Abstract：
:Most biological effects of tissue plasminogen activator (tPA), such as fibrinolysis, are mediated by its protease activity. Recent studies, however, have demonstrated that tPA also has several protease-independent effects such as: neuroprotection, microglial activation, and promoting LTP formation. In order to gain a better understanding of how tPA affects neurons, we examined neurite outgrowth and cell survival in low density cerebrocortical neuronal culture in the presence of tPA. tPA enhanced neurite elongation and neuronal survival. tPA protease inhibitors, PAI-1 or PMSF, did not alter either effect. Consistent with neurotrophic effects, tPA activated Raf-K/ERK, PKC and PI3-K/Akt, 5-60 min after treatment. In addition, specific inhibitors of these kinases reduced tPA-induced neurite outgrowth. Interestingly, survival-promoting effect of tPA was attenuated only by PI3-K inhibitors. Activation of signaling kinases suggests that tPA activates an upstream membrane receptor. Thus far, three membrane proteins, low density lipoprotein receptor-related protein (LRP), mannose receptor (MR), and annexin-II (AII), have been identified to bind tPA. While inhibiting LRP or MR did not change tPA-induced neurite outgrowth and cell survival, inhibiting AII blocked neurotrophic effects of tPA. Taken together, our results indicate that tPA has novel, non-proteolytic neurotrophic effects on cultured cortical neurons, which are likely mediated by AII.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Lee HY,Hwang IY,Im H,Koh JY,Kim YHdoi
10.1111/j.1471-4159.2007.04417.xsubject
Has Abstractpub_date
2007-06-01 00:00:00pages
1236-47issue
5eissn
0022-3042issn
1471-4159pii
JNC4417journal_volume
101pub_type
杂志文章abstract：:After intraperitoneal injection of rats with 6-fluorotryptophan (6-FT), brain 5-hydroxytryptamine (5-HT) levels decreased exponentially over 1 h. Depletion was dose-dependent and maximum depletion was observed at 200 mg/kg. 6-FT (200 mg/kg) did not significantly alter the content of 5-hydroxyindoleacetic acid. Turnove...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1987.tb05704.x
更新日期：1987-05-01 00:00:00
abstract：:Administration of L-DOPA (50 mg/kg) elicits a significant increase in extracellular dopamine in striata of rats treated with the catecholaminergic neurotoxin 6-hydroxydopamine but not in striata of intact rats. To assess the role of dopaminergic nerve terminals in determining the effects of exogenous L-DOPA on extrace...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1994.63010108.x
更新日期：1994-07-01 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：:We have previously purified and characterized a nervous system-specific glycoprotein antigen from adult Drosophila heads, designated Nervana [nerve antigen (NRV)] and identified two separate genes coding for three different proteins. All three proteins share homology with the beta subunits of Na+,K+-ATPase from variou...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1998.71010142.x
更新日期：1998-07-01 00:00:00
abstract：:Mutations in copper/zinc superoxide dismutase (SOD1) account for 10-20% of a familial form of amyotrophic lateral sclerosis (ALS). A common feature of SOD1 mutants is abnormal aggregation of the aberrant SOD1 in neurons and glia. We now report that in ALS transgenic mouse models the constitutively expressed heat shock...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2005.03054.x
更新日期：2005-05-01 00:00:00
abstract：:Three unique 5' untranslated regions (UTRs) have been characterized for human microtubule-associated protein-2 (MAP-2) transcripts. All three UTRs shared a common 171-bp sequence adjacent to the MAP-2 coding region and then diverged upstream. The size of the unique upstream sequence was 281, 146, or 104 bp. PCR of gen...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1995.65041472.x
更新日期：1995-10-01 00:00:00
abstract：:Ischemic stress in the brain induces acute and massive neuronal death in the targeted area, which is followed by a second round of detrimental processes, called delayed neuronal death, in the neighboring areas. To test the hypothesis that transcriptional control plays a role in the pathophysiology of the postischemic ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2004.02429.x
更新日期：2004-06-01 00:00:00
abstract：:Although 3,4-dihydroxyphenylethylamine (dopamine, DA) and vasoactive intestinal peptide (VIP) have been reported to stimulate adenylate cyclase activity in the rabbit retina, possible interactions between VIP-sensitive and DA-sensitive adenylate cyclase systems have not been previously investigated. To elucidate the i...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1986.tb12955.x
更新日期：1986-01-01 00:00:00
abstract：:The influence of basement membrane proteins on cellular barrier properties of primary cultures of porcine brain capillary endothelial cells grown on permeable filter inserts has been investigated. Measurements of transcellular electrical resistance (TER) by impedance spectroscopy were performed with cells cultured on ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1998.71031151.x
更新日期：1998-09-01 00:00:00
abstract：:p-glycoprotein (p-gp) is an ATP-binding cassette transporter and its overexpression is responsible for the acquisition of the multidrug resistance phenotype in human tumors. p-gp is localized at the blood-brain barrier and is involved in brain cytoprotection. Our previous work used immunoprecipitation to show that cav...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2006.04410.x
更新日期：2007-04-01 00:00:00
abstract：:Perinatal hypoxic-ischaemic encephalopathy (HIE) occurs in 1-2 in every 1000 term infants and the devastating consequences range from cerebral palsy, epilepsy and neurological deficit to death. Cellular damage post insult occurs after a delay and is mediated by a secondary neural energy failure. AMP-activated protein ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.13034
更新日期：2015-04-01 00:00:00
abstract：:Neurodegenerative diseases such as Alzheimer's disease (AD) are characterized by an abnormal aggregation of misfolded beta-sheet rich proteins such as β-amyloid (Aβ). Various ubiquitously expressed molecular chaperones control the correct folding of cellular proteins and prevent the accumulation of harmful species. We...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.12454
更新日期：2014-02-01 00:00:00
abstract：:Hypoxic preconditioning (HP) 24 h before hypoxic-ischemic (HI) injury confers significant neuroprotection in neonatal rat brain. Recent studies have shown that the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K) intracellular signaling pathways play a role in the induction of tolerance...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2004.02324.x
更新日期：2004-04-01 00:00:00
abstract：:The C57BL/Ola (Ola) mouse is a mutant substrain in which transected axons undergo very slow Wallerian degeneration. Because axonal degradation during Wallerian degeneration is calcium dependent, we tested whether Ola axons are susceptible to calcium-mediated axonal degeneration by comparing neurofilament degradation b...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1994.62062472.x
更新日期：1994-06-01 00:00:00
abstract：:Altered aquaporin-4 (AQP4) expression has been reported in brain edema, tumors, muscular dystrophy, and neuromyelitis optica. However, the plasma membrane organization of AQP4 and its interaction with proteins such as the dystrophin-associated protein complex are not well understood. In this study, we used sucrose den...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2008.05302.x
更新日期：2008-06-01 00:00:00
abstract：:It has been suggested that release of cytochrome c (Cyt c) from mitochondria during apoptotic death is through opening of the mitochondrial permeability transition pore followed by swelling-induced rupture of the mitochondrial outer membrane. However, this remains controversial and may vary with cell type and model sy...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2002.01049.x
更新日期：2002-09-01 00:00:00
abstract：:We investigated the role of Ca(2+)-dependent protein kinases in the regulation of astrocytic cell volume. Calmodulin (CaM) antagonists were used to inhibit CaM and thus Ca2+/CaM-dependent protein kinase. The effect of these inhibitors as well as activators and inhibitors of protein kinase C (PKC) on astrocytic volume ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1992.tb10064.x
更新日期：1992-05-01 00:00:00
abstract：:Recent evidence suggests that neuronal apoptosis is the consequence of an inappropriate reentry into the cell cycle. Expression of the cell cycle gene cyclin D1, a G1-phase cell cycle regulator, was examined in primary cultures of murine cerebellar granule cells (CGCs) during kainate (KA)-mediated apoptosis. Using cul...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1998.71031325.x
更新日期：1998-09-01 00:00:00
abstract：:In order to investigate the relationship between nitric oxide-mediated regulation of mitochondrial function and excitotoxicity, the role of mitochondrial ATP synthesis and intracellular redox status on the mode of neuronal cell death was studied. Brief (5 min) glutamate (100 microM) receptor stimulation in primary cor...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2001.00276.x
更新日期：2001-04-01 00:00:00
abstract：:At present, treatment for Parkinson's disease (PD) is only symptomatic; therefore, it is important to identify new targets tackling the molecular causes of the disease. We previously found that lymphoblasts from sporadic PD patients display increased activity of the cyclin D3/CDK6/pRb pathway and higher proliferation ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.13070
更新日期：2015-06-01 00:00:00
abstract：:The monoclonal L5 antibody reacts with an N-glycosidically linked carbohydrate structure which is present on the neural cell adhesion molecule L1, neural chondroitin sulfate proteoglycans, and other not yet identified glycosylated proteins. Using this antibody, we isolated and characterized proteoglycans from adult mo...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1990.tb04931.x
更新日期：1990-11-01 00:00:00
abstract：:To further analyze the action of copper on brain synaptic mechanisms, the brain dipeptide carnosine (beta-alanyl-L-histidine) was tested in Xenopus laevis oocytes expressing the rat P2X4 or P2X7 receptors. Ten micromolar copper halved the currents evoked by ATP in both receptors; co-application of carnosine plus coppe...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.0022-3042.2001.00732.x
更新日期：2002-02-01 00:00:00
abstract：:The regional distribution of inositol 1,4,5-trisphosphate (InsP3), inositol 1,3,4,5-tetrakisphosphate (InsP4), and ryanodine binding sites has been characterised and compared in the rat brain using radioligand binding assays. Cortical [3H]InsP3 binding indicated similar positional and stereospecificity as observed in ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1993.tb13382.x
更新日期：1993-05-01 00:00:00
abstract：:Research on stem cells has developed as one of the most promising areas of neurobiology. In the beginning of the 1990s, neurogenesis in the adult brain was indisputably accepted, eliciting great research efforts. Neural stem cells in the adult mammalian brain are located in the 'neurogenic' areas of the subventricular...
journal_title：Journal of neurochemistry
pub_type： 杂志文章,评审
doi：10.1111/jnc.12084
更新日期：2013-01-01 00:00:00
abstract：:This study investigates the functioning of synaptosomal ouabain-sensitive Na+ -K+ -ATPase in cold-induced edema. During vasogenic brain edema development, the enzyme affinities for Na+ and K+ are progressively decreased paralleling the increase in the tissue water content, whereas maximal velocity of the reaction is n...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1984.tb09729.x
更新日期：1984-01-01 00:00:00
abstract：:Members of the protein kinase D (PKD) family of serine/threonine kinases are known to exert diverse roles in neuronal stress responses. Here, we show the transient activation and nuclear translocation of endogenous PKD upon oxidative stress induced by H2 O2 treatment in primary neuronal cultures. Using pharmacological...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.14131
更新日期：2017-09-01 00:00:00
abstract：:Proteoglycans (PGs) are major constituents of the extracellular matrix and have recently been proposed to contribute to synaptic plasticity. Hippocampal PGs have not yet been studied or linked to memory. The aim of the study, therefore, was to isolate and characterize rat hippocampal PGs and determine their possible r...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.12783
更新日期：2014-09-01 00:00:00
abstract：:In vitro, the transport into and release of [3H]deoxycytidine from the isolated choroid plexus, the anatomical locus of the blood-cerebrospinal fluid barrier, were studied separately. By use of the ability of nitrobenzylthioinosine (NBTI) to inhibit deoxycytidine efflux from choroid plexus, the transport of 1 microM [...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1983.tb13593.x
更新日期：1983-05-01 00:00:00
abstract：:Cysteine-string protein (Csp) is a major synaptic vesicle and secretory granule protein first discovered in Drosophila and Torpedo. Csps were subsequently identified from Xenopus, Caenorhabditis elegans, and mammalian species. It is clear from the study of a null mutant in Drosophila that Csp is required for viability...
journal_title：Journal of neurochemistry
pub_type： 杂志文章,评审
doi：10.1046/j.1471-4159.2000.0741781.x
更新日期：2000-05-01 00:00:00
abstract：:As a consequence of intracerebral hemorrhage (ICH), blood components enter brain parenchyma causing progressive damage to the surrounding brain. Unless hematoma is cleared, the reservoirs of blood continue to inflict injury to neurovascular structures and blunt the brain repair processes. Microglia/macrophages (MMΦ) r...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.12974
更新日期：2015-04-01 00:00:00
