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Michael H. Gelb - One of the best experts on this subject based on the ideXlab platform.
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Expression of Phospholipases A 2 and C in human corneal epithelial cells. Invest Ophthalmol Vis Sci
2020Co-Authors: Solange Landreville, Michael H. Gelb, Stéphanie Coulombe, Patrick Carrier, Sylvain L Guérin, Christian SalesseAbstract:PURPOSE. To achieve a better understanding of the involvement of Phospholipases in the inflammation and wound-healing processes in human corneal epithelial cells (HCECs), expression of Phospholipase A 2 s (PLA 2 s) and Phospholipase Cs (PLCs) was examined in the human corneal epithelium. METHODS. Specific primers were designed for RT-PCR amplification of the known secreted (s)PLA 2 , cytosolic (c)PLA 2 , and PLC mRNAs. Corresponding PCR products were cloned and the DNA sequenced. Immunofluorescence of flatmounted corneal sections and Western blot analyses were used to detect the PLA 2 s and PLCs expressed by HCECs. RESULTS. The mRNAs for the following Phospholipases were detected by RT-PCR in the HCECs: sPLA 2 GIII, -GX, and -GXIIA; cPLA 2 ␣ and -␥
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intracellular actions of group iia secreted Phospholipase a2 and group iva cytosolic Phospholipase a2 contribute to arachidonic acid release and prostaglandin production in rat gastric mucosal cells and transfected human embryonic kidney cells
Journal of Biological Chemistry, 2006Co-Authors: Zhanglin Ni, Brian P. Smart, Nicole M. Okeley, Michael H. GelbAbstract:Abstract Gastric epithelial cells liberate prostaglandin E2 in response to cytokines as part of the process of healing of gastric lesions. Treatment of the rat gastric epithelial cell line RGM1 with transforming growth factor-α and interleukin-1β leads to synergistic release of arachidonate and production of prostaglandin E2. Results with highly specific and potent Phospholipase A2 inhibitors and with small interfering RNA show that cytosolic Phospholipase A2-α and group IIA secreted Phospholipase A2 contribute to arachidonate release from cytokine-stimulated RGM1 cells. In the late phase of arachidonate release, group IIA secreted Phospholipase A2 is induced (detected at the mRNA and protein levels), and the action of cytosolic Phospholipase A2-α is required for this induction. Results with RGM1 cells and group IIA secreted Phospholipase A2-transfected HEK293 cells show that the group IIA Phospholipase acts prior to externalization from the cells. RGM1 cells also express group XIIA secreted Phospholipase A2, but this enzyme is not regulated by cytokines nor does it contribute to arachidonate release. The other eight secreted Phospholipases A2 were not detected in RGM1 cells at the mRNA level. These results clearly show that cytosolic and group IIA secreted Phospholipases A2 work together to liberate arachidonate from RGM1 cell phospholipids in response to cytokines.
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intracellular actions of group iia secreted Phospholipase a2 and group iva cytosolic Phospholipase a2 contribute to arachidonic acid release and prostaglandin production in rat gastric mucosal cells and transfected human embryonic kidney cells
Journal of Biological Chemistry, 2006Co-Authors: Zhanglin Ni, Brian P. Smart, Nicole M. Okeley, Michael H. GelbAbstract:Gastric epithelial cells liberate prostaglandin E(2) in response to cytokines as part of the process of healing of gastric lesions. Treatment of the rat gastric epithelial cell line RGM1 with transforming growth factor-alpha and interleukin-1beta leads to synergistic release of arachidonate and production of prostaglandin E(2). Results with highly specific and potent Phospholipase A(2) inhibitors and with small interfering RNA show that cytosolic Phospholipase A(2)-alpha and group IIA secreted Phospholipase A(2) contribute to arachidonate release from cytokine-stimulated RGM1 cells. In the late phase of arachidonate release, group IIA secreted Phospholipase A(2) is induced (detected at the mRNA and protein levels), and the action of cytosolic Phospholipase A(2)-alpha is required for this induction. Results with RGM1 cells and group IIA secreted Phospholipase A(2)-transfected HEK293 cells show that the group IIA Phospholipase acts prior to externalization from the cells. RGM1 cells also express group XIIA secreted Phospholipase A(2), but this enzyme is not regulated by cytokines nor does it contribute to arachidonate release. The other eight secreted Phospholipases A(2) were not detected in RGM1 cells at the mRNA level. These results clearly show that cytosolic and group IIA secreted Phospholipases A(2) work together to liberate arachidonate from RGM1 cell phospholipids in response to cytokines.
Zhanglin Ni - One of the best experts on this subject based on the ideXlab platform.
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intracellular actions of group iia secreted Phospholipase a2 and group iva cytosolic Phospholipase a2 contribute to arachidonic acid release and prostaglandin production in rat gastric mucosal cells and transfected human embryonic kidney cells
Journal of Biological Chemistry, 2006Co-Authors: Zhanglin Ni, Brian P. Smart, Nicole M. Okeley, Michael H. GelbAbstract:Abstract Gastric epithelial cells liberate prostaglandin E2 in response to cytokines as part of the process of healing of gastric lesions. Treatment of the rat gastric epithelial cell line RGM1 with transforming growth factor-α and interleukin-1β leads to synergistic release of arachidonate and production of prostaglandin E2. Results with highly specific and potent Phospholipase A2 inhibitors and with small interfering RNA show that cytosolic Phospholipase A2-α and group IIA secreted Phospholipase A2 contribute to arachidonate release from cytokine-stimulated RGM1 cells. In the late phase of arachidonate release, group IIA secreted Phospholipase A2 is induced (detected at the mRNA and protein levels), and the action of cytosolic Phospholipase A2-α is required for this induction. Results with RGM1 cells and group IIA secreted Phospholipase A2-transfected HEK293 cells show that the group IIA Phospholipase acts prior to externalization from the cells. RGM1 cells also express group XIIA secreted Phospholipase A2, but this enzyme is not regulated by cytokines nor does it contribute to arachidonate release. The other eight secreted Phospholipases A2 were not detected in RGM1 cells at the mRNA level. These results clearly show that cytosolic and group IIA secreted Phospholipases A2 work together to liberate arachidonate from RGM1 cell phospholipids in response to cytokines.
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intracellular actions of group iia secreted Phospholipase a2 and group iva cytosolic Phospholipase a2 contribute to arachidonic acid release and prostaglandin production in rat gastric mucosal cells and transfected human embryonic kidney cells
Journal of Biological Chemistry, 2006Co-Authors: Zhanglin Ni, Brian P. Smart, Nicole M. Okeley, Michael H. GelbAbstract:Gastric epithelial cells liberate prostaglandin E(2) in response to cytokines as part of the process of healing of gastric lesions. Treatment of the rat gastric epithelial cell line RGM1 with transforming growth factor-alpha and interleukin-1beta leads to synergistic release of arachidonate and production of prostaglandin E(2). Results with highly specific and potent Phospholipase A(2) inhibitors and with small interfering RNA show that cytosolic Phospholipase A(2)-alpha and group IIA secreted Phospholipase A(2) contribute to arachidonate release from cytokine-stimulated RGM1 cells. In the late phase of arachidonate release, group IIA secreted Phospholipase A(2) is induced (detected at the mRNA and protein levels), and the action of cytosolic Phospholipase A(2)-alpha is required for this induction. Results with RGM1 cells and group IIA secreted Phospholipase A(2)-transfected HEK293 cells show that the group IIA Phospholipase acts prior to externalization from the cells. RGM1 cells also express group XIIA secreted Phospholipase A(2), but this enzyme is not regulated by cytokines nor does it contribute to arachidonate release. The other eight secreted Phospholipases A(2) were not detected in RGM1 cells at the mRNA level. These results clearly show that cytosolic and group IIA secreted Phospholipases A(2) work together to liberate arachidonate from RGM1 cell phospholipids in response to cytokines.
Nicole M. Okeley - One of the best experts on this subject based on the ideXlab platform.
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intracellular actions of group iia secreted Phospholipase a2 and group iva cytosolic Phospholipase a2 contribute to arachidonic acid release and prostaglandin production in rat gastric mucosal cells and transfected human embryonic kidney cells
Journal of Biological Chemistry, 2006Co-Authors: Zhanglin Ni, Brian P. Smart, Nicole M. Okeley, Michael H. GelbAbstract:Abstract Gastric epithelial cells liberate prostaglandin E2 in response to cytokines as part of the process of healing of gastric lesions. Treatment of the rat gastric epithelial cell line RGM1 with transforming growth factor-α and interleukin-1β leads to synergistic release of arachidonate and production of prostaglandin E2. Results with highly specific and potent Phospholipase A2 inhibitors and with small interfering RNA show that cytosolic Phospholipase A2-α and group IIA secreted Phospholipase A2 contribute to arachidonate release from cytokine-stimulated RGM1 cells. In the late phase of arachidonate release, group IIA secreted Phospholipase A2 is induced (detected at the mRNA and protein levels), and the action of cytosolic Phospholipase A2-α is required for this induction. Results with RGM1 cells and group IIA secreted Phospholipase A2-transfected HEK293 cells show that the group IIA Phospholipase acts prior to externalization from the cells. RGM1 cells also express group XIIA secreted Phospholipase A2, but this enzyme is not regulated by cytokines nor does it contribute to arachidonate release. The other eight secreted Phospholipases A2 were not detected in RGM1 cells at the mRNA level. These results clearly show that cytosolic and group IIA secreted Phospholipases A2 work together to liberate arachidonate from RGM1 cell phospholipids in response to cytokines.
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intracellular actions of group iia secreted Phospholipase a2 and group iva cytosolic Phospholipase a2 contribute to arachidonic acid release and prostaglandin production in rat gastric mucosal cells and transfected human embryonic kidney cells
Journal of Biological Chemistry, 2006Co-Authors: Zhanglin Ni, Brian P. Smart, Nicole M. Okeley, Michael H. GelbAbstract:Gastric epithelial cells liberate prostaglandin E(2) in response to cytokines as part of the process of healing of gastric lesions. Treatment of the rat gastric epithelial cell line RGM1 with transforming growth factor-alpha and interleukin-1beta leads to synergistic release of arachidonate and production of prostaglandin E(2). Results with highly specific and potent Phospholipase A(2) inhibitors and with small interfering RNA show that cytosolic Phospholipase A(2)-alpha and group IIA secreted Phospholipase A(2) contribute to arachidonate release from cytokine-stimulated RGM1 cells. In the late phase of arachidonate release, group IIA secreted Phospholipase A(2) is induced (detected at the mRNA and protein levels), and the action of cytosolic Phospholipase A(2)-alpha is required for this induction. Results with RGM1 cells and group IIA secreted Phospholipase A(2)-transfected HEK293 cells show that the group IIA Phospholipase acts prior to externalization from the cells. RGM1 cells also express group XIIA secreted Phospholipase A(2), but this enzyme is not regulated by cytokines nor does it contribute to arachidonate release. The other eight secreted Phospholipases A(2) were not detected in RGM1 cells at the mRNA level. These results clearly show that cytosolic and group IIA secreted Phospholipases A(2) work together to liberate arachidonate from RGM1 cell phospholipids in response to cytokines.
Brian P. Smart - One of the best experts on this subject based on the ideXlab platform.
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intracellular actions of group iia secreted Phospholipase a2 and group iva cytosolic Phospholipase a2 contribute to arachidonic acid release and prostaglandin production in rat gastric mucosal cells and transfected human embryonic kidney cells
Journal of Biological Chemistry, 2006Co-Authors: Zhanglin Ni, Brian P. Smart, Nicole M. Okeley, Michael H. GelbAbstract:Abstract Gastric epithelial cells liberate prostaglandin E2 in response to cytokines as part of the process of healing of gastric lesions. Treatment of the rat gastric epithelial cell line RGM1 with transforming growth factor-α and interleukin-1β leads to synergistic release of arachidonate and production of prostaglandin E2. Results with highly specific and potent Phospholipase A2 inhibitors and with small interfering RNA show that cytosolic Phospholipase A2-α and group IIA secreted Phospholipase A2 contribute to arachidonate release from cytokine-stimulated RGM1 cells. In the late phase of arachidonate release, group IIA secreted Phospholipase A2 is induced (detected at the mRNA and protein levels), and the action of cytosolic Phospholipase A2-α is required for this induction. Results with RGM1 cells and group IIA secreted Phospholipase A2-transfected HEK293 cells show that the group IIA Phospholipase acts prior to externalization from the cells. RGM1 cells also express group XIIA secreted Phospholipase A2, but this enzyme is not regulated by cytokines nor does it contribute to arachidonate release. The other eight secreted Phospholipases A2 were not detected in RGM1 cells at the mRNA level. These results clearly show that cytosolic and group IIA secreted Phospholipases A2 work together to liberate arachidonate from RGM1 cell phospholipids in response to cytokines.
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intracellular actions of group iia secreted Phospholipase a2 and group iva cytosolic Phospholipase a2 contribute to arachidonic acid release and prostaglandin production in rat gastric mucosal cells and transfected human embryonic kidney cells
Journal of Biological Chemistry, 2006Co-Authors: Zhanglin Ni, Brian P. Smart, Nicole M. Okeley, Michael H. GelbAbstract:Gastric epithelial cells liberate prostaglandin E(2) in response to cytokines as part of the process of healing of gastric lesions. Treatment of the rat gastric epithelial cell line RGM1 with transforming growth factor-alpha and interleukin-1beta leads to synergistic release of arachidonate and production of prostaglandin E(2). Results with highly specific and potent Phospholipase A(2) inhibitors and with small interfering RNA show that cytosolic Phospholipase A(2)-alpha and group IIA secreted Phospholipase A(2) contribute to arachidonate release from cytokine-stimulated RGM1 cells. In the late phase of arachidonate release, group IIA secreted Phospholipase A(2) is induced (detected at the mRNA and protein levels), and the action of cytosolic Phospholipase A(2)-alpha is required for this induction. Results with RGM1 cells and group IIA secreted Phospholipase A(2)-transfected HEK293 cells show that the group IIA Phospholipase acts prior to externalization from the cells. RGM1 cells also express group XIIA secreted Phospholipase A(2), but this enzyme is not regulated by cytokines nor does it contribute to arachidonate release. The other eight secreted Phospholipases A(2) were not detected in RGM1 cells at the mRNA level. These results clearly show that cytosolic and group IIA secreted Phospholipases A(2) work together to liberate arachidonate from RGM1 cell phospholipids in response to cytokines.
Edward A Dennis - One of the best experts on this subject based on the ideXlab platform.
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membrane allostery and unique hydrophobic sites promote enzyme substrate specificity
Journal of the American Chemical Society, 2018Co-Authors: Varnavas D Mouchlis, Yuan Chen, Andrew J Mccammon, Edward A DennisAbstract:We demonstrate that lipidomics coupled with molecular dynamics reveal unique Phospholipase A2 specificity toward membrane phospholipid substrates. We discovered unexpected headgroup and acyl-chain specificity for three major human Phospholipases A2. The differences between each enzyme's specificity, coupled with molecular dynamics-based structural and binding studies, revealed unique binding sites and interfacial surface binding moieties for each enzyme that explain the observed specificity at a hitherto inaccessible structural level. Surprisingly, we discovered that a unique hydrophobic binding site for the cleaved fatty acid dominates each enzyme's specificity rather than its catalytic residues and polar headgroup binding site. Molecular dynamics simulations revealed the optimal phospholipid binding mode leading to a detailed understanding of the preference of cytosolic Phospholipase A2 for cleavage of proinflammatory arachidonic acid, calcium-independent Phospholipase A2, which is involved in membrane remodeling for cleavage of linoleic acid and for antibacterial secreted Phospholipase A2 favoring linoleic acid, saturated fatty acids, and phosphatidylglycerol.
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membrane allostery and unique hydrophobic sites promote enzyme substrate specificity
Journal of the American Chemical Society, 2018Co-Authors: Varnavas D Mouchlis, Yuan Chen, Andrew J Mccammon, Edward A DennisAbstract:We demonstrate that lipidomics coupled with molecular dynamics reveal unique Phospholipase A2 specificity toward membrane phospholipid substrates. We discovered unexpected headgroup and acyl-chain specificity for three major human Phospholipases A2. The differences between each enzyme’s specificity, coupled with molecular dynamics-based structural and binding studies, revealed unique binding sites and interfacial surface binding moieties for each enzyme that explain the observed specificity at a hitherto inaccessible structural level. Surprisingly, we discovered that a unique hydrophobic binding site for the cleaved fatty acid dominates each enzyme’s specificity rather than its catalytic residues and polar headgroup binding site. Molecular dynamics simulations revealed the optimal phospholipid binding mode leading to a detailed understanding of the preference of cytosolic Phospholipase A2 for cleavage of proinflammatory arachidonic acid, calcium-independent Phospholipase A2, which is involved in membrane ...
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structure activity relationships of natural and non natural amino acid based amide and 2 oxoamide inhibitors of human Phospholipase a2 enzymes
Bioorganic & Medicinal Chemistry, 2008Co-Authors: Georgia Antonopoulou, Edward A Dennis, Efrosini Barbayianni, Victoria Magrioti, Naomi Cotton, Daren Stephens, Violetta Constantinoukokotou, George KokotosAbstract:A variety of 2-oxoamides and related amides based on natural and non-natural amino acids were synthesized. Their activity on two human intracellular Phospholipases (GIVA cPLA(2) and GVIA iPLA(2)) and one human secretory Phospholipase (GV sPLA(2)) was evaluated. We show that an amide based on (R)-gamma-norleucine is a highly selective inhibitor of GV sPLA(2).
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regulation and inhibition of Phospholipase a2
Annual Review of Pharmacology and Toxicology, 1999Co-Authors: Jesus Balsinde, Maria A Balboa, Paul A Insel, Edward A DennisAbstract:In recent years, there has been great interest in the study of phospholipid metabolism in intact cell systems. Such an interest arises mainly from the discovery that cellular membrane phospholipids serve not only in structural roles, but are also reservoirs of preformed second messenger molecules with key roles in cellular signaling. These second messenger molecules are generated by agonist-induced activation and secretion of intracellular and extracellular Phospholipases, respectively, i.e. enzymes that cleave ester bonds within phospholipids. Prominent members of the large collection of signal-activated Phospholipases are the Phospholipase A2s. These enzymes hydrolyze the sn-2 ester bond of phospholipids, releasing a free fatty acid and a lysophospholipid, both of which may alter cell function. In addition to its role in cellular signaling, Phospholipase A2 has recently been recognized to be involved in a wide number of pathophysiological situations, ranging from systemic and acute inflammatory conditions to cancer. A growing number of pharmacologic inhibitors will help define the role of particular Phospholipase A2s in signaling cascades.
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role of Phospholipase in generating lipid second messengers in signal transduction
The FASEB Journal, 1991Co-Authors: Edward A Dennis, Sue Goo Rhee, Motasim M Billah, Yusuf A. HannunAbstract:Many lipids or lipid-derived products generated by Phospholipases acting on phospholipids in membranes are implicated as mediators and second messengers in signal transduction. Our current understanding of the primary sequence relationships within the class of extracellular Phospholipase A2's and among the numerous forms of the mammalian phosphatidylinositol-specific Phospholipase C's is reviewed. New results suggesting roles for these Phospholipases as well as other Phospholipases such as Phospholipase C and D acting on phosphatidlycholine in generating arachidonic acid for eicosanoid biosynthesis, inositol phosphates for Ca2+ mobilization, and diglyceride for protein kinase C activation through receptor-mediated processes, are discussed. In addition, the possible role of Phospholipases acting on sphingolipids such as sphinglomyelinase in generating lipid mediators is considered.
