Roles of Acidic Phospholipids and Nucleotides in Regulating Membrane Binding and Activity of a Calcium-independent Phospholipase A2 Isoform

Morrison, Kylee; Witte, K. H.; Mayers, Jonathan R.; Schuh, Amber L.; Audhya, Anjon

doi:10.1074/jbc.m112.391508

Cited by 14 publications

(13 citation statements)

References 48 publications

(62 reference statements)

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“…Based on the lipidomic analysis, it is postulated that during embryogenesis, G6PD regulates the activity of PLA 2 s, which are critical for organismal development. 25 , 26 , 27 , 28 , 29 As iPLAs family was considered the main phospholipase in C. elegans , 25 iPLA activity was determined ( Figure 4a ). Compared with mock, iPLA activity was increased in G6PD-deficient adults (2-fold, P <0.05) and even more so in G6PD-deficient embryos (10-fold, P <0.005).…”

Section: Resultsmentioning

confidence: 99%

Impaired embryonic development in glucose-6-phosphate dehydrogenase-deficient Caenorhabditis elegans due to abnormal redox homeostasis induced activation of calcium-independent phospholipase and alteration of glycerophospholipid metabolism

et al. 2017

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Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a commonly pervasive inherited disease in many parts of the world. The complete lack of G6PD activity in a mouse model causes embryonic lethality. The G6PD-deficient Caenorhabditis elegans model also shows embryonic death as indicated by a severe hatching defect. Although increased oxidative stress has been implicated in both cases as the underlying cause, the exact mechanism has not been clearly delineated. In this study with C. elegans, membrane-associated defects, including enhanced permeability, defective polarity and cytokinesis, were found in G6PD-deficient embryos. The membrane-associated abnormalities were accompanied by impaired eggshell structure as evidenced by a transmission electron microscopic study. Such loss of membrane structural integrity was associated with abnormal lipid composition as lipidomic analysis revealed that lysoglycerophospholipids were significantly increased in G6PD-deficient embryos. Abnormal glycerophospholipid metabolism leading to defective embryonic development could be attributed to the increased activity of calcium-independent phospholipase A2 (iPLA) in G6PD-deficient embryos. This notion is further supported by the fact that the suppression of multiple iPLAs by genetic manipulation partially rescued the embryonic defects in G6PD-deficient embryos. In addition, G6PD deficiency induced disruption of redox balance as manifested by diminished NADPH and elevated lipid peroxidation in embryos. Taken together, disrupted lipid metabolism due to abnormal redox homeostasis is a major factor contributing to abnormal embryonic development in G6PD-deficient C. elegans.

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Section: Resultsmentioning

confidence: 99%

Impaired embryonic development in glucose-6-phosphate dehydrogenase-deficient Caenorhabditis elegans due to abnormal redox homeostasis induced activation of calcium-independent phospholipase and alteration of glycerophospholipid metabolism

et al. 2017

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“…As the major constituents of the biologic membranes, the phospholipids can prevent the stability of cell membrane degeneration and promote recovery via improving cell membrane, protecting cells and mitochondria membrane against injury, promoting synthesis of lipoproteins, and increasing membrane fluidity and enzyme activities (Morrison et al, 2012 ; Zhang et al, 2014 ). Phospholipids also allow selected molecules to diffuse or move across the cell membrane into cells (Bishop and Bell, 1988 ; Zhang et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Berberine Could Ameliorate Cardiac Dysfunction via Interfering Myocardial Lipidomic Profiles in the Rat Model of Diabetic Cardiomyopathy

et al. 2018

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Background: Diabetic cardiomyopathy (DCM) is considered to be a distinct clinical entity independent of concomitant macro- and microvascular disorders, which is initiated partly by disturbances in energy substrates. This study was to observe the dynamic modulations of berberine in DCM rats and explore the changes of lipidomic profiles of myocardial tissue.Methods: Sprague-Dawley (SD) rats were fed high-sucrose and high-fat diet (HSHFD) for totally 22 weeks and intraperitoneally (i.p.) injected with 30 mg/kg of streptozotocin (STZ) at the fifth week to induce DCM. Seventy-two hours after STZ injection, the rats were orally given with berberine at 10, 30 mg/kg and metformin at 200 mg/kg, respectively. Dynamic changes of cardiac function, heart mass ratios and blood lipids were observed at f 4, 10, 16, and 22, respectively. Furthermore, lipid metabolites in myocardial tissue at week 16 were profiled by the ultra-high-performance liquid chromatography coupled to a quadruple time of flight mass spectrometer (UPLC/Q-TOF/MS) approach.Results: Berberine could protect against cardiac diastolic and systolic dysfunctions, as well as cardiac hypertrophy, and the most effective duration is with 16-week of administration. Meanwhile, 17 potential biomarkers of phosphatidylcholines (PCs), phosphatidylethanolamines (PEs) and sphingolipids (SMs) of DCM induced by HSFD/STZ were identified. The perturbations of lipidomic profiles could be partly reversed with berberine intervention, i.e., PC (16:0/20:4), PC (18:2/0:0), PC (18:0/18:2), PC (18:0/22:5), PC (20:4/0:0), PC (20:4/18:0), PC (20:4/18:1), PC (20:4/20:2), PE (18:2/0:0), and SM (d18:0/16:0).Conclusions: These results indicated a close relationship between PCs, PEs and SMs and cardiac damage mechanisms during development of DCM. The therapeutic effects of berberine on DCM are partly caused by interferences with PCs, PEs, and SMs metabolisms.

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“…Our group found that PEDF and the PEDF-derived peptide 44 mer inhibit oxygen-glucose deprivation-induced oxidative stress through PEDFR/iPLA2 [27]. However, Preeti Subramanian and his colleagues reported that pigment PEDF prevents retinal cell death via PEDF-R and PLA2 enzymatic activity, and it is critical for upregulating Bcl-2 and cell survival [28]. We are not clear which activity played a role to inhibit the activation of the NLRP3 inflammasome.…”

Section: Discussionmentioning

confidence: 99%

PEDF Inhibits the Activation of NLRP3 Inflammasome in Hypoxia Cardiomyocytes through PEDF Receptor/Phospholipase A2

Zhang

Wang

Guan

et al. 2016

IJMS

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The nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome has been linked to sterile inflammation, which is involved in ischemic injury in myocardial cells. Pigment epithelium-derived factor (PEDF) is a multifunctional secreted glycoprotein with many biological activities, such as anti-inflammatory, antioxidant and anti-angiogenic properties. However, it is not known whether and how PEDF acts to regulate the activation of the NLRP3 inflammasome in cardiomyocytes. In the present study, we used the neonatal cardiomyocytes models of ischemia-like conditions to evaluate the mitochondrial fission and the activation of the NLRP3 inflammasome. We also determined the mechanism by which PEDF inhibits hypoxia-induced activation of the NLRP3 inflammasome. We found that PEDF decreased the activation of the NLRP3 inflammasome in neonatal cardiomyocytes through pigment epithelial-derived factor receptor/calcium-independent phospholipase A2 (PEDFR/iPLA2). Meanwhile, PEDF reduced Drp1-induced mitochondrial fission and mitochondrial fission-induced mitochondrial DNA (mtDNA), as well as mitochondrial reactive oxygen species (mtROS) release into cytosol through PEDFR/iPLA2. We also found that PEDF inhibited mitochondrial fission-induced NLRP3 inflammasome activation. Furthermore, previous research has found that endogenous cytosolic mtDNA and mtROS can serve as activators of NLRP3 inflammasome activity. Therefore, we hypothesized that PEDF can protect against hypoxia-induced activation of the NLRP3 inflammasome by inhibiting mitochondrial fission though PEDFR/iPLA2.

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Roles of Acidic Phospholipids and Nucleotides in Regulating Membrane Binding and Activity of a Calcium-independent Phospholipase A2 Isoform

Cited by 14 publications

References 48 publications

Impaired embryonic development in glucose-6-phosphate dehydrogenase-deficient Caenorhabditis elegans due to abnormal redox homeostasis induced activation of calcium-independent phospholipase and alteration of glycerophospholipid metabolism

Impaired embryonic development in glucose-6-phosphate dehydrogenase-deficient Caenorhabditis elegans due to abnormal redox homeostasis induced activation of calcium-independent phospholipase and alteration of glycerophospholipid metabolism

Berberine Could Ameliorate Cardiac Dysfunction via Interfering Myocardial Lipidomic Profiles in the Rat Model of Diabetic Cardiomyopathy

PEDF Inhibits the Activation of NLRP3 Inflammasome in Hypoxia Cardiomyocytes through PEDF Receptor/Phospholipase A2

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