【目的】明确TOR(Target of Rapamycin)信号通路抑制剂雷帕霉素对荔枝霜疫霉生长发育、致病性及自噬的影响。【方法】采用不同浓度的TOR抑制剂雷帕霉素处理荔枝霜疫霉菌,观察不同浓度雷帕霉素对荔枝霜疫霉的菌丝生长及形态、孢子囊产生...【目的】明确TOR(Target of Rapamycin)信号通路抑制剂雷帕霉素对荔枝霜疫霉生长发育、致病性及自噬的影响。【方法】采用不同浓度的TOR抑制剂雷帕霉素处理荔枝霜疫霉菌,观察不同浓度雷帕霉素对荔枝霜疫霉的菌丝生长及形态、孢子囊产生数量、游动孢子释放和致病性的影响,并通过丹酰戊二胺(MDC)染色观察细胞自噬。【结果】雷帕霉素处理后,荔枝霜疫霉的菌丝生长明显受到抑制,半最大效应浓度(EC 50)值为29.18 ng·mL^(−1),随着雷帕霉素浓度的增加,菌丝生长抑制不同程度增加;当雷帕霉素深度为25.0 ng·mL^(−1)时,菌落生长抑菌率为45.3%,孢子囊产生数量为8.0×10^(4)个·mL^(−1),仅为对照组的27.9%;雷帕霉素处理能促进游动孢子的释放;同时严重影响荔枝霜疫霉菌的致病性。通过自噬体观察表明,雷帕霉素处理后荔枝霜疫霉菌丝中自噬体的数量显著增加,促进荔枝霜疫霉的细胞自噬。【结论】TOR抑制剂雷帕霉素通过调控荔枝霜疫霉的细胞自噬,从而影响病菌的生长发育及致病性,研究结果为荔枝霜疫霉的致病机制提供科学依据。展开更多
TOR(target of rapamycin)是真核细胞中一种高度保守的与磷脂酰肌醇激酶相关的蛋白激酶(PIKK),它是免疫抑制剂/抗癌药物雷帕霉素(rapamycin)的靶物质。TOR是细胞生长的中枢控制因子,外界营养因素通过TOR的作用控制酵母、果蝇和哺乳动物...TOR(target of rapamycin)是真核细胞中一种高度保守的与磷脂酰肌醇激酶相关的蛋白激酶(PIKK),它是免疫抑制剂/抗癌药物雷帕霉素(rapamycin)的靶物质。TOR是细胞生长的中枢控制因子,外界营养因素通过TOR的作用控制酵母、果蝇和哺乳动物细胞的生长。TOR根据细胞环境的营养条件做出相应的应答,参与调控蛋白激酶和蛋白磷酸酯酶的活性,从而控制与蛋白质合成和基因转录相关基因的表达。现对酵母细胞中TOR信号转导途径的研究进行简明的阐述。展开更多
Glioblastoma(GBM) is one of the most lethal human cancers. Genomic analyses define the molecular architecture of GBM and highlight a central function for mechanistic target of rapamycin(m TOR) signaling. m TOR kinase ...Glioblastoma(GBM) is one of the most lethal human cancers. Genomic analyses define the molecular architecture of GBM and highlight a central function for mechanistic target of rapamycin(m TOR) signaling. m TOR kinase exists in two multiprotein complexes, namely, m TORC1 and m TORC2. These complexes differ in terms of function, regulation and rapamycin sensitivity. m TORC1 is well established as a cancer drug target, whereas the functions of m TORC2 in cancer, including GBM, remains poorly understood. This study reviews the recent findings that demonstrate a central function of m TORC2 in regulating tumor growth, metabolic reprogramming, and targeted therapy resistance in GBM, which makes m TORC2 as a critical GBM drug target.展开更多
文摘TOR(target of rapamycin)是真核细胞中一种高度保守的与磷脂酰肌醇激酶相关的蛋白激酶(PIKK),它是免疫抑制剂/抗癌药物雷帕霉素(rapamycin)的靶物质。TOR是细胞生长的中枢控制因子,外界营养因素通过TOR的作用控制酵母、果蝇和哺乳动物细胞的生长。TOR根据细胞环境的营养条件做出相应的应答,参与调控蛋白激酶和蛋白磷酸酯酶的活性,从而控制与蛋白质合成和基因转录相关基因的表达。现对酵母细胞中TOR信号转导途径的研究进行简明的阐述。
基金supported by grants from the National Institute for Neurological Diseases and Stroke(NS73831)the National Cancer Institute(CA151819)+1 种基金The Ben and Catherine Ivy Foundation,the Defeat GBM Research Collaborative,a subsidiary of National Brain Tumor Societyby the generous donations from the Ziering Family Foundation in memory of Sigi Ziering
文摘Glioblastoma(GBM) is one of the most lethal human cancers. Genomic analyses define the molecular architecture of GBM and highlight a central function for mechanistic target of rapamycin(m TOR) signaling. m TOR kinase exists in two multiprotein complexes, namely, m TORC1 and m TORC2. These complexes differ in terms of function, regulation and rapamycin sensitivity. m TORC1 is well established as a cancer drug target, whereas the functions of m TORC2 in cancer, including GBM, remains poorly understood. This study reviews the recent findings that demonstrate a central function of m TORC2 in regulating tumor growth, metabolic reprogramming, and targeted therapy resistance in GBM, which makes m TORC2 as a critical GBM drug target.
