背景:运动作为一种可行的非药物治疗方法,有可能逆转随着年龄增长而恶化的骨骼肌衰老。自噬在骨骼肌衰老过程中的作用是不可缺少的。在骨骼肌衰老期间,参与调节自噬的Atg基因以或促进或抑制的方式调节自噬过程,以改善骨骼肌的生理形态...背景:运动作为一种可行的非药物治疗方法,有可能逆转随着年龄增长而恶化的骨骼肌衰老。自噬在骨骼肌衰老过程中的作用是不可缺少的。在骨骼肌衰老期间,参与调节自噬的Atg基因以或促进或抑制的方式调节自噬过程,以改善骨骼肌的生理形态。然而自噬在运动调节骨骼肌衰老中的具体分子机制仍令人困惑。目的:通过对该领域文献的回顾,寻找运动中自噬机制对骨骼肌衰老影响的一般规律。方法:①文献资料法:通过对CNKI及Web of Science数据库有关“Atg基因(蛋白)、自噬、运动以及骨骼肌衰老”等相关文献的检索、查阅和筛选,为全文的分析奠定理论基础。②对比分析法:通过对所得到文献进行阅读分析,比较文献之间的异同点,为论点提供合理的理论支撑;通过对文献的进一步对比分析,理清相关指标间的关系,为全文的分析明确思路。结果与结论:Atg家族介导的自噬对于延缓骨骼肌衰老是不可或缺的。参与调节自噬的Atg基因以或促进或抑制的方式调节自噬过程,以改善骨骼肌的生理形态及功能。不同的运动模式,如开始运动的年龄、时间或者强度,可能对自噬相关蛋白的表达有异质性的影响,但长期的有氧运动可以调节Atg相关蛋白,诱导骨骼肌自噬,并延缓肌肉质量的损失。展开更多
Background:Myocardial infarction(MI)is an acute condition in which the heart mus-cle dies due to the lack of blood supply.Previous research has suggested that au-tophagy and angiogenesis play vital roles in the preven...Background:Myocardial infarction(MI)is an acute condition in which the heart mus-cle dies due to the lack of blood supply.Previous research has suggested that au-tophagy and angiogenesis play vital roles in the prevention of heart failure after MI,and miR-106a is considered to be an important regulatory factor in MI.But the specific mechanism remains unknown.In this study,using cultured venous endothelial cells and a rat model of MI,we aimed to identify the potential target genes of miR-106a and discover the mechanisms of inhibiting autophagy and angiogenesis.Methods:We first explored the biological functions of miR-106a on autophagy and angiogenesis on endothelial cells.Then we identified ATG7,which was the down-stream target gene of miR-106a.The expression of miR-106a and ATG7 was investi-gated in the rat model of MI.Results:We found that miR-106a inhibits the proliferation,cell cycle,autophagy and angiogenesis,but promoted the apoptosis of vein endothelial cells.Moreover,ATG7 was identified as the target of miR-106a,and ATG7 rescued the inhibition of autophagy and angiogenesis by miR-106a.The expression of miR-106a in the rat model of MI was decreased but the expression of ATG7 was increased in the infarction areas.Conclusion:Our results indicate that miR-106a may inhibit autophagy and angiogenesis by targeting ATG7.This mechanism may be a potential therapeutic treatment for MI.展开更多
Parkinson’s disease is a progressive neurodegenerative disease characterized by motor deficits,dopaminergic neuron loss,and brain accumulation ofα-synuclein aggregates called Lewy bodies.Dysfunction in protein degra...Parkinson’s disease is a progressive neurodegenerative disease characterized by motor deficits,dopaminergic neuron loss,and brain accumulation ofα-synuclein aggregates called Lewy bodies.Dysfunction in protein degradation pathways,such as autophagy,has been demonstrated in neurons as a critical mechanism for eliminating protein aggregates in Parkinson’s disease.However,it is less well understood how protein aggregates are eliminated in glia,the other cell type in the brain.In the present study,we show that autophagy-related gene 9(Atg9),the only transmembrane protein in the autophagy machinery,is highly expressed in Drosophila glia from adult brain.Results from immunostaining and live cell imaging analysis reveal that a portion of Atg9 localizes to the trans-Golgi network,autophagosomes,and lysosomes in glia.Atg9 is persistently in contact with these organelles.Lacking glial atg9 reduces the number of omegasomes and autophagosomes,and impairs autophagic substrate degradation.This suggests that glial Atg9 participates in the early steps of autophagy,and hence the control of autophagic degradation.Importantly,loss of glial atg9 induces parkinsonian symptoms in Drosophila including progressive loss of dopaminergic neurons,locomotion deficits,and glial activation.Our findings identify a functional role of Atg9 in glial autophagy and establish a potential link between glial autophagy and Parkinson’s disease.These results may provide new insights on the underlying mechanism of Parkinson’s disease.展开更多
2024年4月16日,上海交通大学基础医学院病理生理学系钟清、留筱厦课题组在Cell Discovery在线发表题为ANKFY1 bridges ATG2A-mediated lipid transfer from endosomes to phagophores的研究论文,发现ANKFY1(含有Ankyrin重复和FYVE结构蛋...2024年4月16日,上海交通大学基础医学院病理生理学系钟清、留筱厦课题组在Cell Discovery在线发表题为ANKFY1 bridges ATG2A-mediated lipid transfer from endosomes to phagophores的研究论文,发现ANKFY1(含有Ankyrin重复和FYVE结构蛋白1)可以将自噬相关蛋白2A(autophagy related 2A,ATG2A)锚定在内体上,协助ATG2A转运内体上的脂质到自噬小体上,从而促进自噬体的膜延伸。该研究阐明了ATG2A作为脂质转运过程中的关键蛋白介导内体与自噬体间脂质转运的分子机制,为内体作为自噬体膜来源提供了有力证据。展开更多
文摘背景:运动作为一种可行的非药物治疗方法,有可能逆转随着年龄增长而恶化的骨骼肌衰老。自噬在骨骼肌衰老过程中的作用是不可缺少的。在骨骼肌衰老期间,参与调节自噬的Atg基因以或促进或抑制的方式调节自噬过程,以改善骨骼肌的生理形态。然而自噬在运动调节骨骼肌衰老中的具体分子机制仍令人困惑。目的:通过对该领域文献的回顾,寻找运动中自噬机制对骨骼肌衰老影响的一般规律。方法:①文献资料法:通过对CNKI及Web of Science数据库有关“Atg基因(蛋白)、自噬、运动以及骨骼肌衰老”等相关文献的检索、查阅和筛选,为全文的分析奠定理论基础。②对比分析法:通过对所得到文献进行阅读分析,比较文献之间的异同点,为论点提供合理的理论支撑;通过对文献的进一步对比分析,理清相关指标间的关系,为全文的分析明确思路。结果与结论:Atg家族介导的自噬对于延缓骨骼肌衰老是不可或缺的。参与调节自噬的Atg基因以或促进或抑制的方式调节自噬过程,以改善骨骼肌的生理形态及功能。不同的运动模式,如开始运动的年龄、时间或者强度,可能对自噬相关蛋白的表达有异质性的影响,但长期的有氧运动可以调节Atg相关蛋白,诱导骨骼肌自噬,并延缓肌肉质量的损失。
基金National Natural Science Foundation of China,Grant/Award Number:32070542Guangdong Basic and Applied Basic Research Foundation,Grant/Award Number:2021A1515010873 and 2022A1515011455+1 种基金Breed Industry Innovation Park of Guangdong Xiaoerhua Pig,Grant/Award Number:2022-4408X1-43010402-0019Hainan Provincial Natural Science Foundation,Grant/Award Number:818MS132。
文摘Background:Myocardial infarction(MI)is an acute condition in which the heart mus-cle dies due to the lack of blood supply.Previous research has suggested that au-tophagy and angiogenesis play vital roles in the prevention of heart failure after MI,and miR-106a is considered to be an important regulatory factor in MI.But the specific mechanism remains unknown.In this study,using cultured venous endothelial cells and a rat model of MI,we aimed to identify the potential target genes of miR-106a and discover the mechanisms of inhibiting autophagy and angiogenesis.Methods:We first explored the biological functions of miR-106a on autophagy and angiogenesis on endothelial cells.Then we identified ATG7,which was the down-stream target gene of miR-106a.The expression of miR-106a and ATG7 was investi-gated in the rat model of MI.Results:We found that miR-106a inhibits the proliferation,cell cycle,autophagy and angiogenesis,but promoted the apoptosis of vein endothelial cells.Moreover,ATG7 was identified as the target of miR-106a,and ATG7 rescued the inhibition of autophagy and angiogenesis by miR-106a.The expression of miR-106a in the rat model of MI was decreased but the expression of ATG7 was increased in the infarction areas.Conclusion:Our results indicate that miR-106a may inhibit autophagy and angiogenesis by targeting ATG7.This mechanism may be a potential therapeutic treatment for MI.
基金supported by the National Natural Science Foundation of China,Nos.31871039 and 32170962(to MSH).
文摘Parkinson’s disease is a progressive neurodegenerative disease characterized by motor deficits,dopaminergic neuron loss,and brain accumulation ofα-synuclein aggregates called Lewy bodies.Dysfunction in protein degradation pathways,such as autophagy,has been demonstrated in neurons as a critical mechanism for eliminating protein aggregates in Parkinson’s disease.However,it is less well understood how protein aggregates are eliminated in glia,the other cell type in the brain.In the present study,we show that autophagy-related gene 9(Atg9),the only transmembrane protein in the autophagy machinery,is highly expressed in Drosophila glia from adult brain.Results from immunostaining and live cell imaging analysis reveal that a portion of Atg9 localizes to the trans-Golgi network,autophagosomes,and lysosomes in glia.Atg9 is persistently in contact with these organelles.Lacking glial atg9 reduces the number of omegasomes and autophagosomes,and impairs autophagic substrate degradation.This suggests that glial Atg9 participates in the early steps of autophagy,and hence the control of autophagic degradation.Importantly,loss of glial atg9 induces parkinsonian symptoms in Drosophila including progressive loss of dopaminergic neurons,locomotion deficits,and glial activation.Our findings identify a functional role of Atg9 in glial autophagy and establish a potential link between glial autophagy and Parkinson’s disease.These results may provide new insights on the underlying mechanism of Parkinson’s disease.
文摘2024年4月16日,上海交通大学基础医学院病理生理学系钟清、留筱厦课题组在Cell Discovery在线发表题为ANKFY1 bridges ATG2A-mediated lipid transfer from endosomes to phagophores的研究论文,发现ANKFY1(含有Ankyrin重复和FYVE结构蛋白1)可以将自噬相关蛋白2A(autophagy related 2A,ATG2A)锚定在内体上,协助ATG2A转运内体上的脂质到自噬小体上,从而促进自噬体的膜延伸。该研究阐明了ATG2A作为脂质转运过程中的关键蛋白介导内体与自噬体间脂质转运的分子机制,为内体作为自噬体膜来源提供了有力证据。
