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941.
Preferential apoptosis of HIV-1-specific CD4+ T cells 总被引:4,自引:0,他引:4
Yue FY Kovacs CM Dimayuga RC Gu XX Parks P Kaul R Ostrowski MA 《Journal of immunology (Baltimore, Md. : 1950)》2005,174(4):2196-2204
In contrast to other viral infections such as CMV, circulating frequencies of HIV-1-specific CD4+ T cells in peripheral blood are quantitatively diminished in the majority of HIV-1-infected individuals. One mechanism for this quantitative defect is preferential infection of HIV-1-specific CD4+ T cells, although <10% of HIV-1-specific CD4+ T cells are infected. Apoptosis has been proposed as an important contributor to the pathogenesis of CD4+ T cell depletion in HIV/AIDS. We show here that, within HIV-1-infected individuals, a greater proportion of ex vivo HIV-1-specific CD4+ T cells undergo apoptosis compared with CMV-specific CD4+ T cells (45 vs 7.4%, respectively, p < 0.05, in chronic progressors). The degree of apoptosis within HIV-1-specific CD4+ T cells correlates with viral load and disease progression, and highly active antiretroviral therapy abrogates these differences. The data support a mechanism for apoptosis in these cells similar to that found in activation-induced apoptosis through the TCR, resulting in oxygen-free radical production, mitochondrial damage, and caspase-9 activation. That HIV-1 proteins can also directly enhance activation-induced apoptosis supports a mechanism for a preferential induction of apoptosis of HIV-1-specific CD4+ T cells, which contributes to a loss of immunological control of HIV-1 replication. 相似文献
942.
Bi-directional regulation between tyrosine kinase Etk/BMX and tumor suppressor p53 in response to DNA damage 总被引:3,自引:0,他引:3
943.
Placental blood flow, nitric-oxide (NO) levels, and endothelial NO synthase (eNOS) expression increase during human and ovine pregnancy. Shear stress stimulates NO production and eNOS expression in ovine fetoplacental artery endothelial (OFPAE) cells. Because eNOS is the rate-limiting enzyme essential for NO synthesis, its activity and expression are both closely regulated. We investigated signaling mechanisms underlying pulsatile shear stress-induced increases in eNOS phosphorylation and protein expression by OFPAE cells. The OFPAE cells were cultured at 3 dynes/cm2 shear stress, then exposed to 15 dynes/cm2 shear stress. Western blot analysis for phosphorylated ERK1/2, Akt, p38 mitogen activated protein kinase (MAPK), and eNOS showed that shear stress rapidly increased phosphorylation of ERK1/2 and Akt but not of p38 MAPK. Phosphorylation of eNOS Ser1177 under shear stress was elevated by 20 min, a response that was blocked by the phosphatidyl inositol-3-kinase (PI-3K)-inhibitors wortmannin and LY294002 but not by the mitogen activated protein kinase kinase (MEK)-inhibitor UO126. Basic fibroblast growth factor (bFGF) enhanced eNOS protein levels in static culture via a MEK-mediated mechanism, but it could not further augment the elevated eNOS protein levels otherwise induced by the 15 dynes/cm2 shear stress. Blockade of either signaling pathway changed the shear stress-induced increase in eNOS protein levels. In conclusion, shear stress induced rapid eNOS phosphorylation on Ser1177 in OFPAE cells through a PI-3K-dependent pathway. The bFGF-induced rise in eNOS protein levels in static culture was much less than those observed under flow and was blocked by inhibition of MEK. Prolonged shear stress-stimulated increases in eNOS protein were not affected by inhibition of MEK- or PI-3K-mediated pathways. 相似文献
944.
DNA topoisomerase (topo) IIalpha, an essential enzyme for cell proliferation, is targeted to a proteasome-dependent degradation pathway when human tumor cells are glucose-starved. Here we show that the topo IIalpha destabilization depends on the newly identified domain, GRDD (glucose-regulated destruction domain), which was mapped to the N-terminal 70-170 amino acid sequence. Indeed, the deletion of GRDD conferred a stable feature on topo IIalpha, whereas the fusion of GRDD rendered green fluorescent protein unstable under glucose starvation conditions. Nuclear localization was a prerequisite for GRDD function, because the inhibition of nuclear translocation resulted in the suppression of GRDD-mediated topo IIalpha degradation. Further, GRDD was identified as an interactive domain for Jab1/CSN5, which promoted the degradation of topo IIalpha in a manner dependent on the MPN (Mpr1p/Prd1p N terminus) domain. Depleting Jab1/CSN5 by antisense oligonucleotide and treating cells with the CSN-associated kinase inhibitor, curcumin, inhibited topo IIalpha degradation induced by glucose starvation. These findings demonstrate that GRDD can act as a stress-activated degron for regulating topo IIalpha stability, possibly through interaction with the MPN domain of Jab1/CSN5. 相似文献
945.
Yun HS Jeong WI Do SH Jeong DH Jung YR Park JK Cho EM Jeong KS 《Biochemical and biophysical research communications》2004,320(3):852-859
The purpose of this study was to investigate the protective effect of bio-active ceramic water on rat liver. Male Wistar rats were divided into 4 groups of 15 animals each. Groups 1 and 2 were fed bio-active ceramic water and tap water for 4 months, respectively. Groups 3 and 4 were treated with the same condition for 12 months. The changes of protein expression of these four groups were investigated using two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Eleven proteins were significantly up-regulated in bio-active ceramic water treated rat liver including aldehyde dehydrogenase I and II, albumin, fructose-1,6-bisphosphatase, and superoxide dismutase I (SOD I). The most highly expressed protein, SOD I with up-regulated enzyme activity, was confirmed by immunoblots as a major antioxidant capable of detoxifying normally generated reactive oxygen species. These data suggest that modified protein expression of the liver contributes to enhance liver function. 相似文献
946.
Quantitative kinetic analysis of nucleolar breakdown and reassembly during mitosis in live human cells 总被引:12,自引:0,他引:12
Leung AK Gerlich D Miller G Lyon C Lam YW Lleres D Daigle N Zomerdijk J Ellenberg J Lamond AI 《The Journal of cell biology》2004,166(6):787-800
One of the great mysteries of the nucleolus surrounds its disappearance during mitosis and subsequent reassembly at late mitosis. Here, the relative dynamics of nucleolar disassembly and reformation were dissected using quantitative 4D microscopy with fluorescent protein-tagged proteins in human stable cell lines. The data provide a novel insight into the fates of the three distinct nucleolar subcompartments and their associated protein machineries in a single dividing cell. Before the onset of nuclear envelope (NE) breakdown, nucleolar disassembly started with the loss of RNA polymerase I subunits from the fibrillar centers. Dissociation of proteins from the other subcompartments occurred with faster kinetics but commenced later, coincident with the process of NE breakdown. The reformation pathway also follows a reproducible and defined temporal sequence but the order of reassembly is shown not to be dictated by the order in which individual nucleolar components reaccumulate within the nucleus after mitosis. 相似文献
947.
Targeted deletion of protein kinase C lambda reveals a distribution of functions between the two atypical protein kinase C isoforms 总被引:1,自引:0,他引:1
Soloff RS Katayama C Lin MY Feramisco JR Hedrick SM 《Journal of immunology (Baltimore, Md. : 1950)》2004,173(5):3250-3260
Protein kinase C lambda (PKClambda) is an atypical member of the PKC family of serine/threonine kinases with high similarity to the other atypical family member, PKCzeta. This similarity has made it difficult to determine specific roles for the individual atypical isoforms. Both PKClambda and PKCzeta have been implicated in the signal transduction, initiated by mediators of innate immunity, that culminates in the activation of MAPKs and NF-kappaB. In addition, work from invertebrates shows that atypical PKC molecules play a role in embryo development and cell polarity. To determine the unique functions of PKClambda, mice deficient for PKClambda were generated by gene targeting. The ablation of PKClambda results in abnormalities early in gestation with lethality occurring by embryonic day 9. The role of PKClambda in cytokine-mediated cellular activation was studied by making mouse chimeras from PKClambda-deficient embryonic stem cells and C57BL/6 or Rag2-deficient blastocysts. Cell lines derived from these chimeric animals were then used to dissect the role of PKClambda in cytokine responses. Although the mutant cells exhibited alterations in actin stress fibers and focal adhesions, no other phenotypic differences were noted. Contrary to experiments using dominant interfering forms of PKClambda, mutant cells responded normally to TNF, serum, epidermal growth factor, IL-1, and LPS. In addition, no abnormalities were found in T cell development or T cell activation. These data establish that, in vertebrates, the two disparate functions of atypical PKC molecules have been segregated such that PKCzeta mediates signal transduction of the innate immune system and PKClambda is essential for early embryogenesis. 相似文献
948.
In this paper, the global asymptotic behavior of a chemostat model with Beddington-DeAngelis functional response is studied. The conditions for the global asymptotical stability of the model with time delays are obtained via monotone dynamical systems. Our results demonstrate that those time delays affect the competitive outcome of the organisms. 相似文献
949.
Comparative studies on histological and ultra-structure of the pituitary of different ploidy level fishes 总被引:4,自引:3,他引:1
Yu Long Shaojun Liu Weiren Huang Jian Zhang Yuandong Sun Chun Zhang Song Chen Jinghui Liu Yun Liu 《中国科学:生命科学英文版》2006,49(5):446-453
The histological and ultra-structure of the pituitary in diploid red crucian carp(Carassius auratus red var.),triploid crucian carp and allotetraploid hybrids within and after the breeding season were comparatively studied.The result showed that there were six endocrine cell types in the pituitary of these three kinds of fishes,and there was an obvious difference in cell size among different ploidy level fishes.As for the same type of pituitary cells,the cell size was increased gradually with the in- creasing ploidy level.In the breeding season,the allotetraploid hybrids had higher proportion of go- nadotropin cells(GTH)than triploids,and the triploids had higher proportion of GTH than diploids.The results were related to the earlier sexual maturity of allotetraploid hybrids and sterility of triploid cru- cian carp.On the other hand,among the three kinds of fishes,the proportion of somatotropin(STH) cells in triploids crucian carp was the highest,whereas that in allotetraploid hybrids was the lowest. The results might be connected with the faster growth rate of triploids and slower growth rate of al- lotetraploid hybrids.In addition,in GTH cells of meso-adenohypophysis after the breeding season, there were many endocrine particles in triploids,while those endocrine particles were released from the cells in allotetraploids and diploids.This result showed that the sterility of triploid crucian carp might be related to the hormone which was not released from the GTH cells.In a word,the present study indicated that the differences in the structure of pituitary among different ploidy level fishes contributed to their difference in the growth rate and gonadal development. 相似文献
950.
Lee S Min HG Choi SH Kim YJ Oh SW Kim YJ Park Y Kim SS 《Obesity (Silver Spring, Md.)》2006,14(1):172-179
Objective: Obesity‐related metabolic diseases may influence prostatic hyperplasia. This study examined the impact of obesity on prostate volume in men without overt obesity‐related metabolic diseases. Research Methods and Procedures: We recruited 146 men over the age of 40 years who did not have overt obesity‐related diseases, such as diabetes, impaired fasting glucose, hypertension, or dyslipidemia. Transrectal ultrasonography was performed on all subjects. The subjects were divided into three groups according to their BMI: normal (18.5 to 22.9 kg/m2), overweight (23 to 24.9 kg/m2), and obese (≥25 kg/m2), and two groups according to their waist circumference: normal waist (≤90 cm) and central obesity (>90 cm). The classification of the subgroups was based on the Asia‐Pacific criteria of obesity. We compared the prostate volume among subgroups and assessed factors related to prostatic hyperplasia. Results: Mean prostate volume was 18.8 ± 5.0, 21.8 ± 7.2, and 21.8 ± 5.6 mL in the normal, overweight, and obese groups, respectively, and was 20.0 ± 5.9 and 23.7 ± 5.3 mL in the normal waist and central obesity group, respectively. Prostate volume was significantly greater in the obese group than in the normal group (P = 0.03) and in the central obesity group compared with the normal waist group (P = 0.002). Prostate volume was positively correlated with BMI and waist circumference after adjustment for age. After adjusting for confounding factors, central obesity was an independent factor affecting prostatic hyperplasia, which was defined as a prostate volume >20 mL (odds ratio = 3.37, p = 0.037). Relative to men with both low BMI (18.5 to 22.9 kg/m2) and normal waist circumference, those with high BMI (≥25 kg/m2) and central obesity were at significantly increased risk of prostatic hyperplasia (odds ratio = 4.88, p = 0.008). However, those with high BMI (≥25 kg/m2) and normal waist circumference were not at significantly increased risk. Discussion: Prostate volume was greater in the obese and central obesity groups than in the normal group after patients with overt obesity‐related metabolic diseases were excluded. Although both BMI and waist circumference were positively correlated with prostate volume, central obesity was the only independent factor affecting prostate hyperplasia. We suggest that central obesity is an important risk factor for prostatic hyperplasia. 相似文献