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101.
Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14. 总被引:48,自引:0,他引:48
R S Ames H M Sarau J K Chambers R N Willette N V Aiyar A M Romanic C S Louden J J Foley C F Sauermelch R W Coatney Z Ao J Disa S D Holmes J M Stadel J D Martin W S Liu G I Glover S Wilson D E McNulty C E Ellis N A Elshourbagy U Shabon J J Trill D W Hay E H Ohlstein D J Bergsma S A Douglas 《Nature》1999,401(6750):282-286
Urotensin-II (U-II) is a vasoactive 'somatostatin-like' cyclic peptide which was originally isolated from fish spinal cords, and which has recently been cloned from man. Here we describe the identification of an orphan human G-protein-coupled receptor homologous to rat GPR14 and expressed predominantly in cardiovascular tissue, which functions as a U-II receptor. Goby and human U-II bind to recombinant human GPR14 with high affinity, and the binding is functionally coupled to calcium mobilization. Human U-II is found within both vascular and cardiac tissue (including coronary atheroma) and effectively constricts isolated arteries from non-human primates. The potency of vasoconstriction of U-II is an order of magnitude greater than that of endothelin-1, making human U-II the most potent mammalian vasoconstrictor identified so far. In vivo, human U-II markedly increases total peripheral resistance in anaesthetized non-human primates, a response associated with profound cardiac contractile dysfunction. Furthermore, as U-II immunoreactivity is also found within central nervous system and endocrine tissues, it may have additional activities. 相似文献
102.
王元丰 《北京交通大学学报(自然科学版)》1999,(1):2
基于在低速移动荷载或静力荷载作用下,多跨连续曲梁各跨峰值挠度相等的原则,给出了多跨连续曲梁在静力荷载作用下优化跨度及在动力荷载作用下近于优化跨度的取值,并对近于优化跨度的三跨连续曲梁,采用逆向搜索法首次获得其自由振动率及模态的解析解.对比试验曲梁的试验结果与计算结果,两者吻合十分良好,证明所得结果的正确性 相似文献
103.
Nitric oxide and cellular respiration 总被引:7,自引:0,他引:7
Brunori M Giuffrè A Sarti P Stubauer G Wilson MT 《Cellular and molecular life sciences : CMLS》1999,56(7-8):549-557
The role of nitric oxide (NO) as a signalling molecule involved in many pathophysiological processes (e.g., smooth muscle relaxation, inflammation, neurotransmission, apoptosis) has been elaborated during the last decade. Since NO has also been found to inhibit cellular respiration, we review here the available information on the interactions of NO with cytochrome c oxidase (COX), the terminal enzyme of the respiratory chain. The effect of NO on cellular respiration is first summarized to present essential evidence for the fact that NO is a potent reversible inhibitor of in vivo O2 consumption. This information is then correlated with available experimental evidence on the reactions of NO with purified COX. Finally, since COX has been proposed to catalyze the degradation of NO into either nitrous oxide (N2O) or nitrite, we consider the putative role of this enzyme in the catabolism of NO in vivo. 相似文献
104.
Inoue K Khajavi M Ohyama T Hirabayashi S Wilson J Reggin JD Mancias P Butler IJ Wilkinson MF Wegner M Lupski JR 《Nature genetics》2004,36(4):361-369
The molecular mechanisms by which different mutations in the same gene can result in distinct disease phenotypes remain largely unknown. Truncating mutations of SOX10 cause either a complex neurocristopathy designated PCWH or a more restricted phenotype known as Waardenburg-Shah syndrome (WS4; OMIM 277580). Here we report that although all nonsense and frameshift mutations that cause premature termination of translation generate truncated SOX10 proteins with potent dominant-negative activity, the more severe disease phenotype, PCWH, is realized only when the mutant mRNAs escape the nonsense-mediated decay (NMD) pathway. We observe similar results for truncating mutations of MPZ that convey distinct myelinopathies. Our experiments show that triggering NMD and escaping NMD may cause distinct neurological phenotypes. 相似文献
105.
106.
Xiao B Jing C Wilson JR Walker PA Vasisht N Kelly G Howell S Taylor IA Blackburn GM Gamblin SJ 《Nature》2003,421(6923):652-656
Acetylation, phosphorylation and methylation of the amino-terminal tails of histones are thought to be involved in the regulation of chromatin structure and function. With just one exception, the enzymes identified in the methylation of specific lysine residues on histones (histone methyltransferases) belong to the SET family. The high-resolution crystal structure of a ternary complex of human SET7/9 with a histone peptide and cofactor reveals that the peptide substrate and cofactor bind on opposite surfaces of the enzyme. The target lysine accesses the active site of the enzyme and the S-adenosyl-l-methionine (AdoMet) cofactor by inserting its side chain into a narrow channel that runs through the enzyme, connecting the two surfaces. Here we show from the structure and from solution studies that SET7/9, unlike most other SET proteins, is exclusively a mono-methylase. The structure indicates the molecular basis of the specificity of the enzyme for the histone target, and allows us to propose a model for the methylation reaction that accounts for the role of many of the residues that are invariant across the SET family. 相似文献
107.
108.
109.
David M. Wilson III Anton Simeonov 《Cellular and molecular life sciences : CMLS》2010,67(21):3621-3631
APE1 is a multifunctional protein that possesses several nuclease activities, including the ability to incise at apurinic/apyrimidinic
(AP) sites in DNA or RNA, to excise 3′-blocking termini from DNA ends, and to cleave at certain oxidized base lesions in DNA.
Pre-clinical and clinical data indicate a role for APE1 in the pathogenesis of cancer and in resistance to DNA-interactive
drugs, particularly monofunctional alkylators and antimetabolites. In an effort to improve the efficacy of therapeutic compounds,
such as temozolomide, groups have begun to develop high-throughput screening assays and to identify small molecule inhibitors
against APE1 repair nuclease activities. It is envisioned that such inhibitors will be used in combinatorial treatment paradigms
to enhance the efficacy of DNA-interactive drugs that introduce relevant cytotoxic DNA lesions. In this review, we summarize
the current state of the efforts to design potent and selective inhibitors against APE1 AP site incision activity. 相似文献
110.