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1.
M Reboud-Ravaux 《Biochimie》1985,67(12):1197-1216
Considerable interest in plasminogen activators as human thrombolytic drugs has stimulated rapid biotechnologic progresses. These enzymes have been classified in two immunochemically distinct groups: "urokinase-like" activators or u-PA which do not interact with fibrin and "tissue activator-like" activators or t-PA which interact with fibrin. Plasminogen activators are widely distributed in normal and malignant tissues and they are implicated in various physiological and pathological processes. They maintain the functional integrity of the vascular system and their presence may be of importance in tissue remodeling and cell migration. Urokinase and streptokinase are used in human thrombolytic therapy. However, the properties displayed by t-PA suggest that this enzyme may be a superior fibrinolytic agent. The primary structures of urokinase and t-PA are known; both enzymes have been synthesized by DNA technology. In order to produce t-PA in large quantities by gene cloning, intensive studies are conducted by pharmaceutical industries. Clinical trials using t-PA for dissolving thrombi in coronary heart disease, strokes and pulmonary embolism are in progress. This review presents the molecular and structural properties of plasminogen activators, as well as related physiological, pathological and therapeutic aspects. 相似文献
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Rui-Gang Zhang Chung-Yin Yip Ke-wu Pan Meng-yun Cai Wing-Hung Ko 《Journal of cellular physiology》2020,235(11):8387-8401
We investigated the regulation of Cl− secretion by adrenoceptors in polarized 16HBE14o- human bronchial epithelial cells. Treatment with the nonselective β adrenoceptor agonist isoprenaline stimulated an increase in short-circuit current (ISC), which was inhibited by the β adrenoceptor blocker propranolol. Treatment with procaterol, an agonist specific for the β2 adrenoceptor subtype, stimulated a similar increase in ISC, which was inhibited by the β2 adrenoceptor antagonist ICI 118551. Inhibitors of cystic fibrosis transmembrane conductance regulator (CFTR) and calcium-activated Cl− channel (CaCC), but not K+ channel blockers, were able to inhibit the increase in ISC. “Trimultaneous” recording of ISC and intracellular cyclic adenosine monophosphate (cAMP) and Ca2+ levels in 16HBE14o- epithelia confirmed that the ISC induced by isoprenaline or procaterol involved both cAMP and Ca2+ signaling. Our results demonstrate that β2 adrenoceptors regulate Cl− secretion in the human airway epithelium by activating apical CFTRs and CaCCs via cAMP-dependent and intracellular Ca2+-dependent mechanisms, respectively. 相似文献
5.
A Scuto M Kirschbaum R Buettner M Kujawski J M Cermak P Atadja R Jove 《Cell death & disease》2013,4(5):e635
We explored the activity of SIRT1 activators (SRT501 and SRT2183) alone and in combination with panobinostat in a panel of malignant lymphoid cell lines in terms of biological and gene expression responses. SRT501 and SRT2183 induced growth arrest and apoptosis, concomitant with deacetylation of STAT3 and NF-κB, and reduction of c-Myc protein levels. PCR arrays revealed that SRT2183 leads to increased mRNA levels of pro-apoptosis and DNA-damage-response genes, accompanied by accumulation of phospho-H2A.X levels. Next, ChIP assays revealed that SRT2183 reduces the DNA-binding activity of both NF-κB and STAT3 to the promoter of GADD45G, which is one of the most upregulated genes following SRT2183 treatment. Combination of SRT2183 with panobinostat enhanced the anti-growth and anti-survival effects mediated by either compound alone. Quantitative-PCR confirmed that the panobinostat in combination with SRT2183, SRT501 or resveratrol leads to greater upregulation of GADD45G than any of the single agents. Panobinostat plus SRT2183 in combination showed greater inhibition of c-Myc protein levels and phosphorylation of H2A.X, and increased acetylation of p53. Furthermore, EMSA revealed that NF-κB binds directly to the GADD45G promoter, while STAT3 binds indirectly in complexes with NF-κB. In addition, the binding of NF-κB/STAT3 complexes to the GADD45G promoter is inhibited following panobinostat, SRT501 or resveratrol treatment. Moreover, the combination of panobinostat with SRT2183, SRT501 or resveratrol induces a greater binding repression than either agent alone. These data suggest that STAT3 is a corepressor with NF-κB of the GADD45G gene and provides in vitro proof-of-concept for the combination of HDACi with SIRT1 activators as a potential new therapeutic strategy in lymphoid malignancies. 相似文献
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Presynaptic α2 Adrenoceptors Inhibit Glutamate Release from Rat Spinal Cord Synaptosomes 总被引:1,自引:0,他引:1
Yoshinori Kamisaki Toshihiro Hamada Kazuhisa Maeda Masahiko Ishimura Tadao Itoh 《Journal of neurochemistry》1993,60(2):522-526
Abstract: The presynaptic regulation of amino acid release from nerve terminals was investigated using synaptosomes prepared from the rat spinal cord. The basal releases of endogenous glutamate (Glu), aspartate (Asp), and γ-amino-butyric acid (GABA) were 34.6, 21.5, and 10.0 pmol/min/mg of protein, respectively. Exposure to a depolarizing concentration of KCl (30 m M ) evoked 2.7-, 1.5-, and 2.9-fold increases in Glu, Asp, and GABA release, respectively. Clonidine reduced the K+ -evoked overflow of Glu to 56% of the control overflow with a potency (IC50 ) of 17 n M , but it did not affect K+ -evoked overflow of Asp, GABA, and their basal releases. Similarly, noradrenaline inhibited the K+ -evoked overflow of Glu, although phenylephrine and isoproterenol showed no effect. The inhibitory effect of clonidine was counteracted by α2 -adrenoceptor antagonists, rauwolscine, yohimbine, and idazoxan, regardless of the imidazoline structures. Because Glu is considered a neurotransmitter of primary afferents that transmit both nociceptive and nonnociceptive stimuli in the spinal cord, these data suggest that part of Glu release may be regulated by the noradrenergic system through α2 adrenoceptors localized on the primary afferent terminals. 相似文献
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采用放射配体结合方法观察外源性氧自由基对大鼠心肌α_1肾上腺素受体(α_1受体)及其亚型α_(1A)与α_(1B)的影响和对β肾上腺素受体(β受体)的影响。发现:(1)·OH,使α_1受体与~(125)IBE2254最大结合量(B_(max))分别下降55%与36%。(2)·OH可使α_1受体与~(125)IBE2254结合的K_d值增高171%,而对K_d值无影响。(3)·OH,均使α_1受体亚型α_(1A)与α_(1B)之间的比例增加。(4)·OH,对β受体与~(125)IPIN最大结合量B_(max)和K_d值均无影响。(5)氧自由基清除剂甘露醇或超氧化物歧化酶均可对抗氧自由基引起α_1受体及其亚型的改变。上述结果提示,氧自由基可直接作用于心肌膜,引起α_1受体数量和亲和性下降,α_1受体亚型α_(1A)与α_(1B)之间的比例改变。 相似文献
9.
Mia Dahlström Lena GE Mårtensson Per R Jonsson Thomas Arnebrant Hans Elwing 《Biofouling》2013,29(2-4):191-203
The barnacle Balanus improvisus is the major fouling macroorganism in Swedish waters and it colonizes most man‐made surfaces submerged in the sea. New or impending legislation restricts the use of traditional, hazardous antifouling coatings based on heavy metals, mainly copper and tin. This calls for the development of new non‐toxic methods that prevent barnacle settlement. In this work several adrenoceptor compounds are shown to be very efficient in preventing the settlement of cyprid larvae of B. improvisus. The settlement rate of laboratory‐reared cyprids was studied in hydrophilised polystyrene dishes containing adrenoceptor antagonists and agonists dissolved in seawater. Two of these drugs, medetomidine and clonidine, repeatedly inhibited settlement at concentrations between 1 nM and 10 nM. In the vertebrate adrenoceptor classification system, which separates pharmacological substances according to their receptor affinity, both of these substances are classified as α2 adrenoceptor agonists. An inhibiting effect on presyn‐aptic receptors is suggested, but the localization of the receptor effect requires futher studies. Experiments also revealed that the inhibiting effect of medetomidine was reversible. Cyprids incubated with medetomidine for 20 h attached and metamorphosed into juvenile barnacles after washing and transferrence to seawater. The antagonizing compound atipamezole reversed the effect of medetomidine. This observation supports the assumption that this substance acts at the receptor level. Studies of the surface affinity of medetomidine revealed a strong tendency to accumulate in solid/ liquid phase boundaries. This ability makes it particularly attractive as a candidate for the development of a slow‐release carrier in marine coatings. Panels coated with medetomidine in an acrylate polymer and exposed in the field reduced the recruitment of B. improvisus by 96% after 4 weeks and by 70% after 8 weeks. 相似文献
10.
Use of chemical activator for the management of root-knot disease in medicinal and aromatic plants can become an attractive alternative to traditionally used nematicides. Large numbers of chemical molecules are present in the plants and are involved in the induction of different types of proteins. The purpose of our research study is to explore the possibilities of resistance factors that are inherent in the plant by treating them with few chemical activators to activate against root-knot nematode infection. Efforts were made to achieve a satisfactory suppression of root-knot nematode, Meloidogyne incognita, a serious menace to successful cultivation of chamomile, Matricaria recutita L. Rauch (syn. Matricaria chamomilla L. Fain. Asteraceae) causing root-knot disease through use of different chemical activators. Here we examined selected groups of resistance activator viz. Isonicotinamide, 2-chloronicotinic acid, 5-nitrosalicylic acid, 4-chlorosalicylic acid, DL-2 aminobutyric acid, 2-aminobutyric acid, O-acetylsalicylic acid, 4-amino salicylic acid, salicylic acid and these were used as soil drench using 3 week old seedlings transplanted to root-knot nematode infested pots. Maximum reduction in root-knot severity and nematode population occurred with 4-chlorosalicylic acid, O-acetyl salicylic acid, 2-chloronicotinic acid and gave significant flower yield advantages. Present experiment suggests a strong possibility of these activators in integrated management for protection against plant parasitic nematodes. 相似文献