Ferroptosis is a programmed cell death,and its mechanism involves multiple metabolic pathways,such as iron and lipid metabolism,and redox homeostasis.Exerkines are important mediators that optimize cellular homeostasi...Ferroptosis is a programmed cell death,and its mechanism involves multiple metabolic pathways,such as iron and lipid metabolism,and redox homeostasis.Exerkines are important mediators that optimize cellular homeostasis and maintain physiological health during exercise stim-ulation.This article comprehensively examines the mechanisms and regulatory networks for governing ferroptosis and summarizes the impact of exercise and exerkines on ferroptosis under varying load intensities and disease contexts.Notably,despite its significant efficacy and minimal side effects, the therapeutic and prognostic potential of exercise in ferroptosis-related diseases remains largely unexplored.This article,by summarizing recent progresses in the regulation of exerkines-mediated ferroptosis,could further uncover the preventive or alleviative mecha-nisms of some diseases upon exercise interventions,which will be beneficial to design exercise interventional strategies for alleviating disease progression through the regulation of ferroptosis.展开更多
目的 在动物水平探讨铁死亡脂质过氧化损伤调控通路与帕金森病(Parkinson's disease, PD)的发病机制。方法 建立PD斑马鱼动物模型,取受精后48 h斑马鱼胚胎为对照组(n=100),200μmol/L的1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-p...目的 在动物水平探讨铁死亡脂质过氧化损伤调控通路与帕金森病(Parkinson's disease, PD)的发病机制。方法 建立PD斑马鱼动物模型,取受精后48 h斑马鱼胚胎为对照组(n=100),200μmol/L的1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP)为MPTP组(n=100),200μmol/L的MPTP+1.5μg/ml诺米芬辛为诺米芬辛组(n=100)。对受精后5 d斑马鱼进行行为学分析(检测运动能力、运动速率及运动距离);免疫荧光检测斑马鱼脑内α突触核蛋白和酪氨酸羟化酶表达,评估多巴胺能神经元(dopaminergic neurons, DA)活性;检测铁、谷胱甘肽(glutathione, GSH)及脂质过氧化水平,包括过氧化氢酶(catalase, CAT)、谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)、脂质过氧化物(lipid peroxide, LPO)、丙二醛、活性氧,验证铁沉积可能通过铁死亡的脂质过氧化代谢调控机制引起DA损伤。结果 与对照组比较,MPTP组运动速率和运动距离明显降低,差异有统计学意义(P<0.01);与MPTP组比较,诺米芬辛组运动速率和运动距离明显升高,差异有统计学意义(P<0.01)。免疫荧光检测显示,与对照组比较,MPTP组DA损伤明显增加,诺米芬辛组DA损伤明显轻于MPTP组。各组CAT水平比较,差异无统计学意义(P>0.05)。与对照组比较,MPTP组铁、LPO和丙二醛水平明显升高,GSH、GPX4水平明显降低,差异有统计学意义(838.18±143.42 vs 478.53±112.58,P<0.05;1.71±0.11 vs 1.48±0.14,P<0.05;4.50±0.64 vs 4.23±0.13,P<0.05;38.93±1.72 vs 45.97±2.32,P<0.05;0.17±0.03 vs 0.39±0.04,P<0.05);与MPTP组比较,诺米芬辛组GSH、GPX4水平明显升高,铁、LPO水平明显降低,差异有统计学意义(40.79±1.02 vs 38.93±1.72,P<0.05;0.26±0.05 vs 0.17±0.03,P<0.05;326.75±110.95 vs 838.18±143.42,P<0.05;1.01±0.27 vs 1.71±0.11,P<0.05)。活性氧流式细胞检测结果显示,对照组、MPTP组及诺米芬辛组活性氧阳性细胞占比分别为直方图:31.6%、46.2%、31.3%,散点图:62.4%、73.0%、65.7%。结论 在MPTP诱导的斑马鱼基础上,PD斑马鱼存在铁死亡。从动物水平阐明铁沉积引起DA损伤与铁死亡脂质过氧化代谢机制有关。展开更多
基金supported by the National Natural Science Foundation of China(No.32471186,No.32071176)the 14th Five-Year-Plan Advantageous and Characteristic Disci-plines(Groups)of Colleges and Universities in Hubei Prov-ince for Exercise and Brain Science from Hubei Provincial Department of Educationthe Leading Talent Program and Innovative Start-Up Foundation from Wuhan Sports University to NC.All figures were created by Figdraw(www.figdraw.com).
文摘Ferroptosis is a programmed cell death,and its mechanism involves multiple metabolic pathways,such as iron and lipid metabolism,and redox homeostasis.Exerkines are important mediators that optimize cellular homeostasis and maintain physiological health during exercise stim-ulation.This article comprehensively examines the mechanisms and regulatory networks for governing ferroptosis and summarizes the impact of exercise and exerkines on ferroptosis under varying load intensities and disease contexts.Notably,despite its significant efficacy and minimal side effects, the therapeutic and prognostic potential of exercise in ferroptosis-related diseases remains largely unexplored.This article,by summarizing recent progresses in the regulation of exerkines-mediated ferroptosis,could further uncover the preventive or alleviative mecha-nisms of some diseases upon exercise interventions,which will be beneficial to design exercise interventional strategies for alleviating disease progression through the regulation of ferroptosis.
文摘目的 在动物水平探讨铁死亡脂质过氧化损伤调控通路与帕金森病(Parkinson's disease, PD)的发病机制。方法 建立PD斑马鱼动物模型,取受精后48 h斑马鱼胚胎为对照组(n=100),200μmol/L的1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP)为MPTP组(n=100),200μmol/L的MPTP+1.5μg/ml诺米芬辛为诺米芬辛组(n=100)。对受精后5 d斑马鱼进行行为学分析(检测运动能力、运动速率及运动距离);免疫荧光检测斑马鱼脑内α突触核蛋白和酪氨酸羟化酶表达,评估多巴胺能神经元(dopaminergic neurons, DA)活性;检测铁、谷胱甘肽(glutathione, GSH)及脂质过氧化水平,包括过氧化氢酶(catalase, CAT)、谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)、脂质过氧化物(lipid peroxide, LPO)、丙二醛、活性氧,验证铁沉积可能通过铁死亡的脂质过氧化代谢调控机制引起DA损伤。结果 与对照组比较,MPTP组运动速率和运动距离明显降低,差异有统计学意义(P<0.01);与MPTP组比较,诺米芬辛组运动速率和运动距离明显升高,差异有统计学意义(P<0.01)。免疫荧光检测显示,与对照组比较,MPTP组DA损伤明显增加,诺米芬辛组DA损伤明显轻于MPTP组。各组CAT水平比较,差异无统计学意义(P>0.05)。与对照组比较,MPTP组铁、LPO和丙二醛水平明显升高,GSH、GPX4水平明显降低,差异有统计学意义(838.18±143.42 vs 478.53±112.58,P<0.05;1.71±0.11 vs 1.48±0.14,P<0.05;4.50±0.64 vs 4.23±0.13,P<0.05;38.93±1.72 vs 45.97±2.32,P<0.05;0.17±0.03 vs 0.39±0.04,P<0.05);与MPTP组比较,诺米芬辛组GSH、GPX4水平明显升高,铁、LPO水平明显降低,差异有统计学意义(40.79±1.02 vs 38.93±1.72,P<0.05;0.26±0.05 vs 0.17±0.03,P<0.05;326.75±110.95 vs 838.18±143.42,P<0.05;1.01±0.27 vs 1.71±0.11,P<0.05)。活性氧流式细胞检测结果显示,对照组、MPTP组及诺米芬辛组活性氧阳性细胞占比分别为直方图:31.6%、46.2%、31.3%,散点图:62.4%、73.0%、65.7%。结论 在MPTP诱导的斑马鱼基础上,PD斑马鱼存在铁死亡。从动物水平阐明铁沉积引起DA损伤与铁死亡脂质过氧化代谢机制有关。
