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21.
Bingqing Xia Xurui Shen Yang He Xiaoyan Pan Feng-Liang Liu Yi Wang Feipu Yang Sui Fang Yan Wu Zilei Duan Xiaoli Zuo Zhuqing Xie Xiangrui Jiang Ling Xu Hao Chi Shuangqu Li Qian Meng Hu Zhou Yubo Zhou Xi Cheng Xiaoming Xin Lin Jin Hai-Lin Zhang Dan-Dan Yu Ming-Hua Li Xiao-Li Feng Jiekai Chen Hualiang Jiang Gengfu Xiao Yong-Tang Zheng Lei-Ke Zhang Jingshan Shen Jia Li Zhaobing Gao 《Cell research》2021,31(8):847
Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that the SARS-CoV-2 envelope (2-E) protein alone is able to cause acute respiratory distress syndrome (ARDS)-like damages in vitro and in vivo. 2-E proteins were found to form a type of pH-sensitive cation channels in bilayer lipid membranes. As observed in SARS-CoV-2-infected cells, heterologous expression of 2-E channels induced rapid cell death in various susceptible cell types and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damages in lung and spleen. A dominant negative mutation lowering 2-E channel activity attenuated cell death and SARS-CoV-2 production. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent cell protective activity in vitro and these activities were positively correlated with inhibition of 2-E channel. Importantly, prophylactic and therapeutic administration of the channel inhibitor effectively reduced both the viral load and secretion of inflammation cytokines in lungs of SARS-CoV-2-infected transgenic mice expressing human angiotensin-converting enzyme 2 (hACE-2). Our study supports that 2-E is a promising drug target against SARS-CoV-2.Subject terms: Cell death, Molecular biology 相似文献
22.
Hanhan Liu Qiangqiang Jia Gianluca Tettamanti Sheng Li 《Insect biochemistry and molecular biology》2013,43(11):1068-1078
In the fruitfly, Drosophila melanogaster, autophagy and caspase activity function in parallel in the salivary gland during metamorphosis and in a common regulatory hierarchy during oogenesis. Both autophagy and caspase activity progressively increase in the remodeling fat body, and they are induced by a pulse of the molting hormone (20-hydroxyecdysone, 20E) during the larval-prepupal transition. Inhibition of autophagy and/or caspase activity in the remodeling fat body results in 25–40% pupal lethality, depending on the genotypes. Interestingly, a balancing crosstalk occurs between autophagy and caspase activity in this tissue: the inhibition of autophagy induces caspase activity and the inhibition of caspases induces autophagy. The Drosophila remodeling fat body provides an in vivo model for understanding the molecular mechanism of the balancing crosstalk between autophagy and caspase activity, which oppose with each other and are induced by the common stimulus 20E, and blockage of either path reinforces the other path. 相似文献
23.
24.
Three saponins from Oxytropis species. 总被引:2,自引:0,他引:2
Three flavonoids and three saponins have been isolated from Oxytropis species. Their structures were determined as isorhamnetin-3-O-beta-D-glucoside, rhamnetin-3-O-beta-D-galactoside, apigenin, 3-O-[alpha-L-rhamnopyranosyl (1----2)-beta-D-glucopyranosyl(1----4)-beta-D-glucuronopyranosyl]+ ++soyasapogenol B, 3-O-[beta-D-glucopyranosyl(1----2)-beta-D-glucuronopyranosyl] azukisapogenol and a new saponin 3-O-[beta-D-glucopyranosyl(1----2)-beta-D-glucopyranosyl]-25-O-alpha-L- rhamnopyranosyl-(20S,24S)-3 beta,16 beta, 20,24,25-pentahydroxy-9,19-cycloanostane. 相似文献
25.
Yu Bofan Liu Yang Liu Jia Guo Xiaorui Tang Zhonghua 《Journal of Plant Growth Regulation》2022,41(6):2093-2107
Journal of Plant Growth Regulation - In plants, apical hook opening is critical for the post-germination stage and subsequent photomorphogenesis, and this process is activated by a luminous... 相似文献
26.
Luqing Zhang Humphrey A. Mabwi Norberto J. Palange Ruirui Jia Jun Ma Fatoumata Binta Bah Rajiv Kumar Sah Dan Li Daji Wang Fatoumata Binta Maci Bah Jacques Togo Honghong Jin Luying Ban Xuechao Feng Yaowu Zheng 《PloS one》2015,10(11)
Disconnected (disco)-interacting protein 2 homolog A is a member of the DIP2 protein family encoded by Dip2a gene. Dip2a expression pattern has never been systematically studied. Functions of Dip2a in embryonic development and adult are not known. To investigate Dip2a gene expression and function in embryo and adult, a Dip2a-LacZ mouse model was generated by insertion of β-Gal cDNA after Dip2a promoter using CRISPR/Cas9 technology. Dip2a-LacZ mouse was designed to be a lacZ reporter mouse as well as a Dip2a knockout mouse. Heterozygous mice were used to study endogenous Dip2a expression and homozygotes to study DIP2A-associated structure and function. LacZ staining indicated that Dip2a is broadly expressed in neuronal, reproductive and vascular tissues, as well as in heart, kidney, liver and lung. Results demonstrate that Dip2a is expressed in ectoderm-derived tissues in developing embryos. Adult tissues showed rich staining in neurons, mesenchymal, endothelial, smooth muscle cells and cardiomyocytes by cell types. The expression pattern highly overlaps with FSTL1 and supports previous report that DIP2A to be potential receptor of FSTL1 and its protective roles of cardiomyocytes. Broad and intense embryonic and adult expression of Dip2a has implied their multiple structural and physiological roles. 相似文献
27.
28.
Erju Tang Xiaolin Shen Jia Wang Xinxiao Sun Qipeng Yuan 《Biotechnology and bioengineering》2020,117(4):1247-1252
myo-Inositol (MI) as a dietary supplement can provide various health benefits. One major challenge to its efficient biosynthesis is to achieve proper distribution of carbon flux between growth and production. Herein, this challenge was overcome by synergetic utilization of glucose and glycerol. Specifically, glycerol was catabolized to support cell growth while glucose was conserved as the building block for MI production. Growth and production were coupled via the phosphotransferase system, and both modules were optimized to achieve efficient production. First, the optimal enzyme combination was established for the production module. It was observed that enhancing the production module resulted in both increased MI production and better cell growth. In addition, glucose was shown to inhibit glycerol utilization via carbon catabolite repression and the inhibition was released by over-expressing glycerol kinase. Furthermore, the inducible promoter was replaced by strong constitutive promoters to avoid inducer use. With these efforts, the final strain produced MI with both high titer and yield. In fed-batch cultivation, 76 g/L of MI was produced, showing scale-up potential. This study provides a promising strategy to achieve rational distribution of carbon flux. 相似文献
29.
Michael A Weiss Satoe H Nakagawa Wenhua Jia Bin Xu Qing-xin Hua Ying-Chi Chu Run-ying Wang Panayotis G Katsoyannis 《Biochemistry》2002,41(3):809-819
Insulin provides a model of induced fit in macromolecular recognition: the hormone's conserved core is proposed to contribute to a novel receptor-binding surface. The core's evolutionary invariance, unusual among globular proteins, presumably reflects intertwined constraints of structure and function. To probe the architectural basis of such invariance, we have investigated hydrophobic substitutions of a key internal side chain (Leu(A16)). Although the variants exhibit perturbed structure and stability, moderate receptor-binding activities are retained. These observations suggest that the A16 side chain provides an essential structural buttress but unlike neighboring core side chains, does not itself contact the receptor. Among invertebrate insulin-like proteins, Leu(A16) and other putative core residues are not conserved, suggesting that the vertebrate packing scheme is not a general requirement of an insulin-like fold. We propose that conservation of Leu(A16) among vertebrate insulins and insulin-like growth factors is a side consequence of induced fit: alternative packing schemes are disallowed by lack of surrounding covariation within the hormone's hidden receptor-binding surface. An analogy is suggested between Leu(A16) and the spandrels of San Marco, tapering triangular spaces at the intersection of the dome's arches. This celebrated metaphor of Gould and Lewontin emphasizes the role of interlocking constraints in the evolution of biological structures. 相似文献
30.
Jia Xu Xinyu Guan Xiaodong Jia Hongyan Li Ruibing Chen Yinying Lu 《Molecular & cellular proteomics : MCP》2022,21(8):100255
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide with limited therapeutic options. Comprehensive investigation of protein posttranslational modifications in HCC is still limited. Lysine acetylation is one of the most common types of posttranslational modification involved in many cellular processes and plays crucial roles in the regulation of cancer. In this study, we analyzed the proteome and K-acetylome in eight pairs of HCC tumors and normal adjacent tissues using a timsTOF Pro instrument. As a result, we identified 9219 K-acetylation sites in 2625 proteins, of which 1003 sites exhibited differential acetylation levels between tumors and normal adjacent tissues. Interestingly, many novel tumor-specific K-acetylation sites were characterized, for example, filamin A (K865), filamin B (K697), and cofilin (K19), suggesting altered activities of these cytoskeleton-modulating molecules, which may contribute to tumor metastasis. In addition, we observed an overall suppression of protein K-acetylation in HCC tumors, especially for enzymes from various metabolic pathways, for example, glycolysis, tricarboxylic acid cycle, and fatty acid metabolism. Moreover, the expression of deacetylase sirtuin 2 (SIRT2) was upregulated in HCC tumors, and its role of deacetylation in HCC cells was further explored by examining the impact of SIRT2 overexpression on the proteome and K-acetylome in Huh7 HCC cells. SIRT2 overexpression reduced K-acetylation of proteins involved in a wide range of cellular processes, including energy metabolism. Furthermore, cellular assays showed that overexpression of SIRT2 in HCC cells inhibited both glycolysis and oxidative phosphorylation. Taken together, our findings provide valuable information to better understand the roles of K-acetylation in HCC and to treat this disease by correcting the aberrant acetylation patterns. 相似文献