自噬活化在软骨细胞中对线粒体失调的保护作用  

Activation of autophagy protects against mitochondrial dysfunction in human chondrocytes

作　　者：刘柱[1] 范清[1] 陈珽[1] 沈品泉[1] 杨璇[1] 张自明[1] 

机构地区：[1]上海交通大学医学院附属新华医院,上海200092

出　　处：《临床和实验医学杂志》2016年第6期526-530,共5页Journal of Clinical and Experimental Medicine

基　　金：上海市科学技术委员会课题;上海市自然科学基金(编号:13ZR1427000)

摘　　要：目的明确自噬活化在人软骨细胞线粒体功能失调中的保护作用。方法采用线粒体呼吸链抑制剂oligomycin处理人软骨细胞,通过分析LC3-II分析自噬体活化。通过采用自噬激活剂Rapamycin和Torin处理人软骨细胞,分析自噬对oligomycin介导的线粒体功能失调的保护作用。结果 oligomycin处理能够导致人软骨细胞线粒体功能失调,从而导致凋亡和死亡的显著增加。此外,细胞自噬的激活也在oligomycin处理的细胞中被观察到。采用自噬激活剂Rapamycin和Torin处理人软骨细胞,能够对线粒体功能起到保护作用。结论自噬在人软骨细胞线粒体功能失调中具有保护作用。自噬相关药物的介入可能对软骨细胞具有保护作用。Objective The objective of this study was to determine whether activation of autophagy protects against mitochondrial dysfunction in human chondrocytes. Methods Human chondrocytes were treated with oligomycin,an inhibitor of mitochondrial respiratory chain complex V. Autophagy activation was analyzed by determination of light chain 3 membrane- bound form II（ LC3- II）,a marker of autophagosome formation. To investigate whether autophagy protects from mitochondrial dysfunction,autophagy was induced by rapamycin,the selective inhibitor of mammalian target of rapamycin complex 1（ m TORC- 1）,and by torin 1,the inhibitor of m TORC- 1 and m TORC- 2. Results Mitochondrial dysfunction was induced by treatment with oligomycin,which was associated with increased production of reactive oxygen species and cell death.Autophagy activation,as reflected by LC3- II,decreased in a time- dependent manner. To evaluate whether autophagy regulates mitochondrial function,chondrocytes were pretreated with rapamycin and torin 1 before oligomycin. Autophagy activation significantly protected against mitochondrial dysfunction. Conclusion Our data highlight the role of autophagy as a critical protective mechanism against mitochondrial dysfunction.Pharmacologic interventions that enhance autophagy may have chondro- protective activity in cartilage degenerative processes,such as OA.

关 键 词：软骨细胞 自噬 线粒体失调 保护作用 

分 类 号：R684.3[医药卫生—骨科学]