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91.
Peroxisome proliferator-activated receptor-gamma ligands inhibit adipocyte 11beta -hydroxysteroid dehydrogenase type 1 expression and activity 总被引:8,自引:0,他引:8
Berger J Tanen M Elbrecht A Hermanowski-Vosatka A Moller DE Wright SD Thieringer R 《The Journal of biological chemistry》2001,276(16):12629-12635
Peroxisome proliferator-activated receptor-gamma (PPARgamma) has been shown to play an important role in the regulation of expression of a subclass of adipocyte genes and to serve as the molecular target of the thiazolidinedione (TZD) and certain non-TZD antidiabetic agents. Hypercorticosteroidism leads to insulin resistance, a variety of metabolic dysfunctions typically seen in diabetes, and hypertrophy of visceral adipose tissue. In adipocytes, the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) converts inactive cortisone into the active glucocorticoid cortisol and thereby plays an important role in regulating the actions of corticosteroids in adipose tissue. Here, we show that both TZD and non-TZD PPARgamma agonists markedly reduced 11beta-HSD-1 gene expression in 3T3-L1 adipocytes. This diminution correlated with a significant decrease in the ability of the adipocytes to convert cortisone to cortisol. The half-maximal inhibition of 11beta-HSD-1 mRNA expression by the TZD, rosiglitazone, occurred at a concentration that was similar to its K(d) for binding PPARgamma and EC(50) for inducing adipocyte differentiation thereby indicating that this action was PPARgamma-dependent. The time required for the inhibitory action of the TZD was markedly greater for 11beta-HSD-1 gene expression than for leptin, suggesting that these genes may be down-regulated by different molecular mechanisms. Furthermore, whereas regulation of PPARgamma-inducible genes such as phosphoenolpyruvate carboxykinase was maintained when cellular protein synthesis was abrogated, PPARgamma agonist inhibition of 11beta-HSD-1 and leptin gene expression was ablated, thereby supporting the conclusion that PPARgamma affects the down-regulation of 11beta-HSD-1 indirectly. Finally, treatment of diabetic db/db mice with rosiglitazone inhibited expression of 11beta-HSD-1 in adipose tissue. This decrease in enzyme expression correlated with a significant decline in plasma corticosterone levels. In sum, these data indicate that some of the beneficial effects of PPARgamma antidiabetic agents may result, at least in part, from the down-regulation of 11beta-HSD-1 expression in adipose tissue. 相似文献
92.
93.
Birds differ considerably in the degree of male parental care,and it has been suggested that interspecific variation in extrapairpaternity is determined by the relative importance of benefitsto females from male parental care and good genes from extrapairsires. I estimated the relationship between extrapair paternityand the importance of male parental care for female reproductivesuccess mainly based on male removal studies, using a comparativeapproach. The reduction in female reproductive success causedby the absence of a male mate was positively correlated withthe male contribution to feeding offspring. The frequency ofextrapair paternity was negatively related to the reductionin female reproductive success caused by the absence of a mate.This was also the case when potentially confounding variablessuch as developmental mode of offspring and sexual dichromatismwere considered. A high frequency of extrapair paternity occursparticularly in bird species in which males play a minor rolein offspring provisioning and in which attractive males providerelatively little parental care. Bird species with frequentextrapair paternity thus appear to be those in which direct
fitness benefits from male care are small, females can readilycompensate for the absence of male care, and indirect fitnessbenefits from extrapair sires are important. 相似文献
94.
The Ca2+-dependent ATPase of sarcoplasmic reticulum after solubilization with deoxycholate and removal of lipid by gel chromatography exists as a mixture of monomer, dimer, and smaller amounts of higher molecular weight aggregates. The binding capcity of deoxycholate by monomeric and oligomeric forms of the ATPase is 0.3 g/g of protein at pH 8 and ionic strength 0.11. Examination in the analytical ultracentrifuge results in estimates of protein molecular weight of monomer of 115 000 +/- 7000 and of Stokes radius of 50-55 A. The results indicate an asymmetric shape of both delipidated monomer and dimer. Solubilization of ATPase vesicles by deoxycholate at high protein dilutions leads to almost instantaneous loss of ATPase activity. However, ATPase may be solubilized by deoxycholate in presence of phospholipid and sucrose in a temporarily active state. Inactivation appears to be accompanied by delipidation and conformational changes of the protein as evidenced by circular dichroism measurements. Sedimentation velocity examination of enzymatically active preparations of soluble ATPase in presence of phospholipid and sucrose strongly suggests that the major part of enzymatic activity is derived from a monomer with an asymmetric shape. The extent of formation of soluble oligomers by column chromatography was dependent on the exact conditions used for initial solubilization of ATPase. No evidence for differences among monomer and dimer fractions was obtained by isoelectric focusing and amino acid analysis. The results of these studies are compatible with electron-microscopic studies by other authors which suggest that the ATPase has an elongated shape with limited hydrophobic contact with the membrane lipid. A resemblance of delipidated oligomers with the form in which ATPase occurs in the membrane is conjectural at present. 相似文献
95.
Peter Moller Christian Schugardt Frank Kirschbaum 《Environmental Biology of Fishes》2004,70(2):175-184
Several sexually dimorphic characters of the anal-fin complex in the mormyrid fish, Mormyrus rume proboscirostris, assist during courtship when the male envelops the female's anal fin with its own to form a common spawning pouch (anal-fin
reflex). We found that developmental growth and seasonally cycling gonadal activity selectively affect their expression. The
structures defining the anal fin undergo a permanent sexually dimorphic transformation at a time when ripe spermatozoa first
appear in the testis of young males. However, the expression of a dorsally directed indentation of the posterior ventral body
wall, affecting the dorsal margin of the anal fin, appeared to be more plastic as it correlated with the gonadosomatic index,
that is, testis size. We surmised that this indentation is influenced by cyclic anabolic action on muscle involved with the
execution of the anal-fin reflex. 相似文献
96.
The Ca2+ -activated ATPase of sarcoplasmic reticulum can exist in true solution in the presence of some nonionic detergents, with retention of enzymatic activity for several days. The soluble active particles retain about 30 mol of phospholipid per mol of polypeptide chain even in the presence of a large excess of detergent, indicating the existence of relatively strong attractive forces between protein and lipid, as previous work from other laboratories has already suggested. Deoxycholate is much more effective than nonionic detergents in removing protein-bound lipid and, when used at solubilizing concentrations, completely delipidates and inactivates the ATPase. Preliminary molecular weight measurements indicate that the Ca2+ -ATPase exists as an oligomer in the native membrane: fully active enzyme in Tween 80 has a minimal protein molecular weight of about 400 000, corresponding to a trimer or tetramer of the ATPase polypeptide chain, and even the inactive enzyme in deoxycholate contains a substantial fraction of dimeric protein. 相似文献
97.
98.
Delaney JR Sutphin GL Dulken B Sim S Kim JR Robison B Schleit J Murakami CJ Carr D An EH Choi E Chou A Fletcher M Jelic M Liu B Lockshon D Moller RM Pak DN Peng Q Peng ZJ Pham KM Sage M Solanky A Steffen KK Tsuchiya M Tsuchiyama S Johnson S Raabe C Suh Y Zhou Z Liu X Kennedy BK Kaeberlein M 《Aging cell》2011,10(6):1089-1091
Activation of Sir2 orthologs is proposed to increase lifespan downstream of dietary restriction. Here, we describe an examination of the effect of 32 different lifespan-extending mutations and four methods of DR on replicative lifespan (RLS) in the short-lived sir2Δ yeast strain. In every case, deletion of SIR2 prevented RLS extension; however, RLS extension was restored when both SIR2 and FOB1 were deleted in several cases, demonstrating that SIR2 is not directly required for RLS extension. These findings indicate that suppression of the sir2Δ lifespan defect is a rare phenotype among longevity interventions and suggest that sir2Δ cells senesce rapidly by a mechanism distinct from that of wild-type cells. They also demonstrate that failure to observe lifespan extension in a short-lived background, such as cells or animals lacking sirtuins, should be interpreted with caution. 相似文献
99.
Sweiss NJ Zhang W Franek BS Kariuki SN Moller DR Patterson KC Bennett P Girijala LR Nair V Baughman RP Garcia JG Niewold TB 《PloS one》2011,6(12):e29126
Background
Both type I interferon (IFN), also known as IFN-α and tumor necrosis factor alpha (TNF-α) have been implicated in the pathogenesis of sarcoidosis. We investigated serum levels of these cytokines in a large multi-ancestral sarcoidosis population to determine correlations between cytokine levels and disease phenotypes.Methods
We studied serum samples from 98 patients with sarcoidosis, including 71 patients of African-American ancestry and 27 patients of European-American ancestry. Serum type I IFN was measured using a sensitive reporter cell assay and serum TNF-α was measured using a commercial ELISA kit. Clinical data including presence or absence of neurologic, cardiac, and severe pulmonary manifestations of sarcoidosis were abstracted from medical records. Twenty age-matched non-autoimmune controls were also studied from each ancestral background. Differences in cytokine levels between groups were analyzed with Mann-Whitney U test, and correlations were assessed using Spearman''s rho. Multivariate logistic regression models were used to detect associations between cytokines and clinical manifestations.Results
Significant differences in cytokine levels were observed between African- and European-American patients with sarcoidosis. In African-Americans, serum TNF-α levels were significantly higher relative to matched controls (P = 0.039), and patients with neurologic disease had significantly higher TNF-α than patients lacking this manifestation (P = 0.022). In European-Americans, serum type I IFN activity was higher in sarcoidosis cases as compared to matched controls, and patients with extra-pulmonary disease represented a high serum IFN subgroup (P = 0.0032). None of the associations observed were shared between the two ancestral groups.Conclusions
Our data indicate that significant associations between serum levels of TNF-α and type I IFN and clinical manifestations exist in a sarcoidosis cohort that differ significantly by self-reported ancestry. In each ancestral background, the cytokine elevated in patients with sarcoidosis was also associated with a particular disease phenotype. These findings may relate to ancestral differences in the molecular pathogenesis of this heterogeneous disease. 相似文献100.
H. Moller D. Fletcher P. N. Johnson Brian D. Bell D. Flack C. Bragg 《New Zealand journal of zoology.》2013,40(3):325-341
Abstract We estimated the change in abundance of sooty shearwater (titi, Puffinus griseus) at six Rakiura Titi Islands, New Zealand, by comparing historical and recent surveys of the density of entrances to breeding burrows. We found evidence that entrance density between 1994 and 2006 was lower than it was between 1961 and 1976. Our overall estimate of the annual rate of change in burrow entrance density is ‐1.0% (95% CI ‐2.3 to ‐ 0.1%). Declines have been slower on four islands where Rakiura Maori maintain a traditional harvest of sooty shearwater chicks ("muttonbirding") compared with three unharvested islands. Density‐dependent population processes may explain this difference: rates of decline have been faster in areas of relatively high initial entrance density, and historically the harvested islands have had lower initial density. There was a strong, apparently linear, relationship between entrance density and chick density on breeding colonies, so changes in entrance density probably do indicate a real population decline. The western side of Taukihepa, the largestof the Titi Islands, first became accessible for muttonbirding with the advent of helicopters in the 1970s, but it is unknown whether this has caused an increase in the number of sooty shearwaters harvested by Rakiura Maori. 相似文献