic pathway was investigated. BBR was demonstrated to reduce the viabilities of H22, HepG2 and Bel‑7404 cells, in a dose‑ and time‑dependent manner, and increase the number of apoptotic cells. BBR induced the translocation of apoptosis‑inducing factor between the mitochondria and the nucleus, and had no effects on the protein expression levels of caspase‑3 or ‑9. In addition, BBR significantly suppressed the protein expression levels of cytosolic phospholipase A2 (cPLA2) and cyclooxygenase (COX)‑2 and elevated the content ratio of AA to prostaglandin E2 (PGE2). Furthermore, BBR reduced the volume and weight of tumors in a H22 transplanted tumor model in mice. The results of the present study demonstrated that elevation in the ratio of AA to PGE2 via suppression of the protein expression of cPLA2 and COX‑2 in the AA metabolic pathway is involved in the inhibitory effect of BBR in HCC.

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Section: Discussionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Berberine induces apoptosis by suppressing the arachidonic acid metabolic pathway in hepatocellular carcinoma

Kan

et al. 2015

Molecular Medicine Reports

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“… 28 Besides iPLA 2 , which we studied, a major contribution of cPLA 2 enzyme activity is also to mediate AA release. 29 Downregulation of COX-2 expression leads to increased abundance of its principal metabolic product, PGE 2 , the pleiotropic effects of which appear to affect most, if not all, of the hallmarks of cancer. 5 , 30 PGE 2 is a potent promoter of cell proliferation, motility, invasion, and angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Chemotherapy induces ovarian cancer cell repopulation through the caspase 3-mediated arachidonic acid metabolic pathway

Cui

Zhao

Pan

et al. 2017

OTT

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Recurrence is one of the major causes of high mortality in ovarian cancer. However, the mechanism of ovarian cancer recurrence after chemotherapy has not been fully understood. In the present study, we investigated the effect of chemotherapy-induced tumor microenvironment on the proliferation of SKOV3 cells. We have shown that SKOV3 cells repopulated faster in the culture medium from apoptotic SKOV3 ovarian cancer cells after 24 h of etoposide phosphate (VP-16) treatment. We found that during apoptosis, cleaved caspase 3 could activate cytosolic calcium-independent phospholipase A2, which stimulated the release of arachidonic acid (AA) and triggered the production of prostaglandin E2 (PGE2). An increased level of phosphorylated focal adhesion kinase (FAK) subsequently facilitated the reproliferation of SKOV3 cells, and VP-16-induced repopulation effects were partially reversed by the FAK inhibitor PF562271. Furthermore, the plasma AA-to-PGE2 ratio and tumoral FAK expression of ovarian cancer patients after chemotherapy were significantly lower than those before chemotherapy. Taken together, our results indicate that chemotherapy-induced apoptotic cancer cells can produce PGE2-enriched microenvironment through caspase 3-mediated AA metabolic pathway, which could lead to the abnormal activation of FAK and eventually accelerate the repopulation of SKOV3 cells. Our study provides novel insight into a mechanism that may be utilized to prevent ovarian cancer recurrence in response to chemotherapy.

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“…These enzymes hydrolyze ester bonds at the sn -2 position of glycerophospholipids to release free fatty acids and lysophospholipids, which often trigger signal transduction pathways in animal or human cells. For example, arachidonic acid is the precursor of eicosanoids, prostaglandins, and leukotrienes, all of which play important roles in the inflammatory response [1]–[3]. Specifically, PAF-AH is involved in human health and disease by promoting proinflammation [4], [5] and mediating stress responses in eukaryotic cells.…”

Section: Introductionmentioning

confidence: 99%

Biological Role of Trichoderma harzianum-Derived Platelet-Activating Factor Acetylhydrolase (PAF-AH) on Stress Response and Antagonism

Fan

et al. 2014

PLoS ONE

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We investigated the properties of platelet-activating factor acetylhydrolase (PAF-AH) derived from Trichoderma harzianum. The enzyme, comprised of 572 amino acids, shares high homology with PAF-AH proteins from T. koningii and other microbial species. The optimum enzymatic activity of PAF-AH occurred at pH 6 in the absence of Ca2+ and it localized in the cytoplasm, and we observed the upregulation of PAF-AH expression in response to carbon starvation and strong heat shock. Furthermore, PAF-AH knockout transformant growth occurred more slowly than wild type cells and over-expression strains grown in SM medium at 37°C and 42°C. In addition, PAF-AH expression significantly increased under a series of maize root induction assay. Eicosanoic acid and ergosterol levels decreased in the PAF-AH knockouts compared to wild type cells, as revealed by GC/MS analysis. We also determined stress responses mediated by PAF-AH were related to proteins HEX1, Cu/Zn superoxide dismutase, and cytochrome c. Finally, PAF-AH exhibited antagonistic activity against Rhizoctonia solani in plate confrontation assays. Our results indicate PAF-AH may play an important role in T. harzianum stress response and antagonism under diverse environmental conditions.

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Phospholipase A2 activities in skin physiology and pathology

Cited by 20 publications

References 85 publications

Berberine induces apoptosis by suppressing the arachidonic acid metabolic pathway in hepatocellular carcinoma

Berberine induces apoptosis by suppressing the arachidonic acid metabolic pathway in hepatocellular carcinoma

Chemotherapy induces ovarian cancer cell repopulation through the caspase 3-mediated arachidonic acid metabolic pathway

Biological Role of Trichoderma harzianum-Derived Platelet-Activating Factor Acetylhydrolase (PAF-AH) on Stress Response and Antagonism

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