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排序方式: 共有8891条查询结果,搜索用时 15 毫秒
21.
Chathurika Henpita Rajesh Vyas Chastity L. Healy Tra L. Kieu Aditi U. Gurkar Matthew J. Yousefzadeh Yuxiang Cui Aiping Lu Luise A. Angelini Ryan D. O'Kelly Sara J. McGowan Sanjay Chandrasekhar Rebecca R. Vanderpool Danielle Hennessy-Wack Mark A. Ross Timothy N. Bachman Charles McTiernan Smitha P. S. Pillai Warren Ladiges Mitra Lavasani Johnny Huard Donna Beer-Stolz Claudette M. St. Croix Simon C. Watkins Paul D. Robbins Ana L. Mora Eric E. Kelley Yinsheng Wang Timothy D. O'Connell Laura J. Niedernhofer 《Aging cell》2023,22(4):e13782
Cardiomyopathy is a progressive disease of the myocardium leading to impaired contractility. Genotoxic cancer therapies are known to be potent drivers of cardiomyopathy, whereas causes of spontaneous disease remain unclear. To test the hypothesis that endogenous genotoxic stress contributes to cardiomyopathy, we deleted the DNA repair gene Ercc1 specifically in striated muscle using a floxed allele of Ercc1 and mice expressing Cre under control of the muscle-specific creatinine kinase (Ckmm) promoter or depleted systemically (Ercc1−/D mice). Ckmm-Cre+/−;Ercc1−/fl mice expired suddenly of heart disease by 7 months of age. As young adults, the hearts of Ckmm-Cre+/−;Ercc1−/fl mice were structurally and functionally normal, but by 6-months-of-age, there was significant ventricular dilation, wall thinning, interstitial fibrosis, and systolic dysfunction indicative of dilated cardiomyopathy. Cardiac tissue from the tissue-specific or systemic model showed increased apoptosis and cardiac myocytes from Ckmm-Cre+/-;Ercc1−/fl mice were hypersensitive to genotoxins, resulting in apoptosis. p53 levels and target gene expression, including several antioxidants, were increased in cardiac tissue from Ckmm-Cre+/−;Ercc1−/fl and Ercc1−/D mice. Despite this, cardiac tissue from older mutant mice showed evidence of increased oxidative stress. Genetic or pharmacologic inhibition of p53 attenuated apoptosis and improved disease markers. Similarly, overexpression of mitochondrial-targeted catalase improved disease markers. Together, these data support the conclusion that DNA damage produced endogenously can drive cardiac disease and does so mechanistically via chronic activation of p53 and increased oxidative stress, driving cardiac myocyte apoptosis, dilated cardiomyopathy, and sudden death. 相似文献
22.
Cui Zhu Duilio M. Potenza Yang Yang Guillaume Ajalbert Kirsten D. Mertz Stephan von Gunten Xiu-Fen Ming Zhihong Yang 《Aging cell》2023,22(4):e13790
Elevated arginases including type-I (Arg-I) and type-II isoenzyme (Arg-II) are reported to play a role in aging, age-associated organ inflammaging, and fibrosis. A role of arginase in pulmonary aging and underlying mechanisms are not explored. Our present study shows increased Arg-II levels in aging lung of female mice, which is detected in bronchial ciliated epithelium, club cells, alveolar type 2 (AT2) pneumocytes, and fibroblasts (but not vascular endothelial and smooth muscle cells). Similar cellular localization of Arg-II is also observed in human lung biopsies. The age-associated increase in lung fibrosis and inflammatory cytokines, including IL-1β and TGF-β1 that are highly expressed in bronchial epithelium, AT2 cells, and fibroblasts, are ameliorated in arg-ii deficient (arg-ii−/−) mice. The effects of arg-ii−/− on lung inflammaging are weaker in male as compared to female animals. Conditioned medium (CM) from human Arg-II-positive bronchial and alveolar epithelial cells, but not that from arg-ii−/− cells, activates fibroblasts to produce various cytokines including TGF-β1 and collagen, which is abolished by IL-1β receptor antagonist or TGF-β type I receptor blocker. Conversely, TGF-β1 or IL-1β also increases Arg-II expression. In the mouse models, we confirmed the age-associated increase in IL-1β and TGF-β1 in epithelial cells and activation of fibroblasts, which is inhibited in arg-ii−/− mice. Taken together, our study demonstrates a critical role of epithelial Arg-II in activation of pulmonary fibroblasts via paracrine release of IL-1β and TGF-β1, contributing to pulmonary inflammaging and fibrosis. The results provide a novel mechanistic insight in the role of Arg-II in pulmonary aging. 相似文献
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I型马立克氏病毒38kD磷蛋白与Ⅱ和Ⅲ型病毒间的交叉免疫反应 总被引:3,自引:0,他引:3
由致病性Ⅰ型马立克氏病病毒(MDV)特异性的单克隆抗体H_(19)制备亲和层析柱,从感染重组杆状病毒BP38Ⅱ的昆虫细胞系Sf9细胞中提纯MDV的pp38基因表达产物,以此免疫小鼠制备抗血清,测定其与不同型MDV毒株感染的鸡胚成纤维细胞免疫反应性,同时也用不同型MDV毒株(HVT,Z4)制备的抗血清和自然感染发病鸡血清分别与感染重组病毒的Sf9细胞进行免疫交叉反应.试验结果表明,完整的Ⅰ型MDV来源的pp38基因产物与所试Ⅱ型Z4株和Ⅲ型HVT Fc126毒株在抗原性上有显著交叉反应.这一结果表明,在Ⅱ型和Ⅲ型MDV毒株中可能存在着pp38的类似物. 相似文献
27.
The relationship between head pteridine fluorescence (HPF) levels and age in adult females and males of a common necrophagous fly, Chrysomya megacephala, and effects of temperature and fly sex on the relationship were studied by pteridine fluorescence spectrophotometry. Factors affecting HPF levels in flies were found to include fly age, temperature and fly sex, among which the fly age was the most dominant one. There were significant linear relationships between HPF levels and age both for female and male adult flies at five constant temperatures, i. e. 16°C, 20°C, 24°C, 28°C and 32°C. The relationship between mean rate of pteridine accumulation (FV or MV) and temperature (t) could be well described by a modified exponential equation of FV=0.01288 e(0.2241t‐3.127)+0.3649 (r2= 0.9987) for females and a linear regression equation of MV= 0.0574 t ‐ 0.3637 (r2= 0.9557) for males. Using the information from the experiments at five constant temperatures, three calculated methods as the candidates were developed for accurately determining the age of the fly by HPF levels at ambient temperature. The results revealed that these three methods were suitable for estimating the age only for male flies, but not for female flies. The smallest average error of the predicated age was 2.55 days for males. In addition, how to employ which of these three developed methods for determining ages of male flies in practical was also discussed. 相似文献
28.
迷宫漏斗蛛Agelena labyrinthica的染色体(蜘蛛目:漏斗蛛科) 总被引:2,自引:0,他引:2
报告迷宫漏斗蛛的染色体数目、形态结构和性染色体组成。结果表明,迷宫漏斗蛛体细胞染色体数目是:雄性2n=42,雌性2n=44,性别决定机制属X_1X_2O型。X染色体是全部染色体中最长的和最短的2个(对)。染色体似乎均为端或亚端着丝粒染色体,这由C-显带标本分析所证实,没有亚中着丝粒染色体的证据。C-带标本分析表明,常染色体中,各条染色体的C-带纹,其大小和染色深浅无明显差异,但X_2染色体上有明显宽的C-带纹。C-显带处理没有得到稳定的有重复性的带纹。 相似文献
29.
神经节苷脂GM_3对小鼠腹腔常驻巨噬细胞(R-M)和Ge-132体内激活的巨噬细胞(Ge-132-M)的磷脂代谢转换有显著的影响,当这两种M在体外用GM_3处理时,表现出[ ̄(32)P]Pi和[ ̄3H]肌醇参入PI降低,参入PIP、PIP_2增加;但在[ ̄(32)P]Pi和[ ̄3H]胆碱参入PC上,R-M与Ge-132-M不同,即GM_3促进同位素前体参入R-M的PC,抑制它们参入Ge-132-M的PC.以上结果表明GM3可能提高了PI或PIP的磷酸激酶的活性,致使[ ̄(32)P]PIP和[ ̄(32)P]PIP_2增多,[ ̄(32)P]PI减少.激活的M(Ge-132-M)本身PC代谢转换率较R-M高,当Ge-132-M再受GM_3刺激,PC代谢转换率降低,这提示GM_3对激活的M的PC代谢转换有调节作用. 相似文献
30.
Whole-cell patch clamp recordings were done on giant protoplasts of Escherichia coli. The pressure sensitivity of the protoplasts was studied. Two different unit conductance mechanosensitive channels, 1100 ± 25 pS and 350 ± 14 pS in 400 mm symmetric KCl solution, were observed upon either applying positive pressure to the interior of the cells or down shocking the cells osmotically. The 1100 pS conductance channel discriminated poorly among the monovalent ions tested and it was permeable to Ca2+ and glutamate?. Both of the two channels were sensitive to the osmotic gradient across the membrane; the unit conductances of the channels remained constant while the mean current of the cell was increased by increasing the osmotic gradient. Both of the channels were voltage sensitive. Voltage-ramp results showed that the pressure sensitivity of protoplasts was voltage dependent: there were more channels active upon depolarization than hyperpolarization. The mech anosensitive channels were reversibly blocked by gadolinium ion. Also they could reversibly be inhibited by protons. Mutations in two of the potassium efflux systems, KefB and KefC, did not affect the channel activity, while a null mutation in the gene for KefA changed the channel activity significantly. This indicates a potential modulation of these channels by KefA. 相似文献