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91.
Abstract: K252a, an inhibitor of trk phosphorylation and nerve growth factor signal transduction in PC12 cells, blocked nerve growth factor-induced responses in cultured adult rat dorsal root ganglion sensory neurones. The nerve growth factor-dependent appearance of capsaicin sensitivity and accumulation of the neuropeptide substance P were inhibited when dorsal root ganglion neurones were grown in the presence of low concentrations (100 n M ) of K252a. At higher concentrations (3 µ M ), however, K252a stimulated the development of capsaicin sensitivity and the accumulation of substance P even in the absence of nerve growth factor. By using a wide dose range, therefore, we showed that K252a could either inhibit or mimic nerve growth factor's actions on sensory neurones. These results may explain the apparent paradox in the literature that some groups show a blocking effect of K252a on nerve growth factor-dependent survival of dorsal root ganglion sensory neurones, whereas others report that K252a can substitute for nerve growth factor or other trophic factors and promote neuronal survival. 相似文献
92.
Effect of Hypoxia on Na+-K+-Cl− Cotransport in Cultured Brain Capillary Endothelial Cells of the Rat
Abstract: The effect of hypoxia on Na+,K+-ATPase and Na+-K+-Cl? cotransport activity in cultured rat brain capillary endothelial cells (RBECs) was investigated by measuring 86Rb+ uptake as a tracer for K+. RBECs expressed both Na+,K+-ATPase and Na+-K+-Cl? cotransport activity (4.6 and 5.5 nmol/mg of protein/min, respectively). Hypoxia (24 h) decreased cellular ATP content by 43.5% and reduced Na+,K+-ATPase activity by 38.9%, whereas it significantly increased Na+-K+-Cl? cotransport activity by 49.1% in RBECs. To clarify further the mechanism responsible for these observations, the effect of oligomycin-induced ATP depletion on these ion transport systems was examined. Exposure of RBECs to oligomycin led to a time-dependent decrease of cellular ATP content (by ~65%) along with a complete inhibition of Na+,K+-ATPase and a coordinated increase of Na+-K+-Cl? cotransport activity (up to 100% above control values). Oligomycin augmentation of Na+-K+-Cl? cotransport activity was not observed in the presence of 2-deoxy-d -glucose (a competitive inhibitor of glucose transport and glycolysis) or in the absence of glucose. These results strongly suggest that under hypoxic conditions when Na+,K+-ATPase activity is reduced, RBECs have the ability to increase K+ uptake through Na+-K+-Cl? cotransport. 相似文献
93.
Kazuhito Hisatsune Seiichi Kondo Takehiro Iguchi Teruyo Ito Keiichi Hiramatsu 《Microbiology and immunology》1996,40(9):621-626
Structural and serological studies were performed with the lipopolysaccharide (LPS) expressed by Escherichia coli K12 strains No. 30 and No. 64, into which cosmid clones derived from Vibrio cholerae O1 NIH 41 (Ogawa) and NIH 35A3 (Inaba) had been introduced, respectively. The two recombinant strains, No. 30 (Ogawa) and No. 64 (Inaba), produced LPS that included, in common, the O-polysaccharide chain composed of an α(1 → 2)-linked N-(3-deoxy-L -glycero-tetronyl)-D -perosamine (4-amino-4,6-dideoxy-D -manno-pyranose) homopolymer attached to the core oligosaccharide of the LPS of E. coli K12. Structural analysis revealed the presence of N-(3-deoxy-L -glycero-tetronyl)-2-O-methyl-D -perosamine at the non-reducing terminus of the O-polysaccharide chain of LPS from No. 30 (Ogawa) but not from No. 64 (Inaba). Serological analysis revealed that No. 30 (Ogawa) and No. 64 (Inaba) LPS were found to share the group antigen factor A of V. cholerae O1. They were distinguished by presence of the Ogawa antigen factor B [co-existing with relatively small amounts of the Inaba antigen factor (c)] in the former LPS and the Inaba antigen factor C in the latter LPS. It appears, therefore, that No. 30 (Ogawa) and No. 64 (Inaba) have O-antigenic structures that are fully consistent with the AB(c) structure for the Ogawa and the AC structure for the Inaba O-forms of V. cholerae O1, respectively. Thus, the present study clearly confirmed our previous finding that the Ogawa antigenic factor B is substantially related to the 2-O-methyl group at the non-reducing terminus of the α(1 → 2)-linked N-(3-deoxy-L -glycero-tetronyl)-D -perosamine homopolymer that forms the O-polysaccharide chain of LPS of V. cholerae O1 (Ogawa). 相似文献
94.
Adenovirus type 35 (Ad35) is an important pathogen in immunosuppressed individuals such as AIDS patients and bone marrow transplant recipients. Ad35, a member of Ad subgroup B, differs with respect to pathogenic properties from the more fully characterized subgroup C Ad, such as Ad2 and Ad5. One region of human Ad which varies between subgroups and which may influence Ad pathogenesis is early region 3 (E3), a region which appears to modulate the immune response to Ad infection. In order to begin to characterize the differences between the Ad35 E3 and the E3 of other Ad, the complete DNA sequence of the Ad35 E3 promoter and coding sequence along with two flanking structural proteins, pVIII and fiber, has been determined. Ad35 contains open reading frames which are unique to the subgroup B Ad in addition to the four characterized immunoregulatory proteins encoded by the subgroup C Ad. Further evaluation of the sequence of one of these proteins, 18.5K, which is the class-I major histocompatibility complex (MHC) binding protein of 18.5 kDa, demonstrates that the amino acid sequence of this Ad2 gp19K homologue fits a proposed model of gp19K-MHC interaction. Analysis of promoter sequences demonstrates that an NF-κB site found in the subgroup C E3 promoter is absent from the Ad35 E3 promoter. In addition, the fiber genes of Ad35 and other subgroup B Ad have been shown to diverge in an unexpected way, yielding three clusters of fiber homology. 相似文献
95.
96.
High-conductance calcium-activated potassium channels; Structure,pharmacology, and function 总被引:19,自引:0,他引:19
Gregory J. Kaczorowski Hans -Günther Knaus Reid J. Leonard Owen B. McManus Maria L. Garcia 《Journal of bioenergetics and biomembranes》1996,28(3):255-267
High-conductance calcium-activated potassium (maxi-K) channels comprise a specialized family of K+ channels. They are unique in their dual requirement for depolarization and Ca2+ binding for transition to the open, or conducting, state. Ion conduction through maxi-K channels is blocked by a family of venom-derived peptides, such as charybdotoxin and iberiotoxin. These peptides have been used to study function and structure of maxi-K channels, to identify novel channel modulators, and to follow the purification of functional maxi-K channels from smooth muscle. The channel consists of two dissimilar subunits, and . The subunit is a member of theslo Ca2+-activated K+ channel gene family and forms the ion conduction pore. The subunit is a structurally unique, membrane-spanning protein that contributes to channel gating and pharmacology. Potent, selective maxi-K channel effectors (both agonists and blockers) of low molecular weight have been identified from natural product sources. These agents, together with peptidyl inhibitors and site-directed antibodies raised against and subunit sequences, can be used to anatomically map maxi-K channel expression, and to study the physiologic role of maxi-K channels in various tissues. One goal of such investigations is to determine whether maxi-K channels represent novel therapeutic targets. 相似文献
97.
脱氧雪腐镰刀菌烯醇对K~+刺激的小麦根质膜ATP酶活性、K~+吸收、外渗及再分配的影响 总被引:1,自引:0,他引:1
10-8mol/L的DON毒素加入小麦根质膜制剂中可促进K+刺激的ATP酶活力,10-6mol/L开始呈抑制效应,抑制程度随DON浓度加大而提高。根尖(5cm)离体根段于0.5mmol/L的KCl中,10-8mol/L的DON能促进根段K+吸收,10-6mol/L以上浓度则K+吸收呈抑制,10-2mol/L浓度下根段的净吸收为负值,表明组织中K+大量外渗。根段置蒸馏水中6h,4mmol/L的DON即导致振段K+渗漏。用DON处理整株小麦根,浓度在0.25mmol/L以上可促进K+从植株其它部位向根运输,而浓度在8mmol/L时即抑制K+向根富集,且根内K+明显渗漏。 相似文献
98.
Elena Kosenko Yuri Kaminsky Eugenio Grau María-Dolores Miñana Goizane Marcaida Santiago Grisolía Vicente Felipo 《Journal of neurochemistry》1994,63(6):2172-2178
Abstract: Injection of large doses of ammonia into rats leads to depletion of brain ATP. However, the molecular mechanism leading to ATP depletion is not clear. The aim of the present work was to assess whether ammonium-induced depletion of ATP is mediated by activation of the NMDA receptor. It is shown that injection of MK-801, an antagonist of the NMDA receptor, prevented ammonia-induced ATP depletion but did not prevent changes in glutamine, glutamate, glycogen, glucose, and ketone bodies. Ammonia injection increased Na+ ,K+ -ATPase activity by 76%. This increase was also prevented by previous injection of MK-801. The molecular mechanism leading to activation of the ATPase was further studied. Na+ ,K+ -ATPase activity in samples from ammonia-injected rats was normalized by "in vitro" incubation with phorbol 12-myristate 13-acetate, an activator of protein kinase C. The results obtained suggest that ammonia-induced ATP depletion is mediated by activation of the NMDA receptor, which results in decreased protein kinase C-mediated phosphorylation of Na+ ,K+ -ATPase and, therefore, increased activity of the ATPase and increased consumption of ATP. 相似文献
99.
In a controlled animal experiment the effects of dietary subacute Zn deficiency on growth, Zn concentration, and tissue 42-K
distribution were studied. Growth retardation caused lower body weight because both skeletal and heart muscle showed a reduction
in cell mass. Zn concentrations were reduced in most tissues, however, they remained unaltered in heart muscle. 42-K activity
increased in skeletal muscle and pancreas. We hypothesize the latter reflects the organs rate of metabolism, inducing the
exocrine pancreas to increase Zn absorption; in skeletal muscle it may induce also alterations in cell potentiation, causing
restless behavior. As suggested by the calculated specific K activity (Bq/mol), the K uptake was highest in liver and bone,
high in pancreas and skeletal muscle and low in heart muscle. The latter suggests K retention in heart muscle. Specific activity
in plasma and jejunum remained unaltered: K status and absorption seem unaffected. Zn deficiency causes different 42-K activities
in the various tissues, that respond by alterations in K metabolism without the induction of K deficiency. 相似文献
100.
Abstract: Methylmercury (MeHg) increases the concentration of intracellular Ca2+ ([Ca2+]i) and another endogenous polyvalent cation in both synaptosomes and NG108-15 cells. In synaptosomes, the elevation in [Ca2+]i was strictly dependent on extracellular Ca2+ (Ca2+e); similarly, in NG108-15 cells, a component of the elevations in [Ca2+]i was Ca2+e dependent. The MeHg-induced elevations in endogenous polyvalent cation concentration were independent of Ca2+e in synaptosomes and NG108-15 cells. The pattern of alterations in fura-2 fluorescence suggested the endogenous polyvalent cation may be Zn2+. Using 19F-NMR spectroscopy of rat cortical synaptosomes loaded with the fluorinated chelator 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N′,N′-tetraacetic acid (5F-BAPTA), we have determined unambiguously that MeHg increases the free intrasynaptosomal Zn2+ concentration ([Zn2+]i). In buffer containing 200 µM EGTA to prevent the Ca2+e-dependent elevations in [Ca2+]i, the [Zn2+]i was 1.37 ± 0.20 nM; following a 40-min exposure to MeHg-free buffer [Zn2+]i was 1.88 ± 0.53 nM. Treatment of synaptosomes for 40 min with 125 µM MeHg yielded [Zn2+]i of 2.69 ± 0.55 nM, whereas 250 µM MeHg significantly elevated [Zn2+]i to 3.99 ± 0.68 nM. No Zn2+ peak was observed in synaptosomes treated with the cell-permeant heavy metal chelator N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN, 100 µM) following 250 µM MeHg exposure. [Ca2+]i in buffer containing 200 µM EGTA was 338 ± 26 nM and was 370 ± 64 nM following an additional 40-min exposure to MeHg-free buffer. [Ca2+]i was 498 ± 28 or 492 ± 53 nM during a 40-min exposure to 125 or 250 µM MeHg, respectively. None of the values of [Ca2+]i differed significantly from either pretreatment levels or buffer-treated controls. 相似文献