Abstract:
:Interleukin-1β (IL-1β) is released from activated microglia and involved in the neurodegeneration of acute and chronic brain disorders, such as stroke and Alzheimer's disease, in which extracellular acidification has been shown to occur. Here, we examined the extracellular acidic pH regulation of IL-1β production, especially focusing on TDAG8, a major proton-sensing G-protein-coupled receptor, in mouse microglia. Extracellular acidification inhibited lipopolysaccharide -induced IL-1β production, which was associated with the inhibition of IL-1β cytoplasmic precursor and mRNA expression. The IL-1β mRNA and protein responses were significantly, though not completely, attenuated in microglia derived from TDAG8-deficient mice compared with those from wild-type mice. The acidic pH also stimulated cellular cAMP accumulation, which was completely inhibited by TDAG8 deficiency. Forskolin and a cAMP derivative, which specifically stimulates protein kinase A (PKA), mimicked the proton actions, and PKA inhibitors reversed the acidic pH-induced IL-1β mRNA expression. The acidic pH-induced inhibitory IL-1β responses were accompanied by the inhibition of extracellular signal-related kinase and c-Jun N-terminal kinase activities. The inhibitory enzyme activities in response to acidic pH were reversed by the PKA inhibitor and TDAG8 deficiency. We conclude that extracellular acidic pH inhibits lipopolysaccharide-induced IL-1β production, at least partly, through the TDAG8/cAMP/PKA pathway, by inhibiting extracellular signal-related kinase and c-Jun N-terminal kinase activities, in mouse microglia.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Jin Y,Sato K,Tobo A,Mogi C,Tobo M,Murata N,Ishii S,Im DS,Okajima Fdoi
10.1111/jnc.12661subject
Has Abstractpub_date
2014-05-01 00:00:00pages
683-95issue
4eissn
0022-3042issn
1471-4159journal_volume
129pub_type
杂志文章abstract::Leptinotoxin-h (LPTx), a neurotoxin (otherwise designated beta-leptinotarsin-h) known to stimulate the release of neurotransmitters from synapses, was purified from the hemolymph of the potato beetle, Leptinotarsa haldemani, by a simplification of the procedure originally developed by Crosland et al. [Biochemistry 23,...
journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1985.tb12913.x
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journal_title:Journal of neurochemistry
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更新日期:1997-09-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1985.tb07218.x
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1983.tb11307.x
更新日期:1983-02-01 00:00:00
abstract::The beta-amyloid peptide (Abeta) is considered responsible for the pathogenesis of Alzheimer's disease. Despite the magnitude of reports describing a neurotoxic role of extracellular Abeta, the role for intracellular Abeta (iAbeta) has not been elucidated. We previously demonstrated that in rat pheochromocytoma cells ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:1968-08-01 00:00:00
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pub_type: 杂志文章
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更新日期:2005-03-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1980.tb06276.x
更新日期:1980-08-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1987.tb09995.x
更新日期:1987-10-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:2001-05-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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journal_title:Journal of neurochemistry
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doi:10.1046/j.1471-4159.2001.00095.x
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journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:1984-12-01 00:00:00
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pub_type: 杂志文章,评审
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:1988-12-01 00:00:00
abstract::Transient exposure to ethanol (EtOH) results in a massive neurodegeneration in the developing brain leading to behavioral and cognitive deficits observed in fetal alcohol syndrome. There is now compelling evidence that K+ channels play an important role in the control of programmed cell death. The aim of the present w...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2009.06197.x
更新日期:2009-08-01 00:00:00
abstract::Binding of tetanus toxin to rat brain membranes was of lower affinity and capacity when binding was determined in 150 mM NaCl, 50 mM Tris-HCl (pH 7.4) than in 25 mM Tris-acetate (pH 6.0). Binding under both conditions was reduced by treating the membranes with neuraminidase. Pronase treatment, however, reduced toxin b...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:1986-07-01 00:00:00
abstract::Recently, in the course of our search for the prostacyclin receptor in the brain, we found a novel subtype, designated as IP2, which was finely discriminated by use of the specific ligand (15R)-16-m-tolyl-17,18,19,20-tetranorisocarbacyclin (15R-TIC) and specifically localized in the rostral part of the brain. In the p...
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更新日期:1999-06-01 00:00:00