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Brooks NL Trent CM Raetzsch CF Flurkey K Boysen G Perfetti MT Jeong YC Klebanov S Patel KB Khodush VR Kupper LL Carling D Swenberg JA Harrison DE Combs TP 《The Journal of biological chemistry》2007,282(48):35069-35077
Glucose metabolism is altered in long-lived people and mice. Although it is clear that there is an association between altered glucose metabolism and longevity, it is not known whether this link is causal or not. Our current hypothesis is that decreased fasting glucose utilization may increase longevity by reducing oxygen radical production, a potential cause of aging. We observed that whole body fasting glucose utilization was lower in the Snell dwarf, a long-lived mutant mouse. Whole body fasting glucose utilization may be reduced by a decrease in the production of circulating glucose. Our isotope labeling analysis indicated both gluconeogenesis and glycogenolysis were suppressed in Snell dwarfs. Elevated circulating adiponectin may contribute to the reduction of glucose production in Snell dwarfs. Adiponectin lowered the appearance of glucose in the media over hepatoma cells by suppressing gluconeogenesis and glycogenolysis. The suppression of glucose production by adiponectin in vitro depended on AMP-activated protein kinase, a cell mediator of fatty acid oxidation. Elevated fatty acid oxidation was indicated in Snell dwarfs by increased utilization of circulating oleic acid, reduced intracellular triglyceride content, and increased phosphorylation of acetyl-CoA carboxylase. Finally, protein carbonyl content, a marker of oxygen radical damage, was decreased in Snell dwarfs. The correlation between high glucose utilization and elevated oxygen radical production was also observed in vitro by altering the concentrations of glucose and fatty acids in the media or pharmacologic inhibition of glucose and fatty acid oxidation with 4-hydroxycyanocinnamic acid and etomoxir, respectively. 相似文献
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Involvement of rabphilin-3A-like (RPH3AL), or Noc2, the potential effector of Ras-associated binding proteins Rab3A and Rab27A in the regulation of exocytotic processes in the endocrine pancreas has been demonstrated in experimental models. Noc2 expression together with other regulatory molecules of the exocytotic machinery in human tissues, however, has not been studied. We evaluated immunohistochemical expression of the key molecules of the exocytotic machinery, Noc2, Rab3A, Rab27A, and RIM2, together with the characteristic islet cell hormones, insulin and glucagon in normal and endocrine tumor tissues of human pancreas. Normal pancreatic islets were stained for all of these proteins and showed strong cytoplasmic localization. A similar pattern of strong cytoplasmic expression of these proteins was observed in the majority of endocrine tumors. By contrast, the exocrine portions of normal appearing pancreas completely lacked Rab27A staining and showed decreased expression of the proteins, Noc2, Rab3A, and RIM2. The staining pattern of Noc2 and Rab27A was similar to the staining pattern of glucagon-producing cells within the islets. The concomitant expression of Noc2 with these molecules suggests that Noc2 may serve as an effector for Rab3A and Rab27A and that it is involved in the regulation of exocytosis of the endocrine pancreas in humans. 相似文献
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Molecular phylogeny of Neotropical bioluminescent beetles (Coleoptera: Elateroidea) in southern and central Brazil 下载免费PDF全文
Bioluminescence in beetles is found mainly in the Elateroidea superfamily (Elateridae, Lampyridae and Phengodidae). The Neotropical region accounts for the richest diversity of bioluminescent species in the world with about 500 described species, most occurring in the Amazon, Atlantic rainforest and Cerrado (savanna) ecosystems in Brazil. The origin and evolution of bioluminescence, as well as the taxonomic status of several Neotropical taxa in these families remains unclear. In order to contribute to a better understanding of the phylogeny and evolution of bioluminescent Elateroidea we sequenced and analyzed sequences of mitochondrial NADH2 and the nuclear 28S genes and of the cloned luciferase sequences of Brazilian species belonging to the following genera: (Lampyridae) Macrolampis, Photuris, Amydetes, Bicellonycha, Aspisoma, Lucidota, Cratomorphus; (Elateridae) Conoderus, Pyrophorus, Hapsodrilus, Pyrearinus, Fulgeochlizus; and (Phengodidae) Pseudophengodes, Phrixothrix, Euryopa and Brasilocerus. Our study supports a closer phylogenetic relationship between Elateridae and Phengodidae as other molecular studies, in contrast with previous morphologic and molecular studies that clustered Lampyridae/Phengodidae. Molecular data also supported division of the Phengodinae subfamily into the tribes Phengodini and Mastinocerini. The position of the genus Amydetes supports the status of the Amydetinae as a subfamily. The genus Euryopa is included in the Mastinocerini tribe within the Phengodinae/Phengodidae. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
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The ability to discriminate between galactose and N- acetylgalactosamine,
observed in some lectins, is crucial for their biological activity as well
as their usefulness as tools in biology and medicine. However, the
molecular basis of differential binding of lectins to these two sugars is
poorly understood. Peanut agglutinin (PNA) is one of the few
galactose-specific legume lectins which does not bind N-
acetylgalactosamine at all and is, therefore, ideal for the study of the
basis of specificity towards C-2 substituted derivatives of
galactopyranosides. Examination of the three-dimensional structure of PNA
in complex with lactose revealed the presence of both a longer loop and
bulkier residues in the region surrounding the C-2 hydroxyl of the
galactopyranoside ring, which can sterically prevent the accommodation of a
bulky substituent in this position. One such residue, is a glutamic acid at
position 129 which protrudes into the binding site and perhaps directly
obstructs any substitution at the C-2 position. Two mutants in bacterially
expressed PNA were therefore constructed. These were E129D and E129A, in
which Glu129 was replaced by Asp and Ala, respectively. The specificity of
the mutants for galactose, galactosamine, and N- acetylgalactosamine was
examined through observing the inhibition of hemagglutination and binding
of the lectin to immobilized asialofetuin. The results showed that the
affinity of E129A and E129D for C-2-substituted derivatives of the
galactose varies. The mutant E129D showed significant binding towards N-
acetylgalactosamine, suggesting that the residue Glu 129 is crucial in
imparting exclusive galactose-specificity upon PNA. This study not only
attempts to provide an explanation for the inability of PNA to accommodate
C-2-substituted derivatives at its primary subsite, but also seeks to
present a basis for engineering lectins with altered specificities.
相似文献
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Satish Kumar Rajasekhara Reddy Ravuri Padmaja Koneru BP Urade BN Sarkar A Chandrasekar VR Rao 《BMC evolutionary biology》2009,9(1):173-5
Background
An early dispersal of biologically and behaviorally modern humans from their African origins to Australia, by at least 45 thousand years via southern Asia has been suggested by studies based on morphology, archaeology and genetics. However, mtDNA lineages sampled so far from south Asia, eastern Asia and Australasia show non-overlapping distributions of haplogroups within pan Eurasian M and N macrohaplogroups. Likewise, support from the archaeology is still ambiguous. 相似文献7.
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