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41.
Dan J Sillence 《BMC cell biology》2001,2(1):24-3
Background
Recent evidence suggests that the activation of a non-specific lipid scramblase during apoptosis induces the flipping of sphingomyelin from the cell surface to the cytoplasmic leaftet of the plasma membrane. Inner leaflet sphingomyelin is then cleaved to ceramide by a neutral sphingomyelinase. The production of this non-membrane forming lipid induces blebbing of the plasma membrane to aid rapid engulfment by professional phagocytes. However contrary evidence suggests that cells which are deficient in acid sphingomyelinase are defective in apoptosis signalling. This data has been interpreted as support for the activation of acid sphingomyelinase as an early signal in apoptosis.Hypothesis
An alternative explanation is put forward whereby the accumulation of intracellular sphingomyelin in sphingomyelinase deficient cells leads to the formation of intracellular rafts which lead to the sequestration of important signalling molecules that are normally present on the cell surface where they perform their function.Testing the hypothesis
It is expected that the subcellular distribution of important signalling molecules is altered in acid sphingomyelinase deficient cells, leading to their sequestration in late endosomes / lysosomes. Other sphingolipid storage diseases such as Niemann-Pick type C which have normal acid sphingomyelinase activity would also be expected to show the same phenotype.Implications of the hypothesis
If true the hypothesis would provide a mechanism for the pathology of the sphingolipid storage diseases at the cellular level and also have implications for the role of ceramide in apoptosis. 相似文献42.
Ryall JG Gregorevic P Plant DR Sillence MN Lynch GS 《American journal of physiology. Regulatory, integrative and comparative physiology》2002,283(6):R1386-R1394
Potential treatments for skeletal muscle wasting and weakness ideally possess both anabolic and ergogenic properties. Although the beta(2)-adrenoceptor agonist clenbuterol has well-characterized effects on skeletal muscle, less is known about the therapeutic potential of the related beta(2)-adrenoceptor agonist fenoterol. We administered an equimolar dose of either clenbuterol or fenoterol to rats for 4 wk to compare their effects on skeletal muscle and tested the hypothesis that fenoterol would produce more powerful anabolic and ergogenic effects. Clenbuterol treatment increased fiber cross-sectional area (CSA) by 6% and maximal isometric force (P(o)) by 20% in extensor digitorum longus (EDL) muscles, whereas fiber CSA in soleus muscles decreased by 3% and P(o) was unchanged, compared with untreated controls. In the EDL muscles, fenoterol treatment increased fiber CSA by 20% and increased P(o) by 12% above values achieved after clenbuterol treatment. Soleus muscles of fenoterol-treated rats exhibited a 13% increase in fiber CSA and a 17% increase in P(o) above that of clenbuterol-treated rats. These data indicate that fenoterol has greater effects on the functional properties of rat skeletal muscles than clenbuterol. 相似文献
43.
Beitzel F Sillence MN Lynch GS 《American journal of physiology. Endocrinology and metabolism》2007,293(4):E932-E940
Stimulating the beta-adrenoceptor (beta-AR) signaling pathway can enhance the functional repair of skeletal muscle after injury, but long-term use of beta-AR agonists causes beta-AR downregulation, which may limit their therapeutic effectiveness. The aim was to examine beta-AR signaling during early regeneration in rat fast-twitch [extensor digitorum longus (EDL)] and slow-twitch (soleus) muscles after bupivacaine injury and test the hypothesis that, during regeneration, beta-agonist administration does not cause beta-AR desensitization. Rats received either the beta-AR agonist fenoterol (1.4 mgxkg(-1)xday(-1) ip) or saline for 7 days postinjury. Fenoterol reduced beta-AR density in regenerating soleus muscles by 42%. Regenerating EDL muscles showed a threefold increase in beta-AR density, and, again, these values were 43% lower with fenoterol treatment. An amplified adenylate cyclase (AC) response to isoproterenol was observed in cell membrane fragments from EDL and soleus muscles 7 days postinjury. Fenoterol attenuated this increase in regenerating EDL muscles but not soleus muscles. beta-AR signaling mechanisms were assessed using AC stimulants (NaF, forskolin, and Mn(2+)). Although beta-agonist treatment reduces beta-AR density in regenerating muscles, these muscles can produce large cAMP responses relative to healthy (uninjured) muscles. Desensitization of beta-AR signaling in regenerating muscles is prevented by altered rates of beta-AR synthesis and/or degradation, changes in G protein populations and coupling efficiency, and altered AC activity. These mechanisms have important therapeutic implications for modulating beta-AR signaling to enhance muscle repair after injury. 相似文献
44.
于2000~2004年对武陵山东部7个不同样地、3个不同海拔梯度和6个不同生境类型的蚤类,进行了5年调查与研究.结果:1)在获得的7科17属30种4 320只蚤类中,有4种为古北界种类,占13.33%,22种为东洋界种类,占73.34%,4种为广布种,占13.33%;该结果与云南无量山及临沧地区的蚤类有着相同或相似的区系渊源,而与一江之隔的大巴山东部地区区系则明显不同,该地区以古北界成分为优势;2)武陵山东部地区蚤类的垂直分布规律主要表现在,1 100 m以下主要为东洋界成分,1 200 m以上有少量古北界种类分布,并随海拔升高,古北界成分略有增加;3)在7个不同样地中,物种丰富度和个体数量随海拔升高而增加,在优势种上,多数样地以偏远古蚤为优势,但在优势数量上缺乏明显规律性,并不是随海拔升高而增加;4)在6个不同生境类型中,优势种与优势数量都具明显的规律性,其中以偏远古蚤为主分为两组,山脊侧缘林、小溪山边林和坡地林为一组,人工林和农田山侧灌木林为另一组,前者平均优势数量达80.03%,后者优势数量在31.56%~48.92%之间;5)相似性系数(q值):在整个山体多数样地中,由北向南相似性系数(q值)随海拔降低和空间距离增大而逐渐降低,仅绿丛坡与牛庄、绿丛坡与独岭有例外,表明整个山体植被的片断化、或斑块化,一方面加剧或减低了样地与样地之间蚤类群落的相似程度,另一方面还要受海拔及空间距离的双重影响与制约,即海拔高度和空间距离愈大,蚤类群落的相似性及多样性越低,山体的片断、斑块或破碎化就越明显,这显然与人为过多或过频干扰有关. 相似文献
45.
Hungerford NL Sortais B Smart CG McKinney AR Ridley DD Stenhouse AM Suann CJ Munn KJ Sillence MN McLeod MD 《The Journal of steroid biochemistry and molecular biology》2005,96(3-4):317-334
Due to the potential for misuse of a wide range of anabolic steroids in horse racing, a screening test to detect multiple compounds, via a common class of metabolites, would be a valuable forensic tool. An enzyme-linked immunosorbent assay (ELISA) has been developed to detect 17alpha-alkyl anabolic steroid metabolites in equine urine. 16beta-Hydroxymestanolone (16beta,17beta-dihydroxy-17alpha-methyl-5alpha-androstan-3-one) was synthesised in six steps from commercially available epiandrosterone (3beta-hydroxy-5alpha-androstan-17-one). Polyclonal antibodies were raised in sheep, employing mestanolone (17beta-hydroxy-17alpha-methyl-5alpha-androstan-3-one) or 16beta-hydroxymestanolone conjugated to human serum albumin, via a 3-carboxymethyloxime linker, as antigens. Antibody cross-reactivities were determined by assessing the ability of a library of 54 representative steroids to competitively bind the antibodies. Antibodies raised against 16beta-hydroxymestanolone showed excellent cross-reactivities for all of the 16beta,17beta-dihydroxy-17alpha-methyl steroids analysed and an ELISA has been developed to detect these steroid metabolites. Using this 16beta-hydroxymestanolone assay, urine samples from horses administered with stanozolol (17alpha-methyl-pyrazolo[4',3':2,3]-5alpha-androstan-17beta-ol), were analysed raw, following beta-glucuronidase hydrolysis, and following solid-phase extraction (SPE) procedures. The suppressed absorbances observed were consistent with detection of the metabolite 16beta-hydroxystanozolol. Positive screening results were confirmed by comparison with standard LCMS analyses. Antibodies raised against mestanolone were also used to develop an ELISA and this was used to detect metabolites retaining the parent D-ring structure following methandriol (17alpha-methylandrost-5-ene-3beta,17beta-diol) administration. The ELISA methods developed have application as primary screening tools for detection of new and known anabolic steroid metabolites. 相似文献
46.
Gregorevic P Ryall JG Plant DR Sillence MN Lynch GS 《American journal of physiology. Heart and circulatory physiology》2005,289(1):H344-H349
Although beta-adrenoceptor agonists have clinical merit for attenuating the age-related loss of skeletal muscle mass and strength (sarcopenia), potential cardiac-related side effects may limit their clinical application. The aim of this study was to determine whether chronic beta-agonist administration impairs cardiac function in adult or aged rats. Adult (16 mo) and aged (28 mo) Fischer 344 rats were treated with fenoterol (1.4 mg.kg(-1).day(-1) ip) or vehicle for 4 wk. Heart function was assessed in vitro before analyses of cardiac structure and beta-adrenoceptor density. Heart mass increased 17% and 25% in fenoterol-treated adult and aged rats, respectively. The increased heart mass in aged, but not adult, rats was associated with a relative increase in collagen content. Cardiac hypertrophy in adult rats was associated with an increase in left ventricular developed pressure, a marked reduction in cardiac output, and a reduction in coronary flow per unit heart mass. In contrast, negligible differences in ventricular function were observed in fenoterol-treated aged rats. The differential effect on contractile function was not associated with age-related differences in beta-adrenoceptor density but, rather, an age-related increase in downregulation after treatment. Our results show that chronic beta-agonist treatment impairs cardiac function to a greater extent in adult than in aged rats. These results provide important information regarding the potential effects of chronic beta-agonist use on cardiac function and the future development of safe and effective treatments for sarcopenia. 相似文献
47.
Sophia R. Cameron-Christie Constance F. Wells Marleen Simon Marja Wessels Candy Z.N. Tang Wenhua Wei Riku Takei Coranne Aarts-Tesselaar Sarah Sandaradura David O. Sillence Marie-Pierre Cordier Hermine E. Veenstra-Knol Matteo Cassina Kathrin Ludkig Eva Trevisson Melanie Bahlo David M. Markie Zandra A. Jenkins Stephen P. Robertson 《American journal of human genetics》2018,102(6):1115-1125
48.
We have used glycol methacrylate to study undecalcified skeletal growth plate and subchondral bone. Minor modifications of the original technique including dehydration in glycol methacrylate vacuum infiltration and polymerization in the cold make it quite suitable for embedding of such tisssues. Moreover, specimens can be processed quickly and the morphologic and biochemical integrity of the tissue retained so that histochemical procedures can be readily applied. Collagen, glycosaminoglycan, glycogen, lipid, calcium and the activity of alkaline and acid phosphatase were localized. This technique appears to be very useful for studying skeletal tissues. 相似文献
49.
MÁRCIO R. VELOSO FRANCELINO ADRIANA DE LIMA MENDONÇA RUTH R. DO NASCIMENTO FERNANDO A. C. DE MENDONÇA EDLEIDE L. DA SILVA MARIA DO ROSÁRIO T. DE FREITAS CYRO R. CABRAL JR CARLOS EDUARDO DA SILVA JOSÉ H. S. RIBEIRO ANTÔNIO EUZÉBIO G. SANTANA 《Physiological Entomology》2008,33(1):37-42
Abstract. Ethological studies are conducted under laboratory conditions using workers of Atta sexdens sexdens and Atta opaciceps collected from field colonies to investigate the mechanisms involved in the alarm response and intra-specific recognition in leaf-cutting ants. Hexane extracts from the heads of gardeners and generalist workers elicit higher levels of alarm response in foragers from the same colony than do mandibular gland extracts from foragers and soldiers, indicating that gardeners, generalists and foragers are primarily responsible for the production of alarm pheromone. Foragers subjected to extracts from non-nestmates exhibit significantly greater alarm responses than are induced by similar extracts derived from nestmate workers, suggesting that the alarm pheromone may have a role in nestmate recognition. 相似文献
50.
PHUC T. DO PIERRE BALDET GUILLAUME MENARD CHRISTOPHE ROTHAN CAPUCINE MASSOT HÉLÈNE GAUTIER JAWAD AARROUF ALISDAIR R. FERNIE REBECCA STEVENS 《Plant, cell & environment》2013,36(1):159-175
The regulation of carbon allocation between photosynthetic source leaves and sink tissues in response to stress is an important factor controlling plant yield. Ascorbate oxidase is an apoplastic enzyme, which controls the redox state of the apoplastic ascorbate pool. RNA interference was used to decrease ascorbate oxidase activity in tomato (Solanum lycopersicum L.). Fruit yield was increased in these lines under three conditions where assimilate became limiting for wild‐type plants: when fruit trusses were left unpruned, when leaves were removed or when water supply was limited. Several alterations in the transgenic lines could contribute to the improved yield and favour transport of assimilate from leaves to fruits in the ascorbate oxidase lines. Ascorbate oxidase plants showed increases in stomatal conductance and leaf and fruit sugar content, as well as an altered apoplastic hexose : sucrose ratio. Modifications in gene expression, enzyme activity and the fruit metabolome were coherent with the notion of the ascorbate oxidase RNAi lines showing altered sink strength. Ascorbate oxidase may therefore be a target for strategies aimed at improving water productivity in crop species. 相似文献