Phospholipase A2 Biochemistry

Burke, John E.; Dennis, Edward A.

doi:10.1007/s10557-008-6132-9

Cited by 359 publications

(294 citation statements)

References 140 publications

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“…cPLA 2 ␣ can be activated by several mechanisms (reviewed in Refs. 11,12). It contains a Ca 2ϩ binding domain (C2) that allows interaction with membrane phospholipids in response to increased intracellular Ca 2ϩ concentrations, and the single substitution D43N in this domain abrogates the Ca 2ϩ -dependent translocation of cPLA 2 ␣ to membranes (13)(14)(15).…”

Section: Intracellular Lipid Droplets (Ld)mentioning

confidence: 99%

“…In this regard, anionic phospholipids like phosphatidylinositol 4,5-bisphosphate (PtdIns-4,5-P 2 ) (20, 21) and ceramide 1-phosphate (Cer-1-P) (22)(23)(24)(25) bind specific regions of the enzyme and decrease its Ca 2ϩ requirement to interact with membranes. Also, phosphorylation of cPLA 2 ␣ at Ser residues 505, 515, and 727 appears to play a role in enzyme activation (11,12). Among these sites, it is generally accepted that Ser-505 is the one that leads to increased catalytic activity (26), and phosphorylation of Ser-505 depends on MAPK, among which most reports implicate ERK and p38 (11,12).…”

Section: Intracellular Lipid Droplets (Ld)mentioning

confidence: 99%

“…Also, phosphorylation of cPLA 2 ␣ at Ser residues 505, 515, and 727 appears to play a role in enzyme activation (11,12). Among these sites, it is generally accepted that Ser-505 is the one that leads to increased catalytic activity (26), and phosphorylation of Ser-505 depends on MAPK, among which most reports implicate ERK and p38 (11,12).…”

Section: Intracellular Lipid Droplets (Ld)mentioning

confidence: 99%

“…JNK, but Not ERK or p38 MAPK, Is Responsible for cPLA 2 ␣ Phosphorylation and LD Biogenesis-cPLA 2 ␣ is phosphorylated at Ser-505 by MAPKs (11,12), and to dissect the pathway during LD biogenesis, we monitored JNK, p38, and ERK MAPKs at different times after FBS replacement. As shown in Fig.…”

Section: Formation Of [ 3 H]cer-1-p-[mentioning

confidence: 99%

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JNK and Ceramide Kinase Govern the Biogenesis of Lipid Droplets through Activation of Group IVA Phospholipase A2

Gubern

Barceló-Torns

Barneda

et al. 2009

Journal of Biological Chemistry

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The biogenesis of lipid droplets (LD) induced by serum depends on group IVA phospholipase A 2 (cPLA 2 ␣). This work dissects the pathway leading to cPLA 2 ␣ activation and LD biogenesis. Both processes were Ca 2؉ -independent, as they took place after pharmacological blockade of Ca 2؉ transients elicited by serum or chelation with 1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid tetrakis(acetoxymethyl ester). The single mutation D43N in cPLA 2 ␣, which abrogates its Ca 2؉ binding capacity and translocation to membranes, did not affect enzyme activation and formation of LD. In contrast, the mutation S505A did not affect membrane relocation of the enzyme in response to Ca 2؉ but prevented its phosphorylation, activation, and the appearance of LD. Expression of specific activators of different mitogen-activated protein kinases showed that phosphorylation of cPLA 2 ␣ at Ser-505 is due to JNK. This was confirmed by pharmacological inhibition and expression of a dominant-negative form of the upstream activator MEKK1. LD biogenesis was accompanied by increased synthesis of ceramide 1-phosphate. Overexpression of its synthesizing enzyme ceramide kinase increased phosphorylation of cPLA 2 ␣ at Ser-505 and formation of LD, and its down-regulation blocked the phosphorylation of cPLA 2 ␣ and LD biogenesis. These results demonstrate that LD biogenesis induced by serum is regulated by JNK and ceramide kinase.

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Section: Intracellular Lipid Droplets (Ld)mentioning

confidence: 99%

Section: Intracellular Lipid Droplets (Ld)mentioning

confidence: 99%

Section: Intracellular Lipid Droplets (Ld)mentioning

confidence: 99%

Section: Formation Of [ 3 H]cer-1-p-[mentioning

confidence: 99%

See 2 more Smart Citations

JNK and Ceramide Kinase Govern the Biogenesis of Lipid Droplets through Activation of Group IVA Phospholipase A2

Gubern

Barceló-Torns

Barneda

et al. 2009

Journal of Biological Chemistry

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“…Phospholipases A2 (PLA2s) constitute a superfamily of enzymes that catalyze the hydrolysis of fatty acids from the sn-2 position of glycerophospholipids to produce free fatty acids and lysophospholipids, which are both involved in signaling transduction and metabolic processes, and account for a vast number of diseases [1,2] . PLA2s, then, are obvious candidates for pharmacological research and intervention.…”

Section: Introductionmentioning

confidence: 99%

The inhibition of lipoprotein-associated phospholipase A2 exerts beneficial effects against atherosclerosis in LDLR-deficient mice

Zhang

Wang

et al. 2011

Acta Pharmacol Sin

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Aim: To investigate the effects of darapladib, a specific inhibitor of lipoprotein-associated phospholipase A2 (lp-PLA2), on inflammation and atherosclerotic formation in the low density lipoprotein receptor (LDLR)-deficient mice. Methods: Six-week-old LDLR-deficient mice were fed an atherogenic high-fat diet for 17 weeks and then randomly divided into two groups. One group was administered darapladib (50 mg·kg -1 ·d -1 ; po) for 6 weeks. The other group was administered saline as a control. Serum lipid levels were measured using the corresponding kits, and three inflammatory markers -interleukin-6 (IL-6), C reactive protein (hs-CRP), and platelet activating factor (PAF) -were determined using ELISA. Atherosclerotic plaque areas were stained with Sudan IV, and inflammatory gene expression at the lesions was evaluated using quantitative real-time PCR. Results: The body weight and serum lipid level between the two groups were similar at the end of the dietary period. The serum lp-PLA2 activity, hs-CRP and IL-6 levels, however, were significantly reduced in the darpladib group. The inhibition of lp-PLA2 did not alter the serum PAF level. Furthermore, the plaque area, from the aortic arch to the abdominal aorta, was significantly reduced in the darpladib group. Additionally, the expression of inflammatory genes monocyte chemotactic protein-1 (MCP-1) and vascular cell adhesion molecule-1 (VCAM-1) was significantly reduced at the lesions in the darapladib group. Conclusion: Inhibition of lp-PLA2 by darapladib decreases the inflammatory burden and atherosclerotic plaque formation in LDLRdeficient mice, which may be a new strategy for the treatment of atherosclerosis.

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Prevalence, predictors, and characteristics of off‐treatment fatigue in breast cancer survivors

Andrykowski

Donovan

Laronga

et al. 2010

Cancer

150

146

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BACKGROUND Lack of consensus regarding how to identify cancer patients with significant fatigue has hampered research regarding cancer-related fatigue (CRF). METHODS Specific criteria were used to identify CRF cases in women with stage 0-II breast cancer (BC group, n = 304). Women completed assessments before adjuvant therapy (baseline), end of adjuvant therapy (Post-Tx), and 6 and 42 months after end of adjuvant therapy (6 and 42 Month Post-Tx). At each, women completed a clinical interview and questionnaires assessing physical and mental health. A healthy control (HC) group with no history of BC (n = 337) completed 2 similar assessments 36 months apart. RESULTS Off-treatment CRF prevalence was 9% and 13% at the 6 and 42 Month Post-Tx assessments, respectively. Thus, 15% of the sample evidenced off-treatment CRF with 7% evidencing delayed onset CRF. CRF at the 6 Month Post-Tx assessment was associated only with CRF at baseline (OR = 3.2) and Post-Tx assessments (OR = 3.9). CRF at the 42 Month Post-Tx assessment was associated with CRF at the Post-Tx assessment (OR = 6.1), obesity at baseline, and several baseline measures of coping in response to fatigue. Off-treatment CRF cases differed markedly from CRF noncases and healthy controls on a spectrum of health status indices (mean effect size >1.0 SD). CONCLUSIONS Results document the prevalence of off-treatment and delayed onset CRF, suggest the utility of a cognitive-behavioral model of CRF, and support NCCN guidelines recommending monitoring fatigue across the cancer trajectory.

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Phospholipase A2 Biochemistry

Cited by 359 publications

References 140 publications

JNK and Ceramide Kinase Govern the Biogenesis of Lipid Droplets through Activation of Group IVA Phospholipase A2

JNK and Ceramide Kinase Govern the Biogenesis of Lipid Droplets through Activation of Group IVA Phospholipase A2

The inhibition of lipoprotein-associated phospholipase A2 exerts beneficial effects against atherosclerosis in LDLR-deficient mice

Prevalence, predictors, and characteristics of off‐treatment fatigue in breast cancer survivors

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