The Experts below are selected from a list of 51504 Experts worldwide ranked by ideXlab platform
Richard W Gross - One of the best experts on this subject based on the ideXlab platform.
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depletion of intracellular calcium stores activates smooth muscle cell calcium independent phospholipase a2 a novel mechanism underlying Arachidonic Acid mobilization
Journal of Biological Chemistry, 1997Co-Authors: Matthew J Wolf, John Turk, Jian Wang, Richard W GrossAbstract:Herein we present multiple lines of evidence which demonstrate that depletion of internal calcium stores is both necessary and sufficient for the activation of calcium-independent phospholipase A2 during arginine vasopressin (AVP)-mediated mobilization of Arachidonic Acid in A-10 smooth muscle cells. First, AVP-induced [3H]Arachidonic Acid release was independent of increases in cytosolic calcium yet was decreased by pharmacological inhibition of the release of calcium ion from internal stores. Second, thapsigargin induced the dramatic release of [3H]Arachidonic Acid from A-10 cells at a similar rate as the AVP-induced release of Arachidonic Acid, and the release of Arachidonic Acid by either AVP or thapsigargin was entirely inhibited by (E)-6-(bromomethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one (BEL). Third, the magnitude of thapsigargin-induced [3H]Arachidonic Acid release was entirely independent of alterations in cytosolic calcium concentration. Fourth, A23187 resulted in the BEL-inhibitable release of [3H]Arachidonic Acid from A-10 cells even when ionophore-induced increases in cytosolic calcium were completely prevented by calcium chelators. Fifth, pretreatment of A-10 cells with a calmodulin antagonist (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, HCl) resulted in the time-dependent decrease of subsequent thapsigargin-induced [3H]Arachidonic Acid release. Collectively, these results identify a novel paradigm which links alterations in calcium homeostasis to the calmodulin-mediated regulation of calcium-independent phospholipase A2 through the depletion of internal calcium stores.
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Arachidonic Acid release from aortic smooth muscle cells induced by arg8 vasopressin is largely mediated by calcium independent phospholipase a2
Journal of Biological Chemistry, 1993Co-Authors: John J Lehman, John Turk, Kathryn A Brown, Sasanka Ramanadham, Richard W GrossAbstract:To identify the phospholipase mediating the majority of [Arg8]vasopressin (AVP)-induced release of Arachidonic Acid in A-10 smooth muscle cells, we exploited the specificity inherent in the mechanism-based inhibitor, (E)-6-(bromomethylene)tetrahydro-3-(1-naphthalenyl)-2H-pyran-2-one (HELSS), which possesses a 1,000-fold selectivity for inhibition of calcium-independent versus calcium-dependent phospholipases A2. Utilizing [3H]Arachidonic Acid-labeled A-10 smooth muscle cells, one-half of AVP-inducible [3H]Arachidonic Acid release was inhibited by pretreatment with only 1 microM HELSS and two-thirds of AVP-stimulated [3H]Arachidonic Acid release was inhibited by 5 microM HELSS. The inhibition of [3H]Arachidonic Acid release by HELSS was saturable (i.e. no additional inhibition of [3H]Arachidonic Acid release was present at 10 microM HELSS), specific (i.e. the activities of six intracellular enzymes, as well as the rate of glucose oxidation, were not altered by HELSS treatment), and nontoxic (i.e. HELSS-treated cells excluded trypan blue dye and did not leak intracellular enzymes into the medium). Collectively, these results demonstrate that HELSS blocks AVP-induced Arachidonic Acid release by specific and irreversible inhibition of calcium-independent phospholipase A2 and underscore the importance of calcium-independent phospholipase A2 in agonist-induced Arachidonic Acid release in at least some cell types.
Christina S. Leslie - One of the best experts on this subject based on the ideXlab platform.
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regulation of the specific release of Arachidonic Acid by cytosolic phospholipase a2
Prostaglandins Leukotrienes and Essential Fatty Acids, 2004Co-Authors: Christina S. LeslieAbstract:Abstract Cytosolic phospholipase A 2 alpha (cPLA 2 α ) is the only PLA 2 that exhibits specificity for sn-2 Arachidonic Acid consistent with its primary role in mediating the agonist-induced release of Arachidonic Acid for eicosanoid production. It is subject to complex mechanisms of regulation that ensure that levels of free Arachidonic Acid are tightly controlled. The calcium-induced translocation of cPLA 2 α from the cytosol to membrane regulates its interaction with phospholipid substrate. cPLA 2 α is additionally regulated by phosphorylation on sites in the catalytic domain. Because of its central position as the upstream regulatory enzyme for initiating production of several classes of bioactive lipid mediators (leukotrienes, prostaglandins and platelet-activating factor), it is a potentially important pharmacological target for the control of inflammatory diseases.
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Regulation of Arachidonic Acid availability for eicosanoid production.
Biochemistry and cell biology = Biochimie et biologie cellulaire, 2004Co-Authors: Christina S. LeslieAbstract:Mammalian cells have developed specific pathways for the incorporation, remodeling, and release of Arachidonic Acid. Acyltransferase and transacylase pathways function to regulate the levels of esterified Arachidonic Acid in specific phospholipid pools. There are several distinct, differentially regulated phospholipases A2 in cells that mediate agonist-induced release of Arachidonic Acid. These pathways are important in controlling cellular levels of free Arachidonic Acid. Both Arachidonic Acid and its oxygenated metabolites are potent bioactive mediators that regulate a myriad of physiological and pathophysiological processes.
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regulation of Arachidonic Acid release and cytosolic phospholipase a2 activation
Journal of Leukocyte Biology, 1999Co-Authors: Miguel A Gijon, Christina S. LeslieAbstract:The 85-kDa cytosolic PLA2 (cPLA2) mediates agonist-induced Arachidonic Acid release in many cell models, including mouse peritoneal macrophages. cPLA2 is regulated by an increase in intracellular calcium, which binds to an amino- terminal C2 domain and induces its translocation to the nuclear envelope and endoplasmic reticulum. Phosphorylation of cPLA2 on S505 by mitogen- activated protein kinases (MAPK) also contributes to activation. In macrophages, zymosan induces a transient increase in intracellular calcium and acti- vation of MAPK, which together fully activate cPLA2 and synergistically promote Arachidonic Acid release. There are alternative pathways for regulat- ing cPLA2 in macrophages because PMA and oka- daic Acid induce Arachidonic Acid release without increasing calcium. The baculovirus expression system is a useful model to study cPLA2 activation. Sf9 cells expressing cPLA2 release Arachidonic Acid to either A23187 or okadaic Acid. cPLA2 is phos- phorylated on multiple sites in Sf9 cells, and phos- phorylation of S727 is preferentially induced by okadaic Acid. However, the phosphorylation sites are non-essential and only S505 phosphorylation partially contributes to cPLA2 activation in this model. Although okadaic Acid does not increase intracellular calcium in Sf9 cells, calcium binding by the C2 domain is necessary for Arachidonic Acid release. A23187 and okadaic Acid activate cPLA2 by different mechanisms, yet both induce transloca- tion to the nuclear envelope in Sf9 cells. The results demonstrate that alternative regulatory pathways can lead to cPLA2 activation and Arachidonic Acid release. J. Leukoc. Biol. 65: 330-336; 1999.
John Turk - One of the best experts on this subject based on the ideXlab platform.
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depletion of intracellular calcium stores activates smooth muscle cell calcium independent phospholipase a2 a novel mechanism underlying Arachidonic Acid mobilization
Journal of Biological Chemistry, 1997Co-Authors: Matthew J Wolf, John Turk, Jian Wang, Richard W GrossAbstract:Herein we present multiple lines of evidence which demonstrate that depletion of internal calcium stores is both necessary and sufficient for the activation of calcium-independent phospholipase A2 during arginine vasopressin (AVP)-mediated mobilization of Arachidonic Acid in A-10 smooth muscle cells. First, AVP-induced [3H]Arachidonic Acid release was independent of increases in cytosolic calcium yet was decreased by pharmacological inhibition of the release of calcium ion from internal stores. Second, thapsigargin induced the dramatic release of [3H]Arachidonic Acid from A-10 cells at a similar rate as the AVP-induced release of Arachidonic Acid, and the release of Arachidonic Acid by either AVP or thapsigargin was entirely inhibited by (E)-6-(bromomethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one (BEL). Third, the magnitude of thapsigargin-induced [3H]Arachidonic Acid release was entirely independent of alterations in cytosolic calcium concentration. Fourth, A23187 resulted in the BEL-inhibitable release of [3H]Arachidonic Acid from A-10 cells even when ionophore-induced increases in cytosolic calcium were completely prevented by calcium chelators. Fifth, pretreatment of A-10 cells with a calmodulin antagonist (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, HCl) resulted in the time-dependent decrease of subsequent thapsigargin-induced [3H]Arachidonic Acid release. Collectively, these results identify a novel paradigm which links alterations in calcium homeostasis to the calmodulin-mediated regulation of calcium-independent phospholipase A2 through the depletion of internal calcium stores.
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Arachidonic Acid release from aortic smooth muscle cells induced by arg8 vasopressin is largely mediated by calcium independent phospholipase a2
Journal of Biological Chemistry, 1993Co-Authors: John J Lehman, John Turk, Kathryn A Brown, Sasanka Ramanadham, Richard W GrossAbstract:To identify the phospholipase mediating the majority of [Arg8]vasopressin (AVP)-induced release of Arachidonic Acid in A-10 smooth muscle cells, we exploited the specificity inherent in the mechanism-based inhibitor, (E)-6-(bromomethylene)tetrahydro-3-(1-naphthalenyl)-2H-pyran-2-one (HELSS), which possesses a 1,000-fold selectivity for inhibition of calcium-independent versus calcium-dependent phospholipases A2. Utilizing [3H]Arachidonic Acid-labeled A-10 smooth muscle cells, one-half of AVP-inducible [3H]Arachidonic Acid release was inhibited by pretreatment with only 1 microM HELSS and two-thirds of AVP-stimulated [3H]Arachidonic Acid release was inhibited by 5 microM HELSS. The inhibition of [3H]Arachidonic Acid release by HELSS was saturable (i.e. no additional inhibition of [3H]Arachidonic Acid release was present at 10 microM HELSS), specific (i.e. the activities of six intracellular enzymes, as well as the rate of glucose oxidation, were not altered by HELSS treatment), and nontoxic (i.e. HELSS-treated cells excluded trypan blue dye and did not leak intracellular enzymes into the medium). Collectively, these results demonstrate that HELSS blocks AVP-induced Arachidonic Acid release by specific and irreversible inhibition of calcium-independent phospholipase A2 and underscore the importance of calcium-independent phospholipase A2 in agonist-induced Arachidonic Acid release in at least some cell types.
Hatem Tallima - One of the best experts on this subject based on the ideXlab platform.
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Arachidonic Acid: Physiological roles and potential health benefits – A review
Elsevier, 2018Co-Authors: Hatem Tallima, Rashika El RidiAbstract:It is time to shift the Arachidonic Acid (ARA) paradigm from a harm-generating molecule to its status of polyunsaturated fatty Acid essential for normal health. ARA is an integral constituent of biological cell membrane, conferring it with fluidity and flexibility, so necessary for the function of all cells, especially in nervous system, skeletal muscle, and immune system. Arachidonic Acid is obtained from food or by desaturation and chain elongation of the plant-rich essential fatty Acid, linoleic Acid. Free ARA modulates the function of ion channels, several receptors and enzymes, via activation as well as inhibition. That explains its fundamental role in the proper function of the brain and muscles and its protective potential against Schistosoma mansoni and S. haematobium infection and tumor initiation, development, and metastasis. Arachidonic Acid in cell membranes undergoes reacylation/deacylation cycles, which keep the concentration of free ARA in cells at a very low level and limit ARA availability to oxidation. Metabolites derived from ARA oxidation do not initiate but contribute to inflammation and most importantly lead to the generation of mediators responsible for resolving inflammation and wound healing. Endocannabinoids are oxidation-independent ARA derivatives, critically important for brain reward signaling, motivational processes, emotion, stress responses, pain, and energy balance. Free ARA and metabolites promote and modulate type 2 immune responses, which are critically important in resistance to parasites and allergens insult, directly via action on eosinophils, basophils, and mast cells and indirectly by binding to specific receptors on innate lymphoid cells. In conclusion, the present review advocates the innumerable ARA roles and considerable importance for normal health. Keywords: Arachidonic Acid, Ion channels, Schistosomicide, Endotumoricide, Lipoxin A4, Endocannabinoid
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Arachidonic Acid physiological roles and potential health benefits a review
Journal of Advanced Research, 2017Co-Authors: Hatem Tallima, Rashika El RidiAbstract:It is time to shift the Arachidonic Acid (ARA) paradigm from a harm-generating molecule to its status of polyunsaturated fatty Acid essential for normal health. ARA is an integral constituent of biological cell membrane, conferring it with fluidity and flexibility, so necessary for the function of all cells, especially in nervous system, skeletal muscle, and immune system. Arachidonic Acid is obtained from food or by desaturation and chain elongation of the plant-rich essential fatty Acid, linoleic Acid. Free ARA modulates the function of ion channels, several receptors and enzymes, via activation as well as inhibition. That explains its fundamental role in the proper function of the brain and muscles and its protective potential against Schistosoma mansoni and S. haematobium infection and tumor initiation, development, and metastasis. Arachidonic Acid in cell membranes undergoes reacylation/deacylation cycles, which keep the concentration of free ARA in cells at a very low level and limit ARA availability to oxidation. Metabolites derived from ARA oxidation do not initiate but contribute to inflammation and most importantly lead to the generation of mediators responsible for resolving inflammation and wound healing. Endocannabinoids are oxidation-independent ARA derivatives, critically important for brain reward signaling, motivational processes, emotion, stress responses, pain, and energy balance. Free ARA and metabolites promote and modulate type 2 immune responses, which are critically important in resistance to parasites and allergens insult, directly via action on eosinophils, basophils, and mast cells and indirectly by binding to specific receptors on innate lymphoid cells. In conclusion, the present review advocates the innumerable ARA roles and considerable importance for normal health.
Rashika El Ridi - One of the best experts on this subject based on the ideXlab platform.
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Arachidonic Acid: Physiological roles and potential health benefits – A review
Elsevier, 2018Co-Authors: Hatem Tallima, Rashika El RidiAbstract:It is time to shift the Arachidonic Acid (ARA) paradigm from a harm-generating molecule to its status of polyunsaturated fatty Acid essential for normal health. ARA is an integral constituent of biological cell membrane, conferring it with fluidity and flexibility, so necessary for the function of all cells, especially in nervous system, skeletal muscle, and immune system. Arachidonic Acid is obtained from food or by desaturation and chain elongation of the plant-rich essential fatty Acid, linoleic Acid. Free ARA modulates the function of ion channels, several receptors and enzymes, via activation as well as inhibition. That explains its fundamental role in the proper function of the brain and muscles and its protective potential against Schistosoma mansoni and S. haematobium infection and tumor initiation, development, and metastasis. Arachidonic Acid in cell membranes undergoes reacylation/deacylation cycles, which keep the concentration of free ARA in cells at a very low level and limit ARA availability to oxidation. Metabolites derived from ARA oxidation do not initiate but contribute to inflammation and most importantly lead to the generation of mediators responsible for resolving inflammation and wound healing. Endocannabinoids are oxidation-independent ARA derivatives, critically important for brain reward signaling, motivational processes, emotion, stress responses, pain, and energy balance. Free ARA and metabolites promote and modulate type 2 immune responses, which are critically important in resistance to parasites and allergens insult, directly via action on eosinophils, basophils, and mast cells and indirectly by binding to specific receptors on innate lymphoid cells. In conclusion, the present review advocates the innumerable ARA roles and considerable importance for normal health. Keywords: Arachidonic Acid, Ion channels, Schistosomicide, Endotumoricide, Lipoxin A4, Endocannabinoid
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Arachidonic Acid physiological roles and potential health benefits a review
Journal of Advanced Research, 2017Co-Authors: Hatem Tallima, Rashika El RidiAbstract:It is time to shift the Arachidonic Acid (ARA) paradigm from a harm-generating molecule to its status of polyunsaturated fatty Acid essential for normal health. ARA is an integral constituent of biological cell membrane, conferring it with fluidity and flexibility, so necessary for the function of all cells, especially in nervous system, skeletal muscle, and immune system. Arachidonic Acid is obtained from food or by desaturation and chain elongation of the plant-rich essential fatty Acid, linoleic Acid. Free ARA modulates the function of ion channels, several receptors and enzymes, via activation as well as inhibition. That explains its fundamental role in the proper function of the brain and muscles and its protective potential against Schistosoma mansoni and S. haematobium infection and tumor initiation, development, and metastasis. Arachidonic Acid in cell membranes undergoes reacylation/deacylation cycles, which keep the concentration of free ARA in cells at a very low level and limit ARA availability to oxidation. Metabolites derived from ARA oxidation do not initiate but contribute to inflammation and most importantly lead to the generation of mediators responsible for resolving inflammation and wound healing. Endocannabinoids are oxidation-independent ARA derivatives, critically important for brain reward signaling, motivational processes, emotion, stress responses, pain, and energy balance. Free ARA and metabolites promote and modulate type 2 immune responses, which are critically important in resistance to parasites and allergens insult, directly via action on eosinophils, basophils, and mast cells and indirectly by binding to specific receptors on innate lymphoid cells. In conclusion, the present review advocates the innumerable ARA roles and considerable importance for normal health.