Objective: Mitochondrial impairment in the skeletal muscle contributes to useless of limbs in spleen qi deficiency;however the genesis of such impairment is not clear. Herein, PTEN-induced putative kinase 1 (PINK1)-Pa...Objective: Mitochondrial impairment in the skeletal muscle contributes to useless of limbs in spleen qi deficiency;however the genesis of such impairment is not clear. Herein, PTEN-induced putative kinase 1 (PINK1)-Parkin pathway and mitophagy were studied to explore the machinery of mitochondrial impairment. Methods: 16 male SD rats were randomly divided in the control group and spleen qi deficiency group (model group);transmission electron microscope was used to observe mitochondrial morphology;mitochondrial oxidative phosphorylation was assessed by testing mitochondrial membrane potential (MMP) and levels of ATP and ROS;western blot was used to analyze expressions of PINK1, Parkin, microtubule-associated protein 1 light chain 3-II (LC3-II) and p62. Results: Compared with those in the control group, mitochondria became small, less and scattered, MMP and the ATP level were reduced, the ROS level was elevated, PINK1 expression was decreased, p62 expression was increased, but Parkin and LC3-II expressions were not altered, in the model group. Conclusions: Suppression of mitophagy might be related to the mitochondrial damage in the skeletal muscle when spleen qi deficiency develops.展开更多
Hunter-gatherer communities in the American Southeast reached an apogee of social and political complexity in the period between ca. 4200 and 3000 cal yr BP. In the lower Mississippi Valley(LMV) the Poverty Point cult...Hunter-gatherer communities in the American Southeast reached an apogee of social and political complexity in the period between ca. 4200 and 3000 cal yr BP. In the lower Mississippi Valley(LMV) the Poverty Point culture defined this period of socio-political elaboration. However, following a significant period of climate change that led to exceptional flooding and a major reorganization of the course of the Mississippi River, this culture collapsed beginning ca. 3300–3200 cal yr BP and the LMV was abandoned for the subsequent 500 years. In this study, we use data from the Jaketown site in the Yazoo Basin of west-central Mississippi to refine the chronology of the climate event that caused the collapse of the Poverty Point culture. A large flood buried Poverty Point-era occupation deposits at Jaketown around 3310 cal yr BP. Lateral migration of the Mississippi River during flooding led to inundation of the Yazoo Basin and re-occupation of ancient river courses. A coarse sand stratum topped by a more than a meter-thick fining upward sediment package marks a crevasse deposit caused by a rupture of the natural levee at Jaketown. This levee breach was part of a larger pattern of erratic flooding throughout the LMV and is associated with major landscape evolution and the abandonment of Poverty Point sites within the valley. Early Woodland peoples re-colonized the crevasse surface after ca. 2780 cal yr BP. Following this event, the Jaketown site and the eastern Yazoo Basin witnessed a period of landscape stability that lasts to this day. These archaeological data demonstrate how climate change and natural disasters can lead to socio-political dissolution and reorganization even in relatively small-scale hunter-gatherer populations.展开更多
OBJECTIVE:To investigate the efficacy of Sijunzi decoction(四君子汤)on limb weakness in a rat model of spleen Qi deficiency(SQD),and to study its effect on mitophagy in skeletal muscle through adenosine monophosphate-...OBJECTIVE:To investigate the efficacy of Sijunzi decoction(四君子汤)on limb weakness in a rat model of spleen Qi deficiency(SQD),and to study its effect on mitophagy in skeletal muscle through adenosine monophosphate-activated protein kinase(AMPK)/unc-51 like autophagy activating kinase 1(ULK1)signaling.METHODS:SQD model rats were produced by fasting combined with forced swimming method for15 d.After model assessment,rats were randomly divided into four groups of 10[low/middle/high(L/M/H)Sijunzi decoction dose groups and a normal saline(S)group].Limb holding power(HP)and body mass(BM)were measured after 2 weeks of treatment.Following euthanasia,quadriceps femoris were dissected and myofiber and mitochondrial morphology were observed by transmission electron microscopy(TEM).Mitochondrial membrane potential(MMP),adenosine triphosphatase(ATP)and reactive oxygen species(ROS)levels were determined using colorimetric methods,and immunoblot analysis of Microtubule-associated protein light chain 3(LC3)and Sequestosome 1(p62)was performed to monitor mitophagy and AMPK/ULK1 signaling.RESULTS:Compared with control(C)group rats,in the S group,HP was reduced,the myofiber Z line was disordered,mitochondria were scattered,and numerous vacuoles and mitophagy were observed.MMP and ATP levels were reduced,ROS levels were elevated,and LC3B expression,and p-AMPKα(Thr172)/AMPKα,p-ULK1(Ser555)/ULK1,and p-Raptor(Ser792)/Raptor ratios were increased,while p62 expression and p-mT OR(Ser2448)/mT OR and p-ULK1(Ser757)/ULK1 ratios were decreased.After treatment,compared with the S group,HP was improved in M and H groups but not in the L group.Mitophagy was reduced in M,H and L groups but the Z line was disordered and vacuolization remained in the L group.ATP levels were elevated in M,H and L groups,and MMPs were elevated in M and H groups but not in the L group.ROS levels were decreased in M,H and L groups,as were LC3B expression and p-Raptor(Ser792)/Raptor ratios,while p62 expression and p-mT OR(Ser2448)/mT OR and p-ULK1(Ser757)/ULK1 ratios were increased in M and H groups but not in the L group.p-AMPKα(Thr172)/AMPKαand p-ULK1(Ser555)/ULK1 ratios were decreased in M,H and L groups.CONCLUSIONS:Sijunzi decoction improved HP,possibly by inhibiting mitophagy via suppression of AMPK/ULK1 signaling.This restored mitochondrial morphology and improved oxidative phosphorylation,which contributed to recovery of limb weakness in SQD model rats.展开更多
文摘Objective: Mitochondrial impairment in the skeletal muscle contributes to useless of limbs in spleen qi deficiency;however the genesis of such impairment is not clear. Herein, PTEN-induced putative kinase 1 (PINK1)-Parkin pathway and mitophagy were studied to explore the machinery of mitochondrial impairment. Methods: 16 male SD rats were randomly divided in the control group and spleen qi deficiency group (model group);transmission electron microscope was used to observe mitochondrial morphology;mitochondrial oxidative phosphorylation was assessed by testing mitochondrial membrane potential (MMP) and levels of ATP and ROS;western blot was used to analyze expressions of PINK1, Parkin, microtubule-associated protein 1 light chain 3-II (LC3-II) and p62. Results: Compared with those in the control group, mitochondria became small, less and scattered, MMP and the ATP level were reduced, the ROS level was elevated, PINK1 expression was decreased, p62 expression was increased, but Parkin and LC3-II expressions were not altered, in the model group. Conclusions: Suppression of mitophagy might be related to the mitochondrial damage in the skeletal muscle when spleen qi deficiency develops.
基金supported by the U.S. National Science Foundation (Grant No. #0827097) with additional support from the Edward S. and Tedi Macias fund at Washington University in St. Louis
文摘Hunter-gatherer communities in the American Southeast reached an apogee of social and political complexity in the period between ca. 4200 and 3000 cal yr BP. In the lower Mississippi Valley(LMV) the Poverty Point culture defined this period of socio-political elaboration. However, following a significant period of climate change that led to exceptional flooding and a major reorganization of the course of the Mississippi River, this culture collapsed beginning ca. 3300–3200 cal yr BP and the LMV was abandoned for the subsequent 500 years. In this study, we use data from the Jaketown site in the Yazoo Basin of west-central Mississippi to refine the chronology of the climate event that caused the collapse of the Poverty Point culture. A large flood buried Poverty Point-era occupation deposits at Jaketown around 3310 cal yr BP. Lateral migration of the Mississippi River during flooding led to inundation of the Yazoo Basin and re-occupation of ancient river courses. A coarse sand stratum topped by a more than a meter-thick fining upward sediment package marks a crevasse deposit caused by a rupture of the natural levee at Jaketown. This levee breach was part of a larger pattern of erratic flooding throughout the LMV and is associated with major landscape evolution and the abandonment of Poverty Point sites within the valley. Early Woodland peoples re-colonized the crevasse surface after ca. 2780 cal yr BP. Following this event, the Jaketown site and the eastern Yazoo Basin witnessed a period of landscape stability that lasts to this day. These archaeological data demonstrate how climate change and natural disasters can lead to socio-political dissolution and reorganization even in relatively small-scale hunter-gatherer populations.
基金Supported by National Natural Science Foundation of China:the Investigation of Sijunzi Decoction Treating Limb Useless on UPR-Mitophagy-Apoptosis Mechanism in Spleen-Qi Deficiency(No.81803986)Education Department of Liaoning:the Investigation of Yiqi Jianpi Decoction Combined with Metformin Treating Diabetic Muscle Atrophy on UPSMitophagy Through PGC-1α/FOXO3 axis(No.L201940)。
文摘OBJECTIVE:To investigate the efficacy of Sijunzi decoction(四君子汤)on limb weakness in a rat model of spleen Qi deficiency(SQD),and to study its effect on mitophagy in skeletal muscle through adenosine monophosphate-activated protein kinase(AMPK)/unc-51 like autophagy activating kinase 1(ULK1)signaling.METHODS:SQD model rats were produced by fasting combined with forced swimming method for15 d.After model assessment,rats were randomly divided into four groups of 10[low/middle/high(L/M/H)Sijunzi decoction dose groups and a normal saline(S)group].Limb holding power(HP)and body mass(BM)were measured after 2 weeks of treatment.Following euthanasia,quadriceps femoris were dissected and myofiber and mitochondrial morphology were observed by transmission electron microscopy(TEM).Mitochondrial membrane potential(MMP),adenosine triphosphatase(ATP)and reactive oxygen species(ROS)levels were determined using colorimetric methods,and immunoblot analysis of Microtubule-associated protein light chain 3(LC3)and Sequestosome 1(p62)was performed to monitor mitophagy and AMPK/ULK1 signaling.RESULTS:Compared with control(C)group rats,in the S group,HP was reduced,the myofiber Z line was disordered,mitochondria were scattered,and numerous vacuoles and mitophagy were observed.MMP and ATP levels were reduced,ROS levels were elevated,and LC3B expression,and p-AMPKα(Thr172)/AMPKα,p-ULK1(Ser555)/ULK1,and p-Raptor(Ser792)/Raptor ratios were increased,while p62 expression and p-mT OR(Ser2448)/mT OR and p-ULK1(Ser757)/ULK1 ratios were decreased.After treatment,compared with the S group,HP was improved in M and H groups but not in the L group.Mitophagy was reduced in M,H and L groups but the Z line was disordered and vacuolization remained in the L group.ATP levels were elevated in M,H and L groups,and MMPs were elevated in M and H groups but not in the L group.ROS levels were decreased in M,H and L groups,as were LC3B expression and p-Raptor(Ser792)/Raptor ratios,while p62 expression and p-mT OR(Ser2448)/mT OR and p-ULK1(Ser757)/ULK1 ratios were increased in M and H groups but not in the L group.p-AMPKα(Thr172)/AMPKαand p-ULK1(Ser555)/ULK1 ratios were decreased in M,H and L groups.CONCLUSIONS:Sijunzi decoction improved HP,possibly by inhibiting mitophagy via suppression of AMPK/ULK1 signaling.This restored mitochondrial morphology and improved oxidative phosphorylation,which contributed to recovery of limb weakness in SQD model rats.
