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Live-Cell Imaging of Dual-Labeled Golgi Stacks in Tobacco BY-2 Cells Reveals Similar Behaviors for Different Cisternae during Movement and brefeldin a Treatment

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Molecular Plant 2011年第5期4卷 896-908页

作者： Stephanie L. Madison Andreas Nebenfuhr Department of Biochemistry and Cellular and Molecular Biology University of Tennessee Knoxville TN 37996-0840 USA

In plant cells, the Golgi apparatus consists of numerous stacks that, in turn, are composed of several flattened cisternae with a clear cis-to-trans polarity. During normal functioning within living cells, this unusual organelle displays a wide range of dynamic behaviors such as whole stack motility, constant membrane flux through the cisternae, and Golgi enzyme recycling through the ER. In order to further investigate various aspects of Golgi stack dynamics and integrity, we co-expressed pairs of established Golgi markers in tobacco BY-2 cells to distinguish sub-compartments of the Golgi during monensin treatments, movement, and brefeldin a （BFA）-induced disassembly. A combination of cis and trans markers revealed that Golgi stacks remain intact as they move through the cytoplasm. The Golgi stack orientation during these movements showed a slight preference for the cis side moving ahead, but trans cisternae were also found at the leading edge. During BFA treatments, the different sub-compartments of about half of the observed stacks fused with the ER sequentially; however, no consistent order could be detected. In contrast, the ionophore monensin resulted in swelling of trans cisternae while medial and particularly cis cisternae were mostly unaffected. Our results thus demonstrate a re- markable equivalence of the different cisternae with respect to movement and BFA-induced fusion with the ER. In addi- tion, we propose that a combination of dual-label fluorescence microscopy and drug treatments can provide a simple alternative approach to the determination of protein localization to specific Golgi sub-compartments.

关键词： Golgi apparatus Golgi stack integrity brefeldin a monensin tobacco BY-2 cells live-cell imaging.

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Synthesis and biological evaluation of brefeldin a derivatives as potential anticancer agents

Synthesis and biological evaluation of brefeldin A derivativ...

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中国化学会第十二届全国天然有机化学学术会议

作者： Tong Han Da-Hong Li Zhan-Lin Li Hui-Ming Hua Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education Shenyang Pharmaceutical University

brefeldin a is a 16-membered macrolide antibiotic which was first isolated from Penicillium *** shows a wide variety of biological properties,including antitumor,antifungal,antimitotic and antiviral *** aim of this study was to synthesis brefeldin a derivatives and investigate their antitumor activity.A series of conjugates of brefeldin a were obtained by introducing a variety of active small molecular fragments at 4-OH or 7-OH *** cytotoxic activities of target hybrids against three human cancer cell lines(HL-60 human leukemic cell line,PC-3 human prostatic cancer cell line and Bel-7402 hepatocellular carcinoma cell line),the multidrug resistant cell line Bel-7402/5-FU and the human normal hepatic cell line(L-O2) were screened and compared with lead compound BFA and positive control 5-FU in each *** all the target compounds showed cytotoxic activities against one or more cell ***,one compound displayed the most potent cytotoxic activity among all the ***,it displayed lower toxicity than brefeldin a(IC <0.001 μM) against normal human liver L-O2 cells,showing good selectivity between normal and malignant liver *** summary,novel derivatives of BFA were obtained by introducing molecular fragments at 4-OH and/or *** deserved further investigation as potential chemotherapeutic agents for cancer.

关键词： brefeldin a Antiproliferative activity Selectivity

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海洋真菌Penicillium sp.产抗肿瘤天然产物brefeldin a的发酵优化研究

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中国海洋药物 2022年第2期41卷 14-18页

作者：武艳伟张群滕云飞姜瑶瑶邵长伦魏美燕中国海洋大学海洋药物教育部重点实验室医药学院山东青岛266003 中国海洋大学食品科学与工程学院山东青岛266003

目的对海洋来源真菌Penicillium sp.产抗肿瘤天然产物brefeldin a进行发酵优化,以期获得高产率目标化合物。方法运用单因素实验设计,重点考察了培养方式、发酵培养基组成(如碳源、氮源、盐度等)以及培养条件(温度、摇床转速)等因素。... 详细信息

目的对海洋来源真菌Penicillium sp.产抗肿瘤天然产物brefeldin a进行发酵优化,以期获得高产率目标化合物。方法运用单因素实验设计,重点考察了培养方式、发酵培养基组成(如碳源、氮源、盐度等)以及培养条件(温度、摇床转速)等因素。结果最佳发酵条件为:马铃薯200 g/L,麦芽糖10 g/L,淀粉20 g/L,海盐15 g/L,28℃,摇床转速160 r/min,培养14 d。结论在该发酵条件下,brefeldin a的实际产量达到40 mg/L,较优化前提高了近10倍。

关键词：海洋来源真菌 brefeldin a 发酵条件优化

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Discovery of a potential bladder cancer inhibitor CHNQD-01281 by regulating EGFR and promoting infiltration of cytotoxic T cells

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Marine Life Science & Technology 2024年第3期6卷 502-514页

作者： Jian-Yu Liu Yao-Yao Jiang Peng-Jie Li Bo Yao Yi-Jing Song Ji-Xiu Gao Gulab Said Yang Gao Jun-Yu Lai Chang-Lun Shao Key Laboratory of Marine Drugs the Ministry of Education of ChinaSchool of Medicine and PharmacyOcean University of ChinaQingdao 266003China Department of Critical Care Medicine the Affiliated Hospital of Qingdao UniversityQingdao 266003China Department of Chemistry Women University SwabiSwabi 23430Pakistan Laoshan Laboratory Qingdao 266237China Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education College of Chemistry and Chemical EngineeringHainan Normal UniversityHaikou 571158China

As one of the common malignancies that threaten human life,bladder cancer occurs frequently with a high mortality rate in the world,due to its invasion,recurrence and drug *** products from marine microorganisms are becoming the hotspots in discovery of new candidate drug entities,especially in the area of *** A(BFA)is a natural Arf-GEFs inhibitor,but due to the low aqueous solubility,strong toxicity,and poor bioavailability,it is urgent to conduct structural optimization ***,a new BFA pyridine acrylate derivative CHNQD-01281 with improved solubility was prepared and found to exert moderate to strong antiproliferative activity on a variety of human cancer cell *** was noteworthy that CHNQD-01281 was most sensitive to two bladder cancer cell lines T24 and J82(IC50=0.079 and 0.081μmol/L)with high selectivity index(SI=14.68 and 14.32),suggesting a superior safety to *** vivo studies revealed that CHNQD-01281 remarkably suppressed tumor growth in a T24 nude mice xenograft model(TGI=52.63%)and prolonged the survival time(ILS=68.16%)in an MB49 allogeneic mouse model via inducing infiltration of cytotoxic T *** mechanism exploration indicated that CHNQD-01281 regulated both EGFR/PI3K/AKT and EGFR/ERK pathways and mediated the chemotactic effect of chemokines on immune effector ***,CHNQD-01281 may serve as a potential therapeutic agent for bladder cancer through multiple mechanisms.

关键词： Bladder cancer Marine natural products brefeldin a EGFR/PI3K/AKT EGFR/ERK T-cell infiltration

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Morphology of platelet Golgi apparatus and their significance after acute cerebral infarction

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Neural Regeneration Research 2013年第23期8卷 2134-2143页

作者： Wei Lu Dong Xu Ranran Tu Zhiping Hu Department of Neurology Second Xiangya HospitalCentral South University

Blood samples were harvested from the antecubital vein of 20 fasting patients with acute cerebral infarction at 1, 7 and 15 days after onset to prepare blood platelet suspension. Fasting antecubital vein blood was collected from an additional 20 normal adults as controls. Under transmission elec- tron microscope, platelet Golgi tubules and vesicles became significantly thickened, enlarged, and irregular after acute cerebral infarction. Alpha granules in platelets significantly reduced in number, especially 1 day after cerebral infarction. Under immunoelectron microscopy, a few alpha granules aggregated around Golgi tubules and vesicles after infarction. These results suggested that platelet Golgi apparatus displayed significant morphological changes, which were possibly associated with enhanced synthetic and secretory functions of activated platelets after acute cerebral infarction. This study used Golgi apparatus blocking agent brefeldin a to block Golgi apparatus in an aim to study the effects of Golgi apparatus on CD40L expression on the surface of activated platelets. Flow cytometry revealed that CD40L expression on activated platelet surfaces decreased significantly when Golgi apparatus was blocked, which indicated that Golgi apparatus participated in the syn- thesis and transport of CD40L to the platelet surface.

关键词： neural regeneration brain injury Golgi apparatus CD40L alpha granules platelet ultrastructure cerebral infarction transport secretion brefeldin a grants-supported paper neuroregeneration

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Antifungal Secondary Metabolites Isolated from Mangrove Rhizosphere Soil-Derived Penicillium Fungi

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Journal of Ocean University of China 2020年第3期19卷 717-721页

作者： SHEN Nanxing LIANG Zhaoyang LIU Qing TU Chuandeng DONG Kunming WANG Changyun CHEN Min Marine Science&Technology Institute College of Environmental Science&EngineeringYangzhou UniversityYangzhou 225127China Key Laboratory of Marine Drugs the Ministry of Education of ChinaSchool of Medicine and PharmacyOcean University of ChinaQingdao 266003China Laboratory for Marine Drugs and Bioproducts Qingdao National Laboratory for Marine Science and TechnologyQingdao 266237China

Fungi isolated from mangrove rhizosphere soil of the South China Sea were investigated for the production of potential antifungal metabolites. With 28 fungal isolates, the strains Penicillium javanicum HK1-23 and P. janthinellum HK1-6 showed significant antifungal activities. A bioassay-guided investigation of the two fungal strains led to the isolation of two secondary metabolites, brefeldin a and penicillic acid, with high yields of 143 and 423 mg L^-1, respectively. Penicillic acid showed potent antifungal activities toward Rhizoctonia solani and R. cerealis, with 67.5% and 76% growth inhibition, respectively, at 50 μg mL^-1. brefeldin a showed strong activity toward R. cerealis, with 56.4% growth inhibition at 50 μg mL^-1. The research highlights the importance of exploring microbes from mangrove rhizosphere soil for the identification of bioactive metabolites for future fungicide development.

关键词： mangrove rhizosphere soil-derived fungus Penicillium brefeldin a penicillic acid antifungal

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