Close Functional Coupling between Ca2+ Release-activated Ca2+ Channels, Arachidonic Acid Release, and Leukotriene C4 Secretion

Chang, Wei Chiao; Parekh, Anant B.

doi:10.1074/jbc.m403969200

Cited by 80 publications

(64 citation statements)

References 37 publications

(64 reference statements)

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“…However, the production of cysteinyl LTC 4 , an arachidonatemetabolizing product, which depends entirely on an increased intracellular Ca 2ϩ level and MAPK (47,48), was unaffected in Ndrg1 Ϫ/Ϫ BMMCs after coculture (Fig. 8C).…”

Section: Impaired Maturation and Reduced Exocytotic Degranulation Of mentioning

confidence: 99%

Impaired Mast Cell Maturation and Degranulation and Attenuated Allergic Responses in Ndrg1-Deficient Mice

Taketomi

Sunaga²,

Tanaka

et al. 2007

The Journal of Immunology

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We have previously reported that N-myc downstream regulated gene-1 (NDRG1) is an early inducible protein during the maturation of mouse bone marrow-derived mast cells (BMMCs) toward a connective tissue mast cell-like phenotype. To clarify the function of NDRG1 in mast cells and allergic responses, we herein analyzed mast cell-associated phenotypes of mice lacking the Ndrg1 gene. Allergic responses including IgE-mediated passive systemic and cutaneous anaphylactic reactions were markedly attenuated in Ndrg1-deficient mice as compared with those in wild-type mice. In Ndrg1-deficient mice, dermal and peritoneal mast cells were decreased in number and morphologically abnormal with impaired degranulating ability. Ex vivo, Ndrg1-deficient BMMCs cocultured with Swiss 3T3 fibroblasts in the presence of stem cell factor, a condition that facilitates the maturation of BMMCs toward a CTMC-like phenotype, displayed less exocytosis than replicate wild-type cells after the cross-linking of FcεRI or stimulation with compound 48/80, even though the exocytotic response of IL-3-maintained, immature BMMCs from both genotypes was comparable. Unlike degranulation, the production of leukotriene and cytokines by cocultured BMMCs was unaffected by NDRG1 deficiency. Taken together, the altered phenotypes of Ndrg1-deficient mast cells both in vivo and ex vivo suggest that NDRG1 has roles in the terminal maturation and effector function (degranulation) of mast cells.

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Section: Impaired Maturation and Reduced Exocytotic Degranulation Of mentioning

confidence: 99%

Impaired Mast Cell Maturation and Degranulation and Attenuated Allergic Responses in Ndrg1-Deficient Mice

Taketomi

Sunaga²,

Tanaka

et al. 2007

The Journal of Immunology

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“…Ca 2ϩ influx through CRAC channels activates cPLA 2 indirectly, via recruitment of conventional protein kinase C␣ and ␤I isozymes and subsequent stimulation of the mitogen activated protein kinases ERK1 and ERK2 (13). Arachidonic acid liberated by cPLA 2 is then converted to the proinflammatory paracrine signal leukotriene C 4 (LTC 4 ) by the 5-lipoxygenase enzyme (12,13).…”

Section: N Eukaryotic Cells Camentioning

confidence: 99%

“…Defective CRAC channel activity has been causally linked to inherited primary immunodeficiencies (7) and Ca 2ϩ entry through CRAC channels regulates exocytosis (8), gene transcription (9), and cytoplasmic enzymes such as NO synthase (10), adenylate cyclase (11), and Ca 2ϩ -dependent phospholipase A 2 (cPLA 2 ; Ref. 12). Ca 2ϩ influx through CRAC channels activates cPLA 2 indirectly, via recruitment of conventional protein kinase C␣ and ␤I isozymes and subsequent stimulation of the mitogen activated protein kinases ERK1 and ERK2 (13).…”

Section: N Eukaryotic Cells Camentioning

confidence: 99%

All-or-None Activation of CRAC Channels by Agonist Elicits Graded Responses in Populations of Mast Cells

Chang

Capite

Nelson

et al. 2007

The Journal of Immunology

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In nonexcitable cells, receptor stimulation evokes Ca2+ release from the endoplasmic reticulum stores followed by Ca2+ influx through store-operated Ca2+ channels in the plasma membrane. In mast cells, store-operated entry is mediated via Ca2+ release-activated Ca2+ (CRAC) channels. In this study, we find that stimulation of muscarinic receptors in cultured mast cells results in Ca2+-dependent activation of protein kinase Cα and the mitogen activated protein kinases ERK1/2 and this is required for the subsequent stimulation of the enzymes Ca2+-dependent phospholipase A2 and 5-lipoxygenase, generating the intracellular messenger arachidonic acid and the proinflammatory intercellular messenger leukotriene C4. In cell population studies, ERK activation, arachidonic acid release, and leukotriene C4 secretion were all graded with stimulus intensity. However, at a single cell level, Ca2+ influx was related to agonist concentration in an essentially all-or-none manner. This paradox of all-or-none CRAC channel activation in single cells with graded responses in cell populations was resolved by the finding that increasing agonist concentration recruited more mast cells but each cell responded by generating all-or-none Ca2+ influx. These findings were extended to acutely isolated rat peritoneal mast cells where muscarinic or P2Y receptor stimulation evoked all-or-none activation of Ca2+entry but graded responses in cell populations. Our results identify a novel way for grading responses to agonists in immune cells and highlight the importance of CRAC channels as a key pharmacological target to control mast cell activation.

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“…Recent studies indicate that the extent of Ca 2ϩ entry through the SOCE pathway determines the activity of Ca 2ϩ -dependent cytosolic phospholipase A2 (cPLA2) (37). Upon activation and translocation to intracellular membranes, cPLA2 generates and releases arachidonic acid from membrane phospholipids (38).…”

Section: Hucp4 Regulates Soce At the Level Of Mitochondrial Ca 2ϩmentioning

confidence: 99%

Mitochondrial Uncoupling Protein-4 Regulates Calcium Homeostasis and Sensitivity to Store Depletion-induced Apoptosis in Neural Cells

Chan

Liu

Kyriazis

et al. 2006

Journal of Biological Chemistry

101

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An increase in the cytoplasmic-free Ca2؉ concentration mediates cellular responses to environmental signals that influence a range of processes, including gene expression, motility, secretion of hormones and neurotransmitters, changes in energy metabolism, and apoptosis. Mitochondria play important roles in cellular Ca 2؉ homeostasis and signaling, but the roles of specific mitochondrial proteins in these processes are unknown. Uncoupling proteins (UCPs) are a family of proteins located in the inner mitochondrial membrane that can dissociate oxidative phosphorylation from respiration, thereby promoting heat production and decreasing oxyradical production. Here we show that UCP4, a neuronal UCP, influences store-operated Ca

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Close Functional Coupling between Ca2+ Release-activated Ca2+ Channels, Arachidonic Acid Release, and Leukotriene C4 Secretion

Cited by 80 publications

References 37 publications

Impaired Mast Cell Maturation and Degranulation and Attenuated Allergic Responses in Ndrg1-Deficient Mice

Impaired Mast Cell Maturation and Degranulation and Attenuated Allergic Responses in Ndrg1-Deficient Mice

All-or-None Activation of CRAC Channels by Agonist Elicits Graded Responses in Populations of Mast Cells

Mitochondrial Uncoupling Protein-4 Regulates Calcium Homeostasis and Sensitivity to Store Depletion-induced Apoptosis in Neural Cells

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