Objective:To investigate effect of oleanolic acid(OA)on atherosclerosis and its related mechanisms.Methods:Human umbilical vein endothelial cells(HUVECs)were injured by oxidized low-density lipoprotein for 24 h and tr...Objective:To investigate effect of oleanolic acid(OA)on atherosclerosis and its related mechanisms.Methods:Human umbilical vein endothelial cells(HUVECs)were injured by oxidized low-density lipoprotein for 24 h and treated with OA,and the levels of cell proliferation,migration,adhesion,and apoptosis were evaluated by BrdU staining,scratch healing assay,monocyte-endothelial cell adhesion assay and flow cytometry.The mice were fed with a high-fat diet to induce an atherosclerosis model,and treated with OA by gastric gavage.The mice were divided into the control group,the model group,and the OA administration group.The blood lipid and plaque formation in mice were detected.In addition,oxidative stress and mitochondrial structure and function changes in cells and mice were evaluated by transmission electron microscopy,JC-1 fluorescent probe,and Western blotting assays.The expression levels of proteins in the AMPK/Drp1 pathway were examined through Western blot.Results:OA markedly increased cell viability and migration rate of HUVECs,and decreased the adhesion rate of THP-1 cells and the apoptosis rate.OA significantly reduced serum lipid levels,such as total cholesterol and triglyceride,in mice and inhibited plaque formation in the aorta.OA also significantly increased the content of superoxide dismutase and catalase,alleviated mitochondrial damage,such as mitochondrial swelling and mitochondrial cristae reduction,reduced the number of mitochondria,increased adenosine triphosphate content,and significantly reduced p-Drp1(Ser616)/Drp1,MFF and FIS1 levels,increased p-AMPK/AMPK levels,activated AMPK,and then regulated DRP1 activity.Conclusions:OA activates AMPK,which in turn regulates the activity of DRP1 to restore normal mitochondrial dynamics and reduce atherosclerosis.展开更多
Intervertebral disc degeneration(IVDD)is the primary contributor to a range of spinal diseases.Dynamin-related protein 1(Drp1)-mediated mitochondrial fission has recently been identified as a new cause of nucleus pulp...Intervertebral disc degeneration(IVDD)is the primary contributor to a range of spinal diseases.Dynamin-related protein 1(Drp1)-mediated mitochondrial fission has recently been identified as a new cause of nucleus pulposus cell(NPC)death and IVDD,but the underlying mechanisms remain unclear.Although the effects of Drp1 phosphorylation in IVDD have been studied,it is currently unknown if small ubiquitin-like modifications(SUMOylation)of Drp1 regulate IVDD.This study aimed to investigate the functions and mechanisms of mitochondria-anchored protein ligase(MAPL),a mitochondrial SUMO E3 ligase,during IVDD progression.The expression of genes related to SUMOylation and mitochondrial dynamics in TNF-α-stimulated NPCs was analysed via RNA sequencing.展开更多
线粒体动力相关蛋白(dynamin-related protein 1,Drp1)是介导线粒体分裂的主要蛋白,Drp1表达增加,线粒体分裂增加,网状结构破坏,反之则有助线粒体融合,促进损伤线粒体修复。心肌缺血再灌注损伤与活性氧(ROS)的大量产生,线粒体通透性转换...线粒体动力相关蛋白(dynamin-related protein 1,Drp1)是介导线粒体分裂的主要蛋白,Drp1表达增加,线粒体分裂增加,网状结构破坏,反之则有助线粒体融合,促进损伤线粒体修复。心肌缺血再灌注损伤与活性氧(ROS)的大量产生,线粒体通透性转换孔(MPTP)的开放及细胞凋亡等密切相关。近年来大量研究发现Drp1介导的线粒体分裂参与心肌缺血再灌注损伤,本文就Drp1参与心肌缺血再灌注损伤的相关机制作一简要综述。展开更多
目的:探讨缺氧-复氧(hypoxia/reoxygenation,H/R)后人近曲肾小管上皮细胞(HK-2)内动力相关蛋白1(Dynamin related protein 1,DRP1)及视神经萎缩症蛋白1(optic atrophy,OPA1)表达的变化。方法:以人近曲肾小管上皮细胞株为研究对象,将培...目的:探讨缺氧-复氧(hypoxia/reoxygenation,H/R)后人近曲肾小管上皮细胞(HK-2)内动力相关蛋白1(Dynamin related protein 1,DRP1)及视神经萎缩症蛋白1(optic atrophy,OPA1)表达的变化。方法:以人近曲肾小管上皮细胞株为研究对象,将培养细胞随机分为正常对照组和H/R组。正常对照组常规培养,H/R组先缺氧24h,然后复氧培养6h。光镜观察细胞形态变化,CCK-8检测细胞活力,透射电子显微镜观察线粒体形态改变,免疫组织化学法检测细胞内DRP1和OPA1蛋白表达。结果:H/R组与对照组相比,细胞活力下降,线粒体出现凋亡相关改变,OPA1表达减少而DRP1的表达增加。结论:缺氧-复氧可导致HK-2细胞发生凋亡相关改变,其机制可能与诱导线粒体形态相关蛋白DRP1、OPA1的表达改变相关。展开更多
文摘Objective:To investigate effect of oleanolic acid(OA)on atherosclerosis and its related mechanisms.Methods:Human umbilical vein endothelial cells(HUVECs)were injured by oxidized low-density lipoprotein for 24 h and treated with OA,and the levels of cell proliferation,migration,adhesion,and apoptosis were evaluated by BrdU staining,scratch healing assay,monocyte-endothelial cell adhesion assay and flow cytometry.The mice were fed with a high-fat diet to induce an atherosclerosis model,and treated with OA by gastric gavage.The mice were divided into the control group,the model group,and the OA administration group.The blood lipid and plaque formation in mice were detected.In addition,oxidative stress and mitochondrial structure and function changes in cells and mice were evaluated by transmission electron microscopy,JC-1 fluorescent probe,and Western blotting assays.The expression levels of proteins in the AMPK/Drp1 pathway were examined through Western blot.Results:OA markedly increased cell viability and migration rate of HUVECs,and decreased the adhesion rate of THP-1 cells and the apoptosis rate.OA significantly reduced serum lipid levels,such as total cholesterol and triglyceride,in mice and inhibited plaque formation in the aorta.OA also significantly increased the content of superoxide dismutase and catalase,alleviated mitochondrial damage,such as mitochondrial swelling and mitochondrial cristae reduction,reduced the number of mitochondria,increased adenosine triphosphate content,and significantly reduced p-Drp1(Ser616)/Drp1,MFF and FIS1 levels,increased p-AMPK/AMPK levels,activated AMPK,and then regulated DRP1 activity.Conclusions:OA activates AMPK,which in turn regulates the activity of DRP1 to restore normal mitochondrial dynamics and reduce atherosclerosis.
基金supported by National Natural Science Foundation of China(82272549,82472505,and 82472498)National key Research and Development plan,Ministry of Science and Technology of the People’s Republic of China(2022YFC2407203)+2 种基金the Young Health Talents of Shanghai Municipal Health Commission,China(2022YQ011)China Medical Education Association(3030537245)The Youth Talent Project of Huashan Hospital(30302164006).
文摘Intervertebral disc degeneration(IVDD)is the primary contributor to a range of spinal diseases.Dynamin-related protein 1(Drp1)-mediated mitochondrial fission has recently been identified as a new cause of nucleus pulposus cell(NPC)death and IVDD,but the underlying mechanisms remain unclear.Although the effects of Drp1 phosphorylation in IVDD have been studied,it is currently unknown if small ubiquitin-like modifications(SUMOylation)of Drp1 regulate IVDD.This study aimed to investigate the functions and mechanisms of mitochondria-anchored protein ligase(MAPL),a mitochondrial SUMO E3 ligase,during IVDD progression.The expression of genes related to SUMOylation and mitochondrial dynamics in TNF-α-stimulated NPCs was analysed via RNA sequencing.
文摘线粒体动力相关蛋白(dynamin-related protein 1,Drp1)是介导线粒体分裂的主要蛋白,Drp1表达增加,线粒体分裂增加,网状结构破坏,反之则有助线粒体融合,促进损伤线粒体修复。心肌缺血再灌注损伤与活性氧(ROS)的大量产生,线粒体通透性转换孔(MPTP)的开放及细胞凋亡等密切相关。近年来大量研究发现Drp1介导的线粒体分裂参与心肌缺血再灌注损伤,本文就Drp1参与心肌缺血再灌注损伤的相关机制作一简要综述。
文摘目的:探讨缺氧-复氧(hypoxia/reoxygenation,H/R)后人近曲肾小管上皮细胞(HK-2)内动力相关蛋白1(Dynamin related protein 1,DRP1)及视神经萎缩症蛋白1(optic atrophy,OPA1)表达的变化。方法:以人近曲肾小管上皮细胞株为研究对象,将培养细胞随机分为正常对照组和H/R组。正常对照组常规培养,H/R组先缺氧24h,然后复氧培养6h。光镜观察细胞形态变化,CCK-8检测细胞活力,透射电子显微镜观察线粒体形态改变,免疫组织化学法检测细胞内DRP1和OPA1蛋白表达。结果:H/R组与对照组相比,细胞活力下降,线粒体出现凋亡相关改变,OPA1表达减少而DRP1的表达增加。结论:缺氧-复氧可导致HK-2细胞发生凋亡相关改变,其机制可能与诱导线粒体形态相关蛋白DRP1、OPA1的表达改变相关。
