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131.
Yaoqing Wang Xiao Zhang Haoya Yao Xiaocui Chen Lin Shang Ping Li Xiaojuan Cui Jia Zeng 《The Journal of biological chemistry》2022,298(3)
Diabetes normally causes lipid accumulation and oxidative stress in the kidneys, which plays a critical role in the onset of diabetic nephropathy; however, the mechanism by which dysregulated fatty acid metabolism increases lipid and reactive oxygen species (ROS) formation in the diabetic kidney is not clear. As succinate is remarkably increased in the diabetic kidney, and accumulation of succinate suppresses mitochondrial fatty acid oxidation and increases ROS formation, we hypothesized that succinate might play a role in inducing lipid and ROS accumulation in the diabetic kidney. Here we demonstrate a novel mechanism by which diabetes induces lipid and ROS accumulation in the kidney of diabetic animals. We show that enhanced oxidation of dicarboxylic acids by peroxisomes leads to lipid and ROS accumulation in the kidney of diabetic mice via the metabolite succinate. Furthermore, specific suppression of peroxisomal β-oxidation improved diabetes-induced nephropathy by reducing succinate generation and attenuating lipid and ROS accumulation in the kidneys of the diabetic mice. We suggest that peroxisome-generated succinate acts as a pathological molecule inducing lipid and ROS accumulation in kidney, and that specifically targeting peroxisomal β-oxidation might be an effective strategy in treating diabetic nephropathy and related metabolic disorders. 相似文献
132.
Zirui Liu Yiquan Li Yilong Zhu Nan Li Wenjie Li Chao Shang Gaojie Song Shanzhi Li Jianan Cong Tingyu Li Zhiru Xiu Jing Lu Chenchen Ge Xia Yang Yaru Li Lili Sun Xiao Li Ningyi Jin 《International journal of biological sciences》2022,18(2):717
Apoptin is a small molecular weight protein encoded by the VP3 gene of chicken anemia virus (CAV). It can induce apoptosis of tumor cells and play anti-tumorigenic functions. In this study, we identified a time-dependent inhibitory role of apoptin on the viability of HCT116 cells. We also demonstrated that apoptin induces pyroptosis through cleaved caspase 3, and with a concomitant cleavage of gasdermin E (GSDME) rather than GSDMD. GSDME knockdown switched the apoptin-induced cell death from pyroptosis to apoptosis in vitro. Furthermore, we demonstrated that the effect of apoptin on GSDME-dependent pyroptosis could be mitigated by caspase-3 and caspase-9 siRNA knockdown. Additionally, apoptin enhanced the intracellular reactive oxygen species (ROS), causing aggregation of the mitochondrial membrane protein Tom20. Moreover, bax and cytochrome c were released to the activating caspase-9, eventually triggering pyroptosis. Therefore, GSDME mediates the apoptin-induced pyroptosis through the mitochondrial apoptotic pathway. Finally, using nude mice xenografted with HCT116 cells, we found that apoptin induces pyroptosis and significantly inhibits tumor growth. Based on this mechanism, apoptin may provide a new strategy for colorectal cancer therapy. 相似文献
133.
Shang M Koshikawa N Schenk S Quaranta V 《The Journal of biological chemistry》2001,276(35):33045-33053
Laminins are a family of extracellular matrix glycoproteins involved in cell adhesion and migration. A major obstacle to understanding their structure-function relationships is the lack of small laminin domains capable of replicating integrin-binding, cell-adhesive, and migratory functions of the intact molecule. Here, we show that the recombinant LG3 (rLG3) module (26 kDa) of laminin-5 (Ln-5) alpha(3) chain replicated key Ln-5 activities. rLG3 but not rLG1 or rLG2 supported cell adhesion and migration of at least two distinct cell lines, in an integrin alpha(3)beta(1)-dependent manner. Cell adhesion to rLG3 was regulated by divalent cations and accompanied by cell spreading and tyrosine phosphorylation of FAK focal adhesion kinase. The integrin binding activity of rLG3 was confirmed by rLG3 affinity chromatography of detergent cell lysates, which resulted in specific purification of integrin alpha(3)beta(1). To our knowledge, this is the first report directly demonstrating that a recombinant laminin LG module is an active domain capable of supporting integrin-dependent cell adhesion and migration. 相似文献
134.
Chen TY Shang HF Chen TL Lin CP Hui CF Hwang J 《Applied microbiology and biotechnology》1999,52(4):524-533
We have constructed a chimeric protein composed of the receptor binding and membrane translocation domains of Pseudomonas exotoxin A (PE) with the outer membrane proteins I and F, together designated as PEIF. The potential of PEIF as a vaccine
against Pseudomonas infection was evaluated in BALB/c mice and New Zealand white rabbits. We examined titers of anti-PE and anti-OprF antibodies,
and the ability both to neutralize PE cytotoxicity and to increase opsonophagocytic uptake of Pseudomonas aeruginosa strain PAO1, serogroups 2 and 6. The results showed that PEIF can induce antibodies not only to neutralize the PE cytotoxicity
but also to promote the uptake of various strains of P. aeruginosa by murine peritoneal macrophages. In a burned mouse model, PEIF afforded significant protection against infection by the
homologous P. aeruginosa strain PAO1, heterologous serogroup 2, and the PE hyperproducing strain PA103. These observations thus indicate that PEIF
may be used as a novel vaccine against P. aeruginosa infection.
Received: 10 March 1999 / Received revision: 21 April 1999 / Accepted: 16 May 1999 相似文献
135.
Behavior of Pythium torulosum Zoospores During Their Interaction with Tobacco Roots and Bacillus cereus 总被引:1,自引:0,他引:1
Bacillus cereus UW85 suppresses seedling damping-off diseases caused by Oomycetes and produces antibiotics that inhibit development of Oomycetes
in culture. The goal of this study was to determine how UW85 and its antibiotics affected the behavior of an Oomycete, Pythium torulosum, in its interaction with plant roots. We studied tobacco seedlings inoculated with zoospores of P. torulosum and UW85 culture, culture filtrate, washed cells, antibiotics (zwittermicin A or kanosamine), purified from cultures of UW85,
and UW030, a mutant of UW85 that does not suppress disease and does not produce the antibiotics. Microscopic observation revealed
that all of the treatments inhibited zoospore activity around roots and encystment on roots. Treatment with UW85 culture,
culture filtrate, zwittermicin A, or kanosamine delayed cyst germination and the elongation rate of germ tubes, whereas treatment
with UW030 or washed UW85 cells did not. In an in vitro seedling bioassay of disease suppression, the antibiotics, zwittermicin
A and kanosamine, suppressed disease singly or together, although UW85 culture suppressed disease more effectively than did
the antibiotics. The results show that B. cereus cultures affect zoospore behavior in the presence of roots, and B. cereus-produced antibiotics, zwittermicin A and kanosamine, contribute to disease suppression and inhibition of germ tube elongation
in the presence of the plant root.
Received: 9 September 1998 / Accepted: 13 October 1998 相似文献
136.
家族性高胆固醇血症患者低密度脂蛋白受体基因新突变位点的鉴定 总被引:4,自引:0,他引:4
Liu YR Tao QM Chen JZ Tao M Guo XG Shang YP Zhu JH Zhang FR Zheng LR Wang XX 《生理学报》2004,56(5):566-572
家族性高胆固醇血症(hypercholesterolemia familial,FH)是由于低密度脂蛋白受体(low density lipoprotein receptor,LDLR)基因突变导致的常染色体显性遗传性疾病,临床上表现为多发黄色瘤、高水平血浆LDL、早发性冠心病及有阳性家族史。本研究通过临床症状结合血脂测定诊断出一个FH家系,其纯合子FH患者的血浆总胆固醇水平高达19.05mmol/L,LDL达17.06mmol/L,并有黄色瘤;而杂合子FH患者的血浆总胆固醇水平为7.96mmol/L,LDL为5.55mmol/L,并有心绞痛症状和黄色瘤。我们对该FH家系患者LDLR基因的PCR扩增DNA片段进行测序,发现纯合子FH患者LDLR基因Exon4区域内发生了GAG683GCG突变,即编码LDLR第683位的谷氨酸被丙氨酸替换,而杂合子FH患者该位点呈现杂合突变。此基因型与临床诊断遗传谱完全一致。同时,利用获得Epstein-Barr(EB)病毒转化型人永生淋巴细胞株(EBV-Ls)与荧光探针DiI标记的LDL结合反应,再通过流式细胞仪检测结果显示,具有功能性LDLR的EBV-Ls细胞比例,在纯合子FH患者(7.02%)和杂合子FH患者(62.64%)均比健康对照者(84.69%)低,纯合子FH患者LDLR活性仅为健康对照者的8.29%、而杂合子FH患者LDLR活性约为健康对照者的73.96%,前者呈现非常显著的降低。这些EBV-Ls细胞LDLR的功能变化分析,有力地支持了该FH家系的临床诊断和DNA测序结果。经查阅最新的UMD-LDLR完全版证实,本研究发现鉴定的GAG683GCG突变是人LDLR基因的新突变位点。 相似文献
137.
Engineering of enhanced glycine betaine synthesis improves drought tolerance in maize 总被引:4,自引:0,他引:4
Glycine betaine plays an important role in some plants, including maize, in conditions of abiotic stress, but different maize varieties vary in their capacity to accumulate glycine betaine. An elite maize inbred line DH4866 was transformed with the betA gene from Escherichia coli encoding choline dehydrogenase (EC 1.1.99.1), a key enzyme in the biosynthesis of glycine betaine from choline. The transgenic maize plants accumulated higher levels of glycine betaine and were more tolerant to drought stress than wild-type plants (non-transgenic) at germination and the young seedling stage. Most importantly, the grain yield of transgenic plants was significantly higher than that of wild-type plants after drought treatment. The enhanced glycine betaine accumulation in transgenic maize provides greater protection of the integrity of the cell membrane and greater activity of enzymes compared with wild-type plants in conditions of drought stress. 相似文献
138.
Anti-IL-13 monoclonal antibody inhibits airway hyperresponsiveness, inflammation and airway remodeling 总被引:8,自引:0,他引:8
Yang G Volk A Petley T Emmell E Giles-Komar J Shang X Li J Das AM Shealy D Griswold DE Li L 《Cytokine》2004,28(6):224-232
Asthma is a chronic inflammatory disease characterized by reversible bronchial constriction, pulmonary inflammation and airway remodeling. Current standard therapies for asthma provide symptomatic control but fail to target the underlying disease pathology. Furthermore, no therapeutic agent is effective in preventing airway remodeling. Interleukin 13 (IL-13) is a pleiotropic cytokine produced mainly by T cells. A substantial amount of evidence suggests that IL-13 plays a critical role in the pathogenesis of asthma. Therefore, a neutralizing anti-IL-13 monoclonal antibody could provide therapeutic benefits to asthmatic patients. To test the concept we have generated a neutralizing rat anti-mouse IL-13 monoclonal antibody, and evaluated its effects in a chronic mouse model of asthma. Chronic asthma-like response was induced in ovalbumin (OVA) sensitized mice by repeated intranasal OVA challenges. After weeks of challenge, mice developed airway hyperresponsiveness (AHR) to methacholine stimulation, severe airway inflammation, hyper mucus production, and subepithelial fibrosis. When given at the time of each intranasal OVA challenge, anti-IL-13 antibody significantly suppressed AHR, eosinophil infiltration, proinflammatory cytokine/chemokine production, serum IgE, and most interestingly, airway remodeling. Taken together, these results strongly suggest that a neutralizing anti-human IL-13 monoclonal antibody could be an effective therapeutic agent for asthma. 相似文献
139.
140.