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Mammalian Ste20-like kinases 1 and 2 (MST1 and MST2) are activated in NIH3T3 cells exposed to okadaic acid. The Hippo pathway is a newly emerging signaling that functions as a tumor suppressor. MST1 and MST2 work as core kinases of the Hippo pathway and their activities depend on the autophosphorylation, which is negatively regulated by protein phosphatase 2A (PP2A). Okadaic acid has been frequently used to enhance the phosphorylation of MST1 and MST2 and to trigger the activation of the Hippo pathway. However other components of the Hippo pathway could also be targets of okadaic acid. In this review we first briefly summarize the molecular architecture of the Hippo pathway for the reference of researchers outside the field. We explain how MST kinases are regulated by PP2A and how okadaic acid activates MST2. Thereafter we discuss which components of the Hippo pathway are candidate substrates of protein phosphatases and which points we need to consider in the usage of okadaic acid to study the Hippo pathway. 相似文献
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泛素蛋白酶体途径(UPP)是真核生物细胞内最重要的、具有高度选择性的蛋白质降解途径,该途径几乎在植物生长发育的各个方面发挥作用,包括激素信号传导、自交不亲和、抗病、表观遗传、形态建成等过程。本文综述UPP途径在植物激素合成及其信号转导的调控研究方面取得的最新研究进展。 相似文献
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茉莉酸类物质在调节植物对逆境的反应和生长发育方面有重要作用.最近,从模式植物拟南芥中分离鉴定了茉莉酸响应基因的转录抑制因子JAZ(茉莉酸ZIM结构域蛋白)蛋白家族的12个成员,这是植物茉莉酸信号途径分子机制研究的重大进展.JAZ蛋白不仅是联系COI1和下游茉莉酸反应基因的环节,而且COI1-JAZ蛋白的相互作用导致发现活性形式的茉莉酸类物质及其受体.笔者综述了JAZ蛋白家族的结构特点、不同成员之间及其与MYC转录因子之间的相互作用,以及JAZ蛋白对茉莉酸响应基因的转录调节机制,并展望其在橡胶生物合成中的调节作用. 相似文献
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为探究微生物作用下咖啡碱的降解产物与途径,将普洱茶发酵中筛选鉴定的Aspergillus sydowii NRRL250（聚多曲霉）、Aspergillus pallidofulvus NRRL4789、Aspergillus sesamicola CBS137324和Penicillium mangini CBS253.31等优势菌株分别接种至晒青毛茶进行单菌种固态发酵,并采用高效液相色谱（HPLC）测定咖啡碱、可可碱、茶碱的含量,探究微生物对咖啡碱代谢的影响;另外,基于UHPLC-QTOF-MS代谢组学技术,以灭菌处理组（ST组）和原料组（RM组）为对照,对聚多曲霉接种发酵样进行代谢组学分析。结果表明,A. pallidofulvus NRRL4789、A. sesamicola CBS137324和Penicillium mangini CBS253.31等优势菌株对咖啡碱等嘌呤类碱代谢均无显著影响,而在聚多曲霉接种发酵中,咖啡碱含量显著下降（P<0.05）,降幅达83.89%;茶碱含量显著增加（P<0.05）,发酵末期含量为(25.03±1.17) mg·g-1;而可可碱保持基本稳定。由此可知,聚多曲霉对咖啡碱降解代谢有显著影响。采用UHPLC-QTOF-MS方法检出茶碱、3-甲基黄嘌呤、1,7-二甲基黄嘌呤等9种与咖啡碱降解相关的代谢物。在聚多曲霉作用下,茶碱、3-甲基黄嘌呤、1,7-二甲基黄嘌呤、7-甲基黄嘌呤含量显著提高（P<0.05）。茶碱、3-甲基黄嘌呤、1,7-二甲基黄嘌呤和1-甲基黄嘌呤与咖啡碱及其相关代谢物的N-脱甲基化途径相关。1,7-二甲基尿酸、1-甲基尿酸与咖啡碱相关代谢物的氧化途径相关。由此可知,聚多曲霉为降解普洱茶咖啡碱的优势菌株,且具有将咖啡碱转化为茶碱的潜在能力;在咖啡碱降解代谢过程中,存在聚多曲霉作用下的N-脱甲基化和氧化,并以N-脱甲基化为主。 相似文献
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小麦光呼吸途径电子流分配的模型研究 总被引：1，自引：0，他引：1
为探讨分配到植物光呼吸的光合电子流(J_o)对CO_2浓度(J_o-C_a曲线)的响应规律,以小麦Z39-118为材料,分析了小麦叶片在2%和21%O_2浓度下的光合速率(A_c)和电子传递速率(J)对CO_2浓度的响应曲线。结果表明,光合作用对CO_2浓度的响应新模型(模型I)可很好地拟合小麦的A_c对CO_2浓度响应曲线;同样,基于模型I而构建的J对CO_2的响应模型(模型II),也可很好地拟合小麦在21%和2%O_2条件下的J对CO_2响应曲线。利用模型II分别拟合基于传统公式(J_o=2[J-4(A_c+R_(day))]/3)得到的J_o-C_a曲线(R_(day)为日呼吸速率)及基于光呼吸速率值而计算得到的J_o-C_a曲线,结果显示,两者拟合得到的分配到光呼吸的最大电子传递速率值(分别为86.93和84.17μmol·m~(-2)·s~(-1))与实测值(89.12μmol·m~(-2)·s~(-1))均较为接近(P0.05);但基于前者拟合所得到的饱和CO_2浓度和CO_2为0μmol·mol~(-1)时分配到光呼吸的电子传递速率,均与其对应的测量值之间均存在显著差异(P0.05)。综合分析认为,传统用于计算参与光呼吸途径的光合电子流公式并不能准确地描述J_o对CO_2浓度的响应趋势,本研究构建的新模型可准确地定量研究光呼吸及其电子流分配等问题。 相似文献
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Floridoside Extracted from the Red Alga Mastocarpus stellatus Is a Potent Activator of the Classical Complement Pathway 
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下载免费PDF全文 Anthony Courtois Christelle Simon-Colin Claire Boisset Christian Berthou Eric Deslandes Jean Guézennec Anne Bordron 《Marine drugs》2008,6(3):407-417
Many biological properties of algae have been found to have useful applications in human health, particularly in the fields of oncology and immunology. Floridoside, extracted from the red alga Mastocarpus stellatus, has a structure similar to the xenoantigen Gal alpha 1–3 Gal. This xenoantigen has been described to induce a high immune response in human xenografts and is mediated by natural anti-gal antibodies that activate the classical complement pathway. Based on this property, we analyzed the potential activities of floridoside on the immune system. We demonstrated that floridoside activates a complement cascade via the classical complement pathway, through the recruitment and activation of natural IgM. This algal molecule could represent an important step in the development of a potent new anticomplementary agent for use in therapeutic complement depletion. 相似文献
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硫醇广泛存在于巴西橡胶树胶乳中，其主要成分为还原型谷胱甘肽(GSH)，在橡胶树产排胶和死皮中发挥重要作用。γ-谷氨酰半胱氨酸合成酶(γGCS)是催化GSH生物合成的限速酶，谷胱甘肽还原酶(GR)在NADPH作用下催化氧化型谷胱甘肽(GSSG)还原为还原型GSH。GSH的抗氧化能力很大程度上取决于其在胞内的浓度及GSH/GSSG的比率。本研究发现健康橡胶树胶乳中的硫醇含量、γGCS和GR活性高于死皮树。H2O2能增加PR107、RY7-33-97和RRIM600 3个品系橡胶树幼苗叶片中GSH/GSSG比例、γGCS和GR活性，其中RRIM600上调最为明显，PR107变化最小。研究结果为进一步揭示硫醇在产排胶和死皮中的作用提供了实验证据，同时也为阐明橡胶树活性氧与死皮的关系奠定了基础。 相似文献
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Shih-Wei Lin Shih-Chung Huang Hsiao-Mei Kuo Chiu-Hua Chen Yi-Ling Ma Tian-Huei Chu Youn-Shen Bee E-Ming Wang Chang-Yi Wu Ping-Jyun Sung Zhi-Hong Wen Deng-Chyang Wu Jyh-Horng Sheu Ming-Hong Tai 《Marine drugs》2015,13(2):861-878
Background: WA-25 (dihydroaustrasulfone alcohol, a synthetic derivative of marine compound WE-2) suppresses atherosclerosis in rats by reducing neointima formation. Because angiogenesis plays a critical role in the pathogenesis of atherosclerosis, the present study investigated the angiogenic function and mechanism of WA-25. Methods: The angiogenic effect of WA-25 was evaluated using a rat aortic ring assay and transgenic zebrafish models were established using transgenic Tg(fli-1:EGFP)y1 and Tg(kdrl:mCherryci5-fli1a:negfpy7) zebrafish embryos. In addition, the effect of WA-25 on distinct angiogenic processes, including matrix metalloproteinase (MMP) expression, endothelial cell proliferation and migration, as well as tube formation, was studied using human umbilical vein endothelial cells (HUVECs). The effect of WA-25 on the endothelial vascular endothelial growth factor (VEGF) signaling pathway was elucidated using qRT-PCR, immunoblot analysis, immunofluorescence and flow cytometric analyses. Results: The application of WA-25 perturbed the development of intersegmental vessels in transgenic zebrafish. Moreover, WA-25 potently suppressed microvessel sprouting in organotypic rat aortic rings. Among cultured endothelial cells, WA-25 significantly and dose-dependently inhibited MMP-2/MMP-9 expression, proliferation, migration and tube formation in HUVECs. Mechanistic studies revealed that WA-25 significantly reduced the VEGF release by reducing VEGF expression at the mRNA and protein levels. In addition, WA-25 reduced surface VEGF receptor 2 (VEGFR2/Flk-1) expression by repressing the VEGFR2 mRNA level. Finally, an exogenous VEGF supply partially rescued the WA-25-induced angiogenesis blockage in vitro and in vivo. Conclusions: WA-25 is a potent angiogenesis inhibitor that acts through the down-regulation of VEGF and VEGFR2 in endothelial cells. General
Significance: WA-25 may constitute a novel anti-angiogenic drug that acts by targeting endothelial VEGF/VEGFR2 signaling. 相似文献
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Beatriz Mart��nez-Poveda Salvador Rodr��guez-Nieto Melissa Garc��a-Caballero Miguel-��ngel Medina Ana R. Quesada 《Marine drugs》2012,10(9):2033-2046
Aeroplysinin-1 is a brominated metabolite extracted from the marine sponge Aplysina aerophoba that has been previously characterized by our group as a potent antiangiogenic compound in vitro and in vivo. In this work, we provide evidence of a selective induction of apoptosis by aeroplysinin-1 in endothelial cells. Studies on the nuclear morphology of treated cells revealed that aeroplysinin-1 induces chromatin condensation and nuclear fragmentation, and it increases the percentage of cells with sub-diploid DNA content in endothelial, but not in HCT-116, human colon carcinoma and HT-1080 human fibrosarcoma cells. Treatment of endothelial cells with aeroplysinin-1 induces activation of caspases-2, -3, -8 and -9, as well as the cleavage of apoptotic substrates, such as poly (ADP-ribose) polymerase and lamin-A in a caspase-dependent mechanism. Our data indicate a relevant role of the mitochondria in the apoptogenic activity of this compound. The observation that aeroplysinin-1 prevents the phosphorylation of Bad relates to the mitochondria-mediated induction of apoptosis by this compound. 相似文献
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Oceanapiside (OPS), a marine natural product with a novel bifunctional sphingolipid structure, is fungicidal against fluconazole-resistant Candida glabrata at 10 μg/mL (15.4 μM). The fungicidal effect was observed at 3 to 4 h after exposure to cells. Cytological and morphological studies revealed that OPS affects the budding patterns of treated yeast cells with a significant increase in the number of cells with single small buds. In addition, this budding morphology was found to be sensitive in the presence of OPS. Moreover, the number of cells with single medium-sized buds and cells with single large buds were decreased significantly, indicating that fewer cells were transformed to these budding patterns, suggestive of inhibition of polarized growth. OPS was also observed to disrupt the organized actin assembly in C. glabrata, which correlates with inhibition of budding and polarized growth. It was also demonstrated that phytosphingosine (PHS) reversed the antifungal activity of oceanapiside. We quantified the amount of long chain-bases (LCBs) and phytoceramide from the crude extracts of treated cells using LC-ESI-MS. PHS concentration was elevated in extracts of cells treated with OPS when compared with cells treated with miconazole and amphotericin B. Elevated levels of PHS in OPS-treated cells confirms that OPS affects the pathway at a step downstream of PHS synthesis. These results also demonstrated that OPS has a mechanism of action different to those of miconazole and amphotericin B and interdicts fungal sphingolipid metabolism by specifically inhibiting the step converting PHS to phytoceramide. 相似文献