Abstract:
:Rho family GTPases promote the survival of certain neuronal populations. However, pro-survival and pro-death signaling pathways regulated downstream of Rho GTPases are largely unknown. Cerebellar granule neurons (CGNs) exposed to Clostridium difficile toxin B (ToxB), a monoglucosyltransferase that specifically inhibits Rho GTPases, die by a mitochondrial apoptotic cascade. Using a high-throughput immunoblotting screen (BD Powerblot), we found that ToxB markedly reduced the expression of Rac1 and c-Raf, upstream components of a Rac-dependent mitogen-activated protein (MAP) kinase pathway. Moreover, ToxB rapidly suppressed a p21-activated kinase/MAP kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)1/2 signaling cascade that normally promotes degradation of the Bcl-2 homology-3 (BH3)-only protein Bim, a key initiator of mitochondrial apoptosis. In contrast to c-Raf down-regulation, ToxB enhanced expression of the transcription factor, signal transducer and activator of transcription-1 (STAT1). Both STAT1 up-regulation and apoptosis induced by ToxB were prevented by a pan-inhibitor of Janus kinases (JAKs), indicating that JAK/STAT signaling was pro-apoptotic in CGNs. Most significantly, direct inhibition of MEK was sufficient to trigger JAK-dependent STAT1 expression, suggesting that cross-talk between MEK/ERK and JAK/STAT pathways plays a key role in regulating neuronal survival. Finally, ERK dephosphorylation and STAT1 up-regulation induced by ToxB were mimicked by a dominant-negative (N17) mutant of Rac1. These data suggest that the MEK/ERK cascade functions downstream of Rac GTPase to actively repress pro-apoptotic JAK/STAT signaling in healthy CGNs.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Loucks FA,Le SS,Zimmermann AK,Ryan KR,Barth H,Aktories K,Linseman DAdoi
10.1111/j.1471-4159.2006.03802.xsubject
Has Abstractpub_date
2006-05-01 00:00:00pages
957-67issue
4eissn
0022-3042issn
1471-4159pii
JNC3802journal_volume
97pub_type
杂志文章abstract::The effect of cerebral hypoxia-ischemia (HI) on levels and tyrosine phosphorylation of the NMDA receptor was examined in 7- (P7) and 21 (P21)-day-old rats. Unilateral HI was administered by ligation of the right common carotid artery and exposure to an atmosphere of 8% O2/92% N2 for 2 (P7) or 1.5 (P21) h. This duratio...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2002.01026.x
更新日期:2002-08-01 00:00:00
abstract::Tetanus and botulinum toxins bind and are internalized at the neuromuscular junction. Botulinum neurotoxins (BoNTs) enter the cytosol at the motor nerve terminal; tetanus neurotoxin (TeNT) proceeds retroaxonally inside the motor axon to reach the spinal cord inhibitory interneurons. Although the major target of BoNTs ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1999.0730372.x
更新日期:1999-07-01 00:00:00
abstract::Proteasomal dysfunction has been recently implicated in the pathogenesis of several neurodegenerative diseases, including Parkinson's disease and diffuse Lewy body disease. We have developed an in vitro model of proteasomal dysfunction by applying pharmacological inhibitors of the proteasome, lactacystin or ZIE[O-tBu]...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2001.00474.x
更新日期:2001-08-01 00:00:00
abstract::Parkinson's disease (PD) is a movement disorder with widespread neurodegeneration in the brain. Significant oxidative, reductive, metabolic, and proteotoxic alterations have been observed in PD postmortem brains. The alterations of mitochondrial function resulting in decreased bioenergetic health is important and need...
journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
doi:10.1111/jnc.14308
更新日期:2018-03-01 00:00:00
abstract::Over 25 years ago it was first reported that intracellular chloride levels (Cl-in ) were higher in developing neurons than in maturity. This finding has had significant implications for understanding the excitability of developing networks and recognizing the underlying causes of hyperexcitability associated with dise...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.13936
更新日期:2017-03-01 00:00:00
abstract::The neural cell adhesion molecule L1 is a phosphorylated, integral membrane glycoprotein that is recovered from adult mouse brain tissue by immunoaffinity chromatography as a set of polypeptides with apparent molecular masses of 200, 180, 140, and 80 kilodaltons (L1-200, L1-180, L1-140, and L1-80, respectively). It ha...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1988.tb02941.x
更新日期:1988-02-01 00:00:00
abstract::Spiroxatrine has been reported to be a 5-HT1A serotonin receptor antagonist. Therefore [3H]spiroxatrine was synthesized and its 5-HT1A receptor binding properties in homogenates of rat hippocampal membranes were characterized with the expectation that it would be the first 5-HT1A antagonist radioligand. [3H]8-Hydroxyd...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1988.tb02943.x
更新日期:1988-02-01 00:00:00
abstract::The novel N-methyl-D-aspartate receptor channel ligand (+)-[3H]5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5, 10-imine maleate ([3H]MK-801) has been utilized to label this receptor in human brain tissue. Characteristics of [3H]MK-801 binding to well-washed membranes from 17 control subjects and 16 patients with...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1989.tb11760.x
更新日期:1989-09-01 00:00:00
abstract::Based on our initial finding that the nitric oxide (NO) sensitive fluorochrome diaminofluorescein (DAF) was localized to mitochondria in cultured primary neurons, we investigated whether brain mitochondria produce NO through a mitochondrial NO synthase (mtNOS) enzyme. Isolated brain mitochondria were loaded with DAF a...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2004.02553.x
更新日期:2004-08-01 00:00:00
abstract::Mouse models of MPTP intoxication have been used extensively to explore the molecular mechanisms of Parkinson's disease. However, these models present some limitations since; (i) Dopaminergic (DA) cell death occurs rapidly in contrast to the presumably slow evolution of the disease process. (ii) Some of the key histol...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2008.05651.x
更新日期:2008-11-01 00:00:00
abstract::As a basis for attempts to define the structures of the proteins within myelin, methods have been developed for their extraction and isolation in solutions of non-denaturing detergents. With use of solutions of deoxycholate or Triton X-100, up to 90% of the protein has been extracted from bovine CNS myelin, along with...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1984.tb02679.x
更新日期:1984-02-01 00:00:00
abstract::The characteristics of beta-alanine transport at the blood-brain barrier were studied by using primary cultured bovine brain capillary endothelial cells. Kinetic analysis of the beta-[3H]alanine transport indicated that the transporter for beta-alanine functions with Kt of 25.3 +/- 2.5 microM and Jmax of 6.90 +/- 0.48...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1996.67010330.x
更新日期:1996-07-01 00:00:00
abstract::Protein synthesis in the brain is known to be affected by a wide range of treatments. The detailed analysis of the mechanisms that are involved would be facilitated by the development of cell-free translation systems derived from brain tissue. To date, brain cell-free systems have not been fully characterized to demon...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1981.tb01696.x
更新日期:1981-03-01 00:00:00
abstract::Serotonin S2, benzodiazepine, and muscarinic receptors showed different regional distributions in the human brain but were present in all cortical areas. The laminar distributions of [3H]ketanserin, [3H]diazepam, and [3H]quinuclidinylbenzilate were investigated in the temporal cortex and revealed a high density in the...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1984.tb12845.x
更新日期:1984-10-01 00:00:00
abstract::We used both the polymerase chain reaction (PCR) and in situ hybridization to search for the presence of proteolipid protein (PLP) gene transcripts in the developing mouse. Total brain RNA extracted from 13-19-day embryos, analyzed by PCR, demonstrated the presence of a single transcript that was unambiguously identif...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1992.tb09378.x
更新日期:1992-03-01 00:00:00
abstract::Enzymes considered to be markers for neurons (angiotensin converting enzyme, thermolysin-like metalloendopeptidase, alanine aminopeptidase, and glutamate-oxaloacetate transaminase), glia (glutamine synthetase, pyruvate carboxylase, and beta-glucuronidase), and endothelial cells (alkaline phosphatase and plasminogen ac...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1986.tb04539.x
更新日期:1986-08-01 00:00:00
abstract::Mutations in Parkin, an E3 ligase, which participates in the ubiquitin-proteasome system (UPS), cause juvenile onset Parkinson's disease (PD). Some mutants aggregate upon over-expression, but the effects of such aggregation on the UPS and neuronal survival have not been characterized. We show in this study that transi...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2007.04620.x
更新日期:2007-08-01 00:00:00
abstract::In an established rat model of penetrating ballistic-like brain injury (PBBI), arylsulfatase B (ARSB; N-acetylgalactosamine 4-sulfatase) activity was significantly reduced at the ipsilateral site of injury, but unaffected at the contralateral site or in sham controls. In addition, the ARSB substrate chondroitin 4-sulf...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.13156
更新日期:2015-08-01 00:00:00
abstract::Incubation of beta-endorphin with cytosolic and particulate fractions of rat brain resulted in the formation of several peptides, including gamma-endorphin [beta-endorphin-(1-17)] and beta-endorphin-(18-31), indicating the presence of enzyme activity cleaving the Leu17-Phe18 bond of beta-endorphin. An assay for this L...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1989.tb07249.x
更新日期:1989-06-01 00:00:00
abstract::The proposed structural protein of peripheral nerve myelin, P0, has been shown to have several covalent modifications. In addition to being glycosylated, sulfated, and acylated, P0 is phosphorylated, with the intracellular site of this latter addition being in question. By employing nerve injury models that exhibit di...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1987.tb02448.x
更新日期:1987-12-01 00:00:00
abstract::Rabbit retinas were maintained in a physiological state in vitro and exposed to 0.5-h pulses of labeled leucine. Protein synthesis was determined from incorporation of the label, and degradation from its subsequent release. The retinas were treated as test-control pairs. The control retina remained in darkness while t...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1980.tb12499.x
更新日期:1980-07-01 00:00:00
abstract::The alpha-synuclein (Snca) gene is expressed at higher levels in alcohol-naïve, inbred alcohol-preferring (iP) rats than in alcohol-non preferring (iNP) rats. Snca modulates dopamine transmission and the dopamineregic system, which play a role in mediating the rewarding properties of alcohol consumption. Thus, underst...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2006.04111.x
更新日期:2006-10-01 00:00:00
abstract::The dose-dependent effects of two putative gamma-aminobutyric acid (GABA)-ergic agonists, muscimol and 4,5,6,7-tetrahydroisoxazolo(4,5-e)-pyridin-3-ol (THIP), upon local cerebral glucose utilisation in 60 discrete regions of the CNS have been examined in conscious rats using the [14C]2-deoxyglucose quantitative autora...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1982.tb07937.x
更新日期:1982-09-01 00:00:00
abstract::Developmental profiles were determined for the activities of eight enzymes involved in fatty acid beta-oxidation in rat brain. The enzymes studied were the palmitoyl-CoA, octanoyl-CoA, butyryl-CoA, glutaryl-CoA, and 3-hydroxyacyl-CoA dehydrogenases, the enoyl-CoA hydratase (crotonase), and the C4- and C10-thiolases. W...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1988.tb01044.x
更新日期:1988-08-01 00:00:00
abstract::F2-isoprostanes (F2-IsoPs) are well-established sensitive and specific markers of oxidative stress in vivo. Isofurans (IsoFs) are also products of lipid peroxidation, but in contrast to F2-IsoPs, their formation is favored when oxygen tension is increased in vitro or in vivo. Mitochondrial dysfunction in Parkinson's d...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2003.01709.x
更新日期:2003-05-01 00:00:00
abstract::Type 1 cannabinoid receptor (CB1) is expressed in different neuronal populations in the mammalian brain. In particular, CB1 on GABAergic or glutamatergic neurons exerts different functions and display different pharmacological properties in vivo. This suggests the existence of neuron-type specific signalling pathways ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.12137
更新日期:2013-03-01 00:00:00
abstract::We have recently isolated from bovine adrenal medulla a novel C-terminally amidated opioid peptide, amidorphin, which derives from proenkephalin A. Amidorphin revealed a widespread distribution in bovine, ovine, and porcine tissue. Particularly high concentrations of amidorphin immunoreactivity were detected in adrena...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1985.tb07218.x
更新日期:1985-11-01 00:00:00
abstract::Abstract Dorfin is a RING-finger type ubiquitin ligase for mutant superoxide dismutase 1 (SOD1) that enhances its degradation. Mutant SOD1s cause familial amyotrophic lateral sclerosis (FALS) through the gain of unelucidated toxic properties. We previously showed that the accumulation of mutant SOD1 in the mitochondri...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2003.02289.x
更新日期:2004-04-01 00:00:00
abstract::Sex differences were investigated in cholinergic neurons of the septal-diagonal band region of adult rats subjected to neonatal treatment with 3,3',5-triiodo-L-thyronine (T3). Neonatal hyperthyroidism resulted in a 44% increase in specific activity of choline acetyltransferase (ChAT; EC 2.3.1.6) in adult male rat sept...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1991.tb02570.x
更新日期:1991-01-01 00:00:00
abstract::Our results provide evidence that 6-hydroxydopamine induced, after auto-oxidation, toxic levels of hydrogen peroxide (H2O2) that caused bovine chromaffin cell toxicity and death. 6-Hydroxydopamine (6-OHDA) treatment markedly reduced, in a dose-response fashion, chromaffin cell viability. Cell death was accompanied by ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2003.01592.x
更新日期:2003-03-01 00:00:00