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排序方式: 共有533条查询结果,搜索用时 156 毫秒
31.
van der Veen RC Dietlin TA Hofman FM Pen L Segal BH Holland SM 《Journal of immunology (Baltimore, Md. : 1950)》2000,164(10):5177-5183
NO, which suppresses T cell proliferation, may be inactivated by superoxide (O2-) due to their strong mutual affinity. To examine this possibility, preactivated Th clones were cocultured with stimulated macrophages. PMA neutralized the inhibitory activity of NO, which was dependent on extracellular O2- production. In contrast, macrophages from p47phox -/- (pKO) mice, which lack functional NADPH oxidase, retained their NO-dependent inhibition of T cell proliferation upon stimulation with PMA, indicating that NADPH oxidase is the major source of NO-inactivating O2- in this system. To examine the NO-O2- interaction in vivo, the role of NADPH oxidase in experimental autoimmune encephalomyelitis was studied in pKO mice. No clinical or histological signs were observed in the pKO mice. Neither a bias in Th subsets nor a reduced intensity of T cell responses could account for the disease resistance. Although spleen cells from pKO mice proliferated poorly in response to the immunogen, inhibition of NO synthase uncovered a normal proliferative response. These results indicate that NO activity may play a critical role in T cell responses in pKO mice and that in normal spleens inhibition of T cell proliferation by NO may be prevented by simultaneous NADPH oxidase activity. 相似文献
32.
Energy metabolism in uncoupling protein 3 gene knockout mice 总被引:27,自引:0,他引:27
Vidal-Puig AJ Grujic D Zhang CY Hagen T Boss O Ido Y Szczepanik A Wade J Mootha V Cortright R Muoio DM Lowell BB 《The Journal of biological chemistry》2000,275(21):16258-16266
Uncoupling protein 3 (UCP3) is a member of the mitochondrial anion carrier superfamily. Based upon its high homology with UCP1 and its restricted tissue distribution to skeletal muscle and brown adipose tissue, UCP3 has been suggested to play important roles in regulating energy expenditure, body weight, and thermoregulation. Other postulated roles for UCP3 include regulation of fatty acid metabolism, adaptive responses to acute exercise and starvation, and prevention of reactive oxygen species (ROS) formation. To address these questions, we have generated mice lacking UCP3 (UCP3 knockout (KO) mice). Here, we provide evidence that skeletal muscle mitochondria lacking UCP3 are more coupled (i.e. increased state 3/state 4 ratio), indicating that UCP3 has uncoupling activity. In addition, production of ROS is increased in mitochondria lacking UCP3. This study demonstrates that UCP3 has uncoupling activity and that its absence may lead to increased production of ROS. Despite these effects on mitochondrial function, UCP3 does not seem to be required for body weight regulation, exercise tolerance, fatty acid oxidation, or cold-induced thermogenesis. The absence of such phenotypes in UCP3 KO mice could not be attributed to up-regulation of other UCP mRNAs. However, alternative compensatory mechanisms cannot be excluded. The consequence of increased mitochondrial coupling in UCP3 KO mice on metabolism and the possible role of yet unidentified compensatory mechanisms, remains to be determined. 相似文献
33.
Shimizu S Gabazza EC Hayashi T Ido M Adachi Y Suzuki K 《American journal of physiology. Lung cellular and molecular physiology》2000,279(3):L503-L510
Several growth factors, including platelet-derived growth factor (PDGF), have been implicated in the mechanism of lung and airway remodeling. In the present study, we evaluated whether thrombin may promote lung and airway remodeling by increasing PDGF production from lung and airway epithelial cells. Conditioned medium (CM) was prepared by treating epithelial cells with increasing concentrations of thrombin; before use in the assays, CM was treated with hirudin until complete inhibition of thrombin activity. CM from epithelial cells stimulated the proliferation of lung fibroblasts and bronchial smooth muscle cells. Anti-PDGF antibody significantly inhibited this CM proliferative activity, implicating PDGF in this effect. Enzyme immunoassay and RT-PCR demonstrated that thrombin induced the secretion and expression of PDGF from bronchial and alveolar epithelial cells. RT-PCR showed that epithelial cells express the thrombin receptors protease-activated receptor (PAR)-1, PAR-3, and PAR-4. The PAR-1 agonist peptide was also found to induce PDGF secretion from epithelial cells, suggesting that the cellular effect of thrombin occurs via a PAR-1-mediated mechanism. Overall, this study showed for the first time that thrombin may play an important role in the process of lung and airway remodeling by stimulating the expression of PDGF via its cellular receptor, PAR-1. 相似文献
34.
Edmundo Chávez Antonio Penña Cecilia Zazueta Jorge Ramírez Noemí García Raymundo Carrillo 《Journal of bioenergetics and biomembranes》2000,32(2):193-198
Mitochondrial permeability transition occurs through a Ca2+-dependent opening of atransmembrane pore, whose identity has been attributed to that of the adenine nucleotide translocase(ANT). In this work, we induced permeability transition by adding 0.5 M carboxyatractyloside.The process was evaluated analyzing Ca2+ efflux, a drop in transmembrane electric gradient,and swelling. We found that the amphiphyllic cations octylguanidine and octylamine, at theconcentration of 100 M, inhibited, almost completely, nonspecific membrane permeability.Hexylguanidine, hexylamine, as well as guanidine chloride and hydroxylamine failed to doso. The inhibition was reversed after the addition of 40 mM Li+, Na+ K+,Rb+, or Cs+; K+ wasthe most effective. We propose that the positive charge of the amines interact with negativecharges of membrane proteins, more likely the ADP/ATP carrier, while the alkyl chain penetratesinto the hydrophobic milieu of the inner membrane, fixing the reagent. 相似文献
35.
Stability of pre- and post-fire spatial structure of pine trees in Aleppo pine forest 总被引:2,自引:0,他引:2
The study reported here describes for the first time the similarity between pre- and post-fire spatial patterns of the trees in a Mediterranean pine forest demonstrating that the pre-fire ancestor microsite is occupied also by the next generation. Although Aleppo pine Pinus halepensis Mill, is an obligatory post-fire seeder, it is adapted to regenerate in its pre-fire growing microsite. thus keeping suitable growing sites from generation to generation. We studied the effect of the dead burned adult pines on the density and size of their recruited saplings 2, 5, 11 and 20 yr after fire. A comparison of pine sapling density and size was made between the "near" zone (under the former effect of the burned canopy) and the'far'zone (beyond the former effect of the burned canopy).
In the site 2 yr after fire, seedling density was 56% higher in the "far" zone than in the'near'zone, but seedling .size was similar. However in the site 20 yr after fire, densities were similar in both zones, but the size was bigger by 89% in the "near" zone. Thus, population recruitment after fire seems to peak near the burned pine trees rather than at u distance from them, in contrast to Janzen's original'distance hypothesis' model suggested for undisturbed rainforest. Mere we present a new hypothetical model for the spatial pattern of post-fire regeneration of obligate seeder tree species forming open forests. It is proposed that in such trees the microsites which were kept by the burned adult trees, which are killed by the fire, are also the favorable regeneration microsite for the post-fire generation. 相似文献
In the site 2 yr after fire, seedling density was 56% higher in the "far" zone than in the'near'zone, but seedling .size was similar. However in the site 20 yr after fire, densities were similar in both zones, but the size was bigger by 89% in the "near" zone. Thus, population recruitment after fire seems to peak near the burned pine trees rather than at u distance from them, in contrast to Janzen's original'distance hypothesis' model suggested for undisturbed rainforest. Mere we present a new hypothetical model for the spatial pattern of post-fire regeneration of obligate seeder tree species forming open forests. It is proposed that in such trees the microsites which were kept by the burned adult trees, which are killed by the fire, are also the favorable regeneration microsite for the post-fire generation. 相似文献
36.
Yasuo Ido Albert Duranton Fan Lan Karen A. Weikel Lionel Breton Neil B. Ruderman 《PloS one》2015,10(2)
The aging process is perceived as resulting from a combination of intrinsic factors such as changes in intracellular signaling and extrinsic factors, most notably environmental stressors. In skin, the relationship between intrinsic changes and keratinocyte function is not clearly understood. Previously, we found that increasing the activity of AMP-activated protein kinase (AMPK) suppressed senescence in hydrogen peroxide (H2O2)-treated human primary keratinocytes, a model of oxidative stress-induced cellular aging. Using this model in the present study, we observed that resveratrol, an agent that increases the activities of both AMPK and sirtuins, ameliorated two age-associated phenotypes: cellular senescence and proliferative dysfunction. In addition, we found that treatment of keratinocytes with Ex527, a specific inhibitor of sirtuin 1 (SIRT1), attenuated the ability of resveratrol to suppress senescence. In keeping with the latter observation, we noted that compared to non-senescent keratinocytes, senescent cells lacked SIRT1. In addition to these effects on H2O2-induced senescence, resveratrol also prevented the H2O2-induced decrease in proliferation (as indicated by 3H-thymidine incorporation) in the presence of insulin. This effect was abrogated by inhibition of AMPK but not SIRT1. Compared to endothelium, we found that human keratinocytes expressed relatively high levels of Forkhead box O3 (FOXO3), a downstream target of both AMPK and SIRT1. Treatment of keratinocytes with resveratrol transactivated FOXO3 and increased the expression of its target genes including catalase. Resveratrol’s effects on both senescence and proliferation disappeared when FOXO3 was knocked down. Finally, we performed an exploratory study which showed that skin from humans over 50 years old had lower AMPK activity than skin from individuals under age 20. Collectively, these findings suggest that the effects of resveratrol on keratinocyte senescence and proliferation are regulated by the AMPK-FOXO3 pathway and in some situations, but not all, by SIRT1. 相似文献
37.
Jin Ming Di Jun Pang Qi Peng Sun Yan Zhang You Qiang Fang Xiao Pen Liu Jian Hua Zhou Xing Xing Ruan Xin Gao 《Molecular biology reports》2010,37(4):1849-1855
CpG-oligonucleotides (CpG-ODNs), mimicking bacterial DNA, have recently been shown to stimulate prostate cancer invasion in
vitro via Toll-like receptor 9 (TLR9). Since cyclooxygenase 2 (COX-2), frequently overexpressed in multiple tumor types including
prostate cancer, is a causal factor for tumor development, invasion and metastasis, an interesting question is raised whether
TLR9 regulates COX-2 expression in prostate cancer cells. To address this question, herein we examined COX-2 expression in
PC-3 cells stimulated with different doses and time courses of CpG-ODNs. The regulatory role of NF-κB in TLR9-mediated COX-2
expression was also investigated. CpG-ODN was found to up-regulate the expression of COX-2 in PC-3 cells in a dose- and time-dependent
manner, but have little impact on COX-1 expression. Moreover, CpG-ODN also promoted nuclear translocation and activation of
NF-κB, which appeared to be required for COX-2 induction by CpG-ODN. Overall, TLR9 up-regulates COX-2 expression in prostate
cancer cells, at least partially through the activation of NF-κB, which may be implicated in tumor invasion and metastasis. 相似文献
38.
39.
The reproductive biology, growth and diet of Galaxiella munda McDowall in a south-western Australian river are described. Monthly trends in gonadosomatic indices, stages in ovarian development and the size and maturity of oocytes show that spawning extended from July to October and peaked in late August to early September. Histology of ovaries indicated that G. munda produced clutches of eggs which it released at intervals. Data on length-frequencies, otoliths and gonads demonstrate that G. munda typically died in the few months after spawning. By age I, the females and males of G. munda had reached 47 mm (≡ 0.54 g) and 43 mm (≡ 0.42 g), respectively. The respective von Bertalanffy growth curve parameters for L., K and to were 48.6 mm, 3.702 and -0.0014 for females and 44.3 mm, 4.217 and -0.0012 for males. Galaxiella munda fed predominantly on terrestrial fauna on the water surface, cladocerans and copepods in the water column, and dipteran larvae in the benthos. Comparisons are made between the above aspects of the biology of G. munda and those recorded for three other locally endemic species ( Galaxias occidentalis Ogilby, Bostockia porosa Castelnau and Edelia vittata Castelnau) and wherever possible with other Galaxiella species. Such comparisons have emphasized the relationship between size and age at first maturity and spawning mode. 相似文献
40.
In most species, some individuals delay reproduction or occupy inferior breeding positions. The queue hypothesis tries to explain both patterns by proposing that individuals strategically delay breeding (queue) to acquire better breeding or social positions. In 1995, Ens, Weissing, and Drent addressed evolutionarily stable queuing strategies in situations with habitat heterogeneity. However, their model did not consider the non-mutually exclusive individual quality hypothesis, which suggests that some individuals delay breeding or occupy inferior breeding positions because they are poor competitors. Here we extend their model with individual differences in competitive abilities, which are probably plentiful in nature. We show that including even the smallest competitive asymmetries will result in individuals using queuing strategies completely different from those in models that assume equal competitors. Subsequently, we investigate how well our models can explain settlement patterns in the wild, using a long-term study on oystercatchers. This long-lived shorebird exhibits strong variation in age of first reproduction and territory quality. We show that only models that include competitive asymmetries can explain why oystercatchers' settlement patterns depend on natal origin. We conclude that predictions from queuing models are very sensitive to assumptions about competitive asymmetries, while detecting such differences in the wild is often problematic. 相似文献