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1.
H. Underwood 《Cellular and molecular life sciences : CMLS》1989,45(10):914-922
Summary The pineal has been identified as a major circadian pacemaker within the circadian system of a number of lower vertebrates although other pacemaking sites have been implicated as well. The rhythmic synthesis and secretion of the pineal hormone, melatonin, is suggested as the mechanism by which the pineal controls circadian oscillators located elsewhere. Both light and temperature cycles can entrain the pineal melatonin rhythm. The pineal, therefore, acts as a photo and thermoendocrine transducer which functions to synchronize internal cycle with cycles in the environment. A model is presented which portrays the pineal as a major component of a multioscillator circadian system and which suggests how these multiple circadian clocks are coupled to each other and to cycles of light and temperature in the external world. 相似文献
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Nitrosamines in cigarette smoke condensate 总被引:1,自引:0,他引:1
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Summary Early suppression, followed by a period of enhancement and finally, suppression, was seen when the spleen cell response to T and B cell mitogens was monitored during growth of an adenovirus 12-induced tumour in CBA black mice. The macrophage content of the tumour changed with time and these fluctuations correlated with the ability of tumour tissue extracts to enhance the normal spleen cell response to mitogen.Acknowledgments. Thanks are dur to the Yorkshire Cancer Research Campaign, and the Cancer Research Committee of Sheffield University for financial support, also to Professor C.W. Potter for advice. 相似文献
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A thyromimetic that decreases plasma cholesterol levels without increasing cardiac activity 总被引:4,自引:0,他引:4
A H Underwood J C Emmett D Ellis S B Flynn P D Leeson G M Benson R Novelli N J Pearce V P Shah 《Nature》1986,324(6096):425-429
A number of agents that mimic the ability of the thyroid hormone, T3, to decrease plasma cholesterol levels are described; one is as effective as T3 at reducing cholesterol levels and stimulating liver function, but has very little effect on cardiac function and is thus less likely to be toxic. The agent may be useful in the treatment of atherosclerosis. 相似文献
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Howitz KT Bitterman KJ Cohen HY Lamming DW Lavu S Wood JG Zipkin RE Chung P Kisielewski A Zhang LL Scherer B Sinclair DA 《Nature》2003,425(6954):191-196
In diverse organisms, calorie restriction slows the pace of ageing and increases maximum lifespan. In the budding yeast Saccharomyces cerevisiae, calorie restriction extends lifespan by increasing the activity of Sir2 (ref. 1), a member of the conserved sirtuin family of NAD(+)-dependent protein deacetylases. Included in this family are SIR-2.1, a Caenorhabditis elegans enzyme that regulates lifespan, and SIRT1, a human deacetylase that promotes cell survival by negatively regulating the p53 tumour suppressor. Here we report the discovery of three classes of small molecules that activate sirtuins. We show that the potent activator resveratrol, a polyphenol found in red wine, lowers the Michaelis constant of SIRT1 for both the acetylated substrate and NAD(+), and increases cell survival by stimulating SIRT1-dependent deacetylation of p53. In yeast, resveratrol mimics calorie restriction by stimulating Sir2, increasing DNA stability and extending lifespan by 70%. We discuss possible evolutionary origins of this phenomenon and suggest new lines of research into the therapeutic use of sirtuin activators. 相似文献
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Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass
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Disulphide bonds in secreted proteins are considered to be inert because of the oxidizing nature of the extracellular milieu. An exception to this rule is a reductase secreted by tumour cells that reduces disulphide bonds in the serine proteinase plasmin. Reduction of plasmin initiates proteolytic cleavage in the kringle 5 domain and release of the tumour blood vessel inhibitor angiostatin. New blood vessel formation or angiogenesis is critical for tumour expansion and metastasis. Here we show that the plasmin reductase isolated from conditioned medium of fibrosarcoma cells is the glycolytic enzyme phosphoglycerate kinase. Recombinant phosphoglycerate kinase had the same specific activity as the fibrosarcoma-derived protein. Plasma of mice bearing fibrosarcoma tumours contained several-fold more phosphoglycerate kinase, as compared with mice without tumours. Administration of phosphoglycerate kinase to tumour-bearing mice caused an increase in plasma levels of angiostatin, and a decrease in tumour vascularity and rate of tumour growth. Our findings indicate that phosphoglycerate kinase not only functions in glycolysis but is secreted by tumour cells and participates in the angiogenic process as a disulphide reductase. 相似文献