一氧化氮合酶的作用机制

一氧化氮合酶的作用机制赵慧卿（安徽医科大学化学教研室,合肥２３００３２）关键词一氧化氮一氧化氮合酶８０年代以来,人们发现一氧化氮在许多生理过程中起着十分重要的作用［１］。在血管内皮细胞中,一氧化氮可激活可溶性鸟苷酸环化酶（ｓＧＣ）,通过升高环鸟苷酸水...     

真菌中一氧化氮生物合成、降解及功能的研究进展

一氧化氮是一个有较高活性的自由基气体分子,无论在动植物还是微生物中,作为一个细胞内和细胞间的信号传导分子,它在许多的生理和病理过程中都发挥着双向的调节作用.研究发现真菌细胞可以合成一氧化氮,适当浓度的一氧化氮在真菌细胞内发挥多种重要的生物学功能,一旦一氧化氮过量累积,这个自由基分子会对细胞造成伤害,导致细胞凋亡.一氧化氮介导生成的环鸟苷酸(cGMP)作为一种重要的第二信使分子涉及到真菌细胞内多种信号途径的调控,调节了整个真菌类群的生长发育、形态发生、孢子形成和萌发、繁殖和细胞凋亡的过程,影响了真菌整个生命周期的生理活动.到目前为止,尽管一氧化氮在动植物中作用的机制得到了广泛的研究,但一氧化氮在真菌中的研究报道很有限.关于一氧化氮在真菌中的合成和降解途径,一氧化氮介导的信号传导机制的研究还不透彻,它在真菌细胞内的功能和毒理还有待于更深入的研究.     

软体动物的一氧化氮及其合酶的研究进展

一氧化氮作为一种重要的信息分子,参与调节软体动物的嗅觉、运动、取食、机体防御及学习行为。本文从生理、生化、形态定位以及信号转导几方面综述了有关软体动物一氧化氮及其合酶的最新研究进展。     

神经型一氧化氮合酶的活性调控

一氧化氮是重要的信使分子,在生物体内参与众多生理及病理过程。生物体内存在着复杂的一氧化氮合酶活性调控机制以精确调控一氧化氮的生成。在神经系统中,一氧化氮主要由神经型一氧化氮合酶催化生成。神经型一氧化氮合酶的活性主要受到翻译后水平上钙离子和钙调蛋白的调控,其调控方式包括二聚化、多位点的磷酸化和去磷酸化,以及主要由PDZ结构域介导的蛋白质-蛋白质相互作用。一氧化氮本身对其合酶的活性具有负反馈调控作用。近年来的研究提示,细胞质膜上的脂筏微区在神经性一氧化氮合酶的活性调控中也起到重要的调节作用。     

诱导型一氧化氮合酶与疾病

炎症是众多疾病如自体免疫紊乱、神经退行性病变、心血管疾病和癌症发展的病理机制,诱导型一氧化氮合酶在炎症过程中被诱导表达,产生过量的一氧化氮,引发炎症级联反应,进而导致以上多种疾病发生。抑制诱导型一氧化氮合酶表达在体内体外实验及临床使用中均体现抗炎效果和症状改善。本文综述了诱导型一氧化氮合酶在炎症过程中诱导表达及与各类重大疾病联系的最新进展,并展望了诱导型一氧化氮合酶抑制剂作为抗炎治疗策略的前景。     

一氧化氮与肺纤维化的研究进展

肺纤维化是一组由多种因素引起的肺间质性病变,肺纤维化的发病机制迄今尚未完全清楚。近年来,发现在哺乳动物细胞的一氧化氮合酶催化合成的一氧化氮在肺纤维化的发生发展中发挥着重要的作用。因此,阐述一氧化氮与肺纤维化的关系,有着重要的理论意义和潜在的临床应用价值。     

一氧化氮合成酶研究进展

一氧化氮以其多样的生理、病理作用和广泛的组织分布,引起国内外学的极大关注和兴趣。一氧化氮合成酶是体内催化Ｌ－精氨酸合成一氧化氮的酶,分三种类型。有关其蛋白质结构、基因结构特点、基因表达调节的研究进展迅速。     

一氧化氮:神经系统内一种新的信使分子

新近几年,一氧化氮的许多生物学活性日益被人们所认识,尤其是它在神经系统内的信息传递作用引人注目.文章综述了一氧化氮在神经系统内的生物合成、分布、信息传递功能及其机制.     

一氧化氮与植物成熟衰老的关系

植物体可以通过依赖于类似哺乳动物的一氧化氮合成酶或硝酸还原酶的酶促合成途径和非酶促合成途径产生一氧化氮。植物内源一氧化氮可以通过抑制乙烯的生物合成和调控环化核苷酸在植物组织中的水平,来延缓植物组织的成熟和衰老,延长果蔬等组织的货架期。     

一氧化氮的抗感染免疫作用及其机制

一氧化氮在机体抗感染免疫防御体系中的重要作用被发现之后,各国学者进行了大量的相关研究。这些研究证明：一氧化氮作为活化巨噬细胞的一种细胞毒效分子,在抑制和杀伤病毒,细菌,寄生虫等的免疫应答中起重要作用。一氧化氮抗感染的作用机制十分复杂,它通过调节Th1/Th2的平衡来促进机体的免疫应答,并可直接与含铁酶的Fe-S基团结合,破坏酶的活性,进而杀伤病原体及其宿主细胞。     

Partial sequence and characterization of nitric oxide synthase gene from Hyphantria cunea

Nitric oxide synthase (NOS) gene has been partially sequenced from Hyphantria cunea and compared with those already determined from insects. Hyphantria cunea NOS possesses putative recognition sites for co‐factors heme, BH₄, CaM, FMN, FAD, and NADPH common to NOS. The deduced amino acid sequence of H. cunea NOS cDNA showed 70.3% identity to Manduca sexta NOS and 57.6–69.5% identity to NOS sequences from other insects. Nitric oxide synthase is expressed in all tissues of H. cunea, except in hemocytes. The NOS expression in midgut, fat body, epidermis, and Malpighian tubule strongly increased against Gram‐positive and Gram‐negative bacterial infection. These results suggest that NOS may play an important role in insect defense system against bacterial infection.     

白细胞介素—10对血管一氧化氮／一氧化氮合酶系统的影响

为探讨抗炎因子－－白细胞介素－10（IL－10）对大鼠主动脉一氧化氮（NO）／一氧化氮合酶（NOS）系统的影响,应用Griess试剂、^3H－瓜氨酸生成及蛋白免疫印迹杂交等方法,测定IL－10孵育对血管NO释放、NOS活性及表达的影响。结果发现细菌脂多糖（LPS）呈浓度领带性地激活诱导型NOS（iNOS）,促进NO生成。IL－10（10^-10-10^-8g/ml）呈浓度依赖性地上调内皮型NOS（eNOS）蛋白表达及其活性,但对iNOS活性及表达无明显影响,IL－10（10^-9-10^-8g/ml）显著抑制10μg/ml LPS诱导的NO生成和iNOS激活;而高浓度IL－10（10^-7g/ml）则上调iNOS的活性,对eNOS蛋白的表达知活性无明显影响。因此IL－10对NO／NOS系统具有双重影响,一方面可抑制炎症介质诱发的作为炎性物质的iNOS的表达及激活,另一方面可上调内皮源扩血管物质NO的释放。     

Decrease in DEET repellency caused by nitric oxide in Rhodnius prolixus

N,N-diethyl-3-methylbenzamide (DEET) is widely used as an insect repellent; however, little is known about its mode of action. On the other hand, nitric oxide (NO) participates in the olfaction transduction pathway of insects. In this work, nitroso-acetyl-cysteine (SNAC), a nitric oxide donor, or dibutyril-cyclic-GMP (db-cGMP), the cyclic nucleotide analog, were applied on fifth instar nymphs of Rhodnius prolixus before exposing them to DEET, to obtain information about the possible role of NO/cGMP system in the olfaction process. In the first place, we exposed the nymphs to several DEET concentrations (70, 700, 1,750, and 3,500 microg/cm2). All these concentrations produced a repellent effect. A decrease in repellency during the course of the experiment was observed when the nymphs were exposed to high concentrations of DEET (700 and 1,750 microg/cm2), suggesting an adaptation phenomenon. The pre-treatment of the insects with 15 microg /insect of SNAC or 2 microg/insect of db-cGMP produced a reduction of the repellency. An increase in locomotor activity was observed in insects exposed to 350 or 700 microg/cm2 DEET. Although exposure to 70 microg/cm2 DEET produced a high repellency response, it did not modify the insects' locomotor activity. Insects treated with two doses of SNAC before being exposed to 350 microg/cm2 of DEET showed no differences in locomotor activity compared to controls.     

一氧化氮在炎性疼痛中的作用

一氧化氮（nitric oxide,NO）是细胞内重要的信使分子和神经递质,它参与多种生命活动,包括炎性疼痛.NO对炎性疼痛的发展和维持起到了重要的作用.研究NO在疼痛中所起到的作用及其机制有利于阐明痛觉生理和发现疼痛治疗的新手段.目前研究表明,脊髓水平NO参与炎性疼痛调制的可能机制主要有NO/cGMP途径、参与调控即刻早期基因、与其他神经递质的协同作用.另外研究表明,3种类型的一氧化氮合酶（nitric oxide synthases,NOS）在炎性疼痛过程中被激活或者有不同程度的增强表达.     

Activation of pig oocytes using nitric oxide donors

Nitric oxide (NO) plays an important role in intracellular signaling, but its role during the activation of mammalian oocytes is little understood. In our study, in vitro matured pig oocytes were cultured with NO-donors-S-nitroso-N-acetylpenicillamine (SNAP) or sodium nitropruside (SNP). These treatments were able to induce parthenogenetic activation of pig oocytes matured in vitro. The specificity of this effect was confirmed by the activation of oocytes by exogenous endothelial nitric oxide synthase (eNOS) microinjected in the oocyte with its activator calmodulin. Relatively long exposure (10 hr) is needed for activation of pig oocytes with 2.0 mM SNAP. An active NOS is necessary for the NO-dependent activation of pig oocytes because NOS inhibitors L-NMMA or L-NAME are able to inhibit activation of oocytes with NO-donor SNAP. On the basis of our data, we conclude that the NO-dependent activating stimulus seems inadequate because it did not induce the exocytosis of cortical granules. Also, the cleavage of parthenogenetic embryos was very low, and embryos did not develop beyond the stage of eight blastomeres.     

The language of nitric oxide signalling

Nitric oxide (NO) has recently joined the select circle of the ubiquitous molecules of plant signalling networks. Indeed, the last decade has produced a tremendous amount of data that evidence the diversity of physiological situations in which NO is involved in plants and the complexity of NO biology. These data also underline our difficulties in providing simple answers to the cardinal questions of where NO comes from and how the NO message is converted into a physiological response. The identification of NO primary targets and NO-regulated genes provides new opportunities to connect NO biochemistry and NO biology. This review summarises our current understanding of NO signalling, from the generation of the NO message to its execution into a cellular response. The review particularly considers whether and how NO may be responsible for specific signalling in different physiological processes.     

NO在脊髓痛觉传递过程中的作用

一氧化氮(nitric oxide,NO)是神经元细胞内一种新型的神经递质,它参与多种生命活动,包括脊髓水平的伤害性信息传递过程。研究NO在伤害性信息传递过程中的作用及其机制,有利于阐明痛觉生理和发现疼痛治疗的新手段。本文将NO在慢性痛脊髓伤害性信息传递中的作用及其机制的相关研究进展作一综述。     

Alternative pathways of nitric oxide formation in Lactobacilli: Evidence for nitric oxide synthase activity by EPR

The study of the ability of Lactobacillus plantarum 8P-A3 to synthesize nitric oxide (NO) showed that this strain lacks nitrite reductase. However, analysis by the EPR method revealed the presence of nitric oxide synthase activity in this strain. Like mammalian nitric oxide synthase, lactobacillar NO synthase is involved in the formation of nitric oxide from L-arginine. L. plantarum 8P-A3 does not produce NO in the denitrification process. The regulatory role of NO in symbiotic bacteria is emphasixed.     

一氧化氮对心肌的抑制性保护作用

内皮型与神经型一氧化氮合酶(eNOS,nNOS)在心肌细胞内持续表达,而细胞应激可引起诱导型NOS(iNOS)表达.心肌细胞结构型eNOS与nNOS源性NO,在生理条件下对心肌主要发挥4方面的抑制作用:减缓心肌细胞搏动频率,轻度抑制心肌细胞收缩功能,加速心肌细胞舒张并增加顺应性,以及轻度抑制线粒体电子传递而增强氧利用效...     

Decreased viability of nitric oxide synthase double knockout mice

Nitric oxide acts as an important intracellular messenger in a variety of systems, including reproduction. Previous studies have shown the importance of nitric oxide in embryo development. NO is produced from l-arginine by the enzyme, nitric oxide synthase (NOS), which has three isoforms: endothelial (NOS3), neural (NOS1), and inducible (NOS2). We hypothesize that, because of the importance of NOS in development, at least two NOS isoforms are required in order for normal embryo development to occur. Through the generation of NOS3/NOS2, NOS3/NOS1, and NOS2/NOS1 double knockout mice, we found that while litter size remains unchanged, the expected number of generated double knockout mice varies significantly from what would be predicted by Mendelian genetics. Estrous cycles were similar for both DKO and the wild-type mice, and both groups were deemed fertile by their ability to mate with wild-type (CD-1) mice. Together, these results lead us to conclude that the lack of two NOS isoforms leads to a decreased viability in mice because of a developmental problem in the double knockout embryo.