Abstract:
:An important step in the cascade leading to neuronal cell death is degradation of laminin and other components of the brain extracellular matrix by microglia-derived proteases. Excitotoxic cell death of murine hippocampal neurones in vivo can be prevented by inhibitors of tissue plasminogen activator (tPA) or by inhibitors of plasmin. Plasmin is a potent activator of the matrix metalloproteinases (MMPs), which are made by resident and recruited leukocytes following CNS injury. In this study, we show, using Taqman RT-PCR, that MMP mRNAs, but not other calcium-dependent proteases such as calpain mRNAs, are acutely up-regulated after an excitotoxic challenge in vivo. alpha(2)-antiplasmin or BB-3103, a broad-spectrum inhibitor of the MMPs, co-injected with kainic acid into the striatum, inhibits excitotoxic cell death in the rat striatum, and reduces both the number of recruited macrophages and the size of the lesion. We also show that leukocyte populations differentially express MMPs, which may account, in part, for the expression profile we observe in the challenged brain. Our results show that inhibition of the MMPs in the rat will prevent kainic acid-induced cell death in the brain. These studies suggest that MMP inhibitors have therapeutic potential for use in stroke, and support the increasing evidence that microglial activation may contribute to neuronal cell death.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Campbell SJ,Finlay M,Clements JM,Wells G,Miller KM,Perry VH,Anthony DCdoi
10.1111/j.1471-4159.2004.02441.xkeywords:
subject
Has Abstractpub_date
2004-06-01 00:00:00pages
1378-86issue
6eissn
0022-3042issn
1471-4159pii
JNC2441journal_volume
89pub_type
杂志文章abstract::We demonstrate that 1-methyl-4-phenylpyridinium (MPP+) is toxic to chick peripheral sympathetic neurons maintained in culture in the presence of nerve growth factor (NGF). When MPP+ was added to the culture medium at the time the neurons were plated, cell loss after 3 days in culture was evident at concentrations as l...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1996.67020557.x
更新日期:1996-08-01 00:00:00
abstract::Previous evidence has suggested that brain catecholamine levels are important in the regulation of central angiotensin II receptors. In the present study, the effects of norepinephrine and 3,4-dihydroxyphenylethylamine (dopamine) on angiotensin II receptor regulation in neuronal cultures from rat hypothalamus and brai...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1986.tb00729.x
更新日期:1986-10-01 00:00:00
abstract::Ala and Gly substitutions for Pro 101 (P101) located in transmembrane domain 2 of the dopamine transporter (DAT) abolished transport activity but did not disrupt plasma membrane expression. Due to the high conservation of P101 in all neurotransmitter transporters and the capability of Pro to add flexibility to helices...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2005.03196.x
更新日期:2005-07-01 00:00:00
abstract::The endogenous neuropeptide N-acetyl-L-aspartyl-L-glutamate (NAAG) fulfills several criteria required to be accepted as a neurotransmitter. NAAG inactivation may proceed through enzymatic hydrolysis into N-acetyl-L-aspartate and glutamate by an N-acetylated-alpha-linked acidic dipeptidase (NAALADase). Therefore, some ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1990.tb08818.x
更新日期:1990-07-01 00:00:00
abstract::Our previous studies have implicated perlecan, a specific heparan sulfate proteoglycan, in the pathogenesis of fibrillar beta-amyloid protein (A beta) accumulation and persistence in Alzheimer's disease (AD) brain. In the present investigation, we determined if perlecan mRNA was present in rodent and human brain tissu...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1996.67031132.x
更新日期:1996-09-01 00:00:00
abstract::Lewy body disease (LBD) development is enhanced by mutations in the GBA gene coding for glucocerebrosidase (GCase). The mechanism of this association is thought to involve an abnormal lysosomal system and we therefore sought to evaluate if lysosomal changes contribute to the pathogenesis of idiopathic LBD. Analysis of...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2012.07879.x
更新日期:2012-10-01 00:00:00
abstract::Amino acid and monoamine concentrations were examined in tissue extracts of caudate nucleus of genetic substrains of BALB/c mice susceptible or resistant to audiogenic seizures. Amino acids [aspartate, glutamate, glycine, taurine, serine, gamma-aminobutyric acid (GABA)], monoamines, and related metabolites were separa...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1993.tb03290.x
更新日期:1993-04-01 00:00:00
abstract::Juvenile neuronal ceroid lipofuscinosis (Batten disease) is a neurodegenerative disorder caused by mutation in CLN3. Defective autophagy and concomitant accumulation of autofluorescence enriched with mitochondrial ATP synthase subunit c were previously discovered in Cln3 mutant knock-in mice. In this study, we show th...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2010.07158.x
更新日期:2011-02-01 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::2'-Deoxycoformycin (DCF), a potent inhibitor of adenosine deaminase (ADA), is increasingly used as a tool to investigate adenosine metabolism and neuromodulation. To advance further the usefulness of DCF for studies of purines in the CNS, we determined the inhibitory potency of this compound against ADA and adenylate ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1990.tb01945.x
更新日期:1990-04-01 00:00:00
abstract::Rho kinase (ROCK) may play an important role in regulating biological events of cells, including proliferation, differentiation and survival/death. Blockade of ROCK promotes axonal regeneration and neuron survival in vivo and in vitro, thereby exhibiting potential clinical applications in spinal cord damage and stroke...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2010.06876.x
更新日期:2010-09-01 00:00:00
abstract::Heme oxygenase (HO) activity in tissue adjacent to an intracerebral hematoma may modulate cellular vulnerability to heme-mediated oxidative injury. Although HO-1 is induced after experimental intracerebral hemorrhage (ICH), the time course of this induction, its effect on tissue HO activity, and its association with o...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2007.04885.x
更新日期:2007-12-01 00:00:00
abstract::To examine whether the concentration gradient of glutamine (Gln) drives concentrative Na(+)-independent uptake of neutral amino acids (NAA) in mouse cerebral astrocytes, uptake was compared in "Gln-depleted" and "Gln-replete" cultures. Uptake (30 min in Na(+)-free buffer) of histidine, kynurenine, leucine, tyrosine, a...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1992.tb08895.x
更新日期:1992-07-01 00:00:00
abstract::Terminally differentiated PC12 cells are a useful neuron-like model for studying programmed cell death in response to nerve growth factor (NGF) deprivation. This in vitro model was used to investigate the mechanism by which cyanide-induced histotoxic hypoxia produces neuronal degeneration. Treatment of undifferentiate...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1996.67031039.x
更新日期:1996-09-01 00:00:00
abstract::The amygdala has been implicated in the neuronal sequelae of stress, although little is known about the neurochemical mechanisms underlying amygdala transmission. In vivo microdialysis was employed to measure extracellular levels of dopamine in the basolateral nucleus of the amygdala in awake rats. Once it was establi...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1999.0721088.x
更新日期:1999-03-01 00:00:00
abstract::Epilepsy is a serious neurological condition exhibiting complex pathology and deserving of more serious attention. More than 30% of people with epilepsy are not responsive to more than 20 anti-epileptic drugs currently available, reflecting an unmet clinical need for novel therapeutic strategies. Not much is known abo...
journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
doi:10.1111/jnc.14663
更新日期:2019-12-01 00:00:00
abstract::Transmitter release at high probability phasic synapses of crayfish neuromuscular junctions depresses by over 50% in 60 min when stimulated at 0.2 Hz. Inhibition of the protein phosphatase calcineurin by intracellular pre-synaptic injection of autoinhibitory peptide inhibited low-frequency depression (LFD) and resulte...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2009.05973.x
更新日期:2009-05-01 00:00:00
abstract::The decrease in receptor-stimulated cyclic AMP production after chronic ethanol exposure was suggested previously to be secondary to an ethanol-induced increase in extracellular adenosine. The present study was undertaken to ascertain whether a similar mechanism was responsible for the ethanol-induced desensitization ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1993.tb03249.x
更新日期:1993-03-01 00:00:00
abstract::The olfactory bulb is one of the most vulnerable brain regions in age-related proteinopathies. Proteinopathic stress is mitigated by the heat shock protein (Hsp) family of chaperones. Here, we describe age-related decreases in Hsc70 in the olfactory bulb of the female rat and higher levels of Hsp70 and Hsp25 in middle...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.13041
更新日期:2015-06-01 00:00:00
abstract::Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder caused by an expansion of the polyglutamine tract near the C-terminus of the MJD-1 gene product, ataxin-3. Ataxin-3 is degraded by the proteasome. However, the precise mechanism of ataxin-3 degradation remains to be elucidated. In this st...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2007.04460.x
更新日期:2007-06-01 00:00:00
abstract::Preincubation of murine neuroblastoma cells (clone N1E-115) with terbium chloride resulted in a significant potentiation of carbachol-mediated increase in cyclic GMP formation. This effect was accompanied by a shift of the peak response from 30 s to 120 s and a 6-fold decrease in carbachol concentration producing half...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1984.tb02760.x
更新日期:1984-03-01 00:00:00
abstract::The expression and distribution of mRNA encoding preproatrial natriuretic peptide (ppANP) in rat brain has been investigated by in situ hybridization of two 35S-labeled synthetic DNA oligonucleotides, based on a cDNA clone sequence that encodes rat ppANP. The highest relative concentrations of ppANP mRNA were detected...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1992.tb09434.x
更新日期:1992-08-01 00:00:00
abstract::When cultured astroglia are treated with agents that elevate intracellular cyclic AMP, they become process-bearing stellate cells and resemble differentiated astrocytes in vivo. Thrombin rapidly reversed the stellation induced by dibutyryl cyclic AMP, forskolin, or isoproterenol in cultured rat astrocytes; half-maxima...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1990.tb01228.x
更新日期:1990-05-01 00:00:00
abstract::Despite considerable efforts to unravel the role of cellular prion protein (PrP(C)) in neuronal functions, the mechanisms by which PrP(C) takes part in the homeostasis of a defined neuronal phenotype remain poorly characterized. By taking advantage of a neuroectodermal cell line (1C11) endowed with the capacity to dif...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2009.06176.x
更新日期:2009-08-01 00:00:00
abstract::Mouse monoclonal B-50 antibodies (Mabs) were screened to select a Mab that may interfere with suggested functions of B-50 (GAP-43), such as involvement in neurotransmitter release. Because the Mab NM2 reacted with peptide fragments of rat B-50 containing the unique protein kinase C (PKC) phosphorylation site at serine...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1994.62030881.x
更新日期:1994-03-01 00:00:00
abstract::Synaptosomal-associated protein of 25 kDa (SNAP-25) is thought to play a key role in vesicle exocytosis and in the control of transmitter release. However, the precise mechanisms of action as well as the regulation of SNAP-25 remain unclear. Here we show by immunoprecipitation that activation of protein kinase C (PKC)...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1999.721699.x
更新日期:1999-04-01 00:00:00
abstract::A new protein kinase modulated by S-100 (tentatively referred to as protein kinase X) was partially purified from pig brain extracts. The activity of protein kinase X, which was independent of Ca2+, was demonstrated when protamine (free base), but not protamine sulfate and other proteins (including histone), was used ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1984.tb02699.x
更新日期:1984-02-01 00:00:00
abstract::Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic condition caused by dominant loss-of-function mutations of the tumor suppressor gene NF1 that encodes neurofibromin, a negative regulator of RAS activity. Mutation analysis of NF1 located at 17q11.2 has been hampered by the large size of the gene, the hig...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.13396
更新日期:2015-12-01 00:00:00
abstract::This article reports the results of a systematic investigation of the different types of antibodies produced in the course of a long-term immunization of rats with mouse nerve growth factor (NGF). We have characterized three types of monoclonal antibodies, namely: (1) antibodies that bind to NGF and inhibit its bindin...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1988.tb10565.x
更新日期:1988-04-01 00:00:00
abstract::Therapy of malignant glioma relies on treatment with the O6 -methylating agent temozolomide (TMZ) concomitant with ionizing radiation followed by adjuvant TMZ. For the treatment of recurrences, DNA chloroethylating drugs are also used. The main killing lesion induced by these drugs is O6 -alkylguanine. Since this dama...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.14262
更新日期:2018-01-01 00:00:00