目的探讨肌萎缩性侧索硬化症(ALS)转基因鼠脊髓内铁转运相关蛋白表达变化与铁稳态失衡的关联。方法选取h SOD1G93A转基因鼠(ALS鼠)和同窝野生型鼠(WT鼠),分别于生后70、95和122 d分离脊髓,每时间点每组各9只实验动物。Western blotting...目的探讨肌萎缩性侧索硬化症(ALS)转基因鼠脊髓内铁转运相关蛋白表达变化与铁稳态失衡的关联。方法选取h SOD1G93A转基因鼠(ALS鼠)和同窝野生型鼠(WT鼠),分别于生后70、95和122 d分离脊髓,每时间点每组各9只实验动物。Western blotting检测脊髓组织内铁转运蛋白二价金属转运蛋白-1(DMT1)、铁转运蛋白-1(FPN1)及调节蛋白铁调节蛋白-1(IRP1)的表达;免疫荧光双重标记检测脊髓腰段前角内细胞共定位情况。结果Western blotting显示,与WT鼠比较,各时间点ALS鼠脊髓内DMT1表达均显著降低(P<0.05,P<0.01);70 d FPN1表达升高(P<0.05),95 d和122 d表达下降(P<0.01);95 d、122 d IRP1表达降低(P<0.01)。免疫荧光双重标记显示,在70 d WT鼠和ALS鼠腰段脊髓中DMT1主要与β-微管蛋白Ⅲ(β-tubulinⅢ)共表达。与WT组相比,95 d ALS鼠脊髓腰段前角神经元内DMT1免疫反应强,而FPN1荧光强度减弱。随疾病进展,DMT1、FPN1与反应性胶质细胞共定位表达增多。IRP1随疾病进展表达强度降低。结论随ALS病程进展,发病早期神经元铁转入增加,转出减少,反应性神经胶质细胞铁转运活性增强,参与局部铁稳态失衡及脊髓前角运动神经元进行性丢失。IRP1表达降低,部分参与局部铁代谢调节。展开更多
Environmental pollution has become one of the greatest problems in the world, and the concerns about environmental pollutants released by human activities from agriculture and industrial production have been continuou...Environmental pollution has become one of the greatest problems in the world, and the concerns about environmental pollutants released by human activities from agriculture and industrial production have been continuously increasing. Although intense efforts have been made to understand the health effects of environmental pollutants, most studies have only focused on direct toxic effects and failed to simultaneously evaluate the long-term adaptive, compensatory and secondary impacts on health. Burgeoning evidence suggests that environmental pollutants may directly or indirectly give rise to disordered element homeostasis, such as for iron. It is crucially important to maintain concerted cellular and systemic iron metabolism. Otherwise, disordered iron metabolism would lead to cytotoxicity and increased risk for various diseases, including cancers. Thus, study on the effects of environmental pollutants upon iron homeostasis is urgently needed. In this review, we recapitulate the available findings on the direct or indirect impacts of environmental pollutants, including persistent organic pollutants（POPs）, heavy metals and pesticides, on iron homeostasis and associated adverse health problems. In view of the unanswered questions, more efforts are warranted to investigate the disruptive effects of environmental pollutants on iron homeostasis and consequent toxicities.展开更多
Among the numerous health conditions environmental pollutants can cause, chronic exposure to pollutants including persistent organic pollutants（POPs） and heavy metals has been shown to disturb a specific biological ...Among the numerous health conditions environmental pollutants can cause, chronic exposure to pollutants including persistent organic pollutants（POPs） and heavy metals has been shown to disturb a specific biological homeostatic process, the iron metabolism in human body. Disorders of iron metabolism are among the common diseases of humans and encompass a broad spectrum of diseases with different clinical manifestations, ranging from anemia to iron overload, and possibly to neurodegenerative diseases and cancer.Hepcidin–ferroportin（FPN） signaling is one of the key mechanisms responsible for iron supply, utilization, recycling, and storage, and recent studies demonstrated that exposure to environmental pollutants including POPs and heavy metals could lead to disruption of the hepcidin–FPN axis along with disordered systemic iron homeostasis and diseases. This article introduces and highlights the accompanying review article by Drs. Xu and Liu in this journal, which elaborates in detail the adverse effects of environmental pollutants on iron metabolism, and the mechanisms responsible for these toxicological outcomes. It also points out the knowledge gaps still existing in this subject matter. Research that will fill these gaps will improve our understanding of the issue and provide useful information to prevent or treat diseases induced by environmental pollutants.展开更多
Changes in the global environment such as ocean acidification （OA） may interact with anthropogenic pollutants including trace metals threatening the integrity of marine ecosystems. We analyze recent studies on the i...Changes in the global environment such as ocean acidification （OA） may interact with anthropogenic pollutants including trace metals threatening the integrity of marine ecosystems. We analyze recent studies on the interactive effects of OA and trace metals on marine organisms with a focus on the physiological basis of these interactions. Our analysis shows that the responses to elevated CO2 and metals are strongly dependent on the species, developmental stage, metal biochemistry and the degree of environmental hypercapnia, and cannot be directly predicted from the CO2-induced changes in metal solubility and speciation. The key physiological functions affected by both the OA and trace metal exposures involve acid-base regulation, pro- tein turnover and mitochondrial bioenergetics, reflecting the sensitivity of the underlying molecular and cellular pathways to CO2 and metals. Physiological interactions between elevated CO2 and metals may impact the organisms＇ capacity to maintain ac- id-base homeostasis and reduce the amount of energy available for fitness-related functions such as growth, development and re- production thereby affecting survival and performance of estuarine populations. Environmental hypercapnia may also affect the marine food webs by altering predator-prey interactions and the trophic transfer of metals in the food chain. However, our under- standing of the degree to which these effects can impact the function and integrity of marine ecosystems is limited due the scar- city of the published research and its bias towards certain taxonomic groups. Future research priorities should include studies of metal x Pco2 interactions focusing on critical physiological functions （including acid-base, protein and energy homeostasis） in a greater range of ecologically and economically important marine species, as well as including the field populations naturally ex- posed （and potentially adapted） to different levels of metals and CO2 in their environments [Current Zoology 61 （4）： 653-668, 2015].展开更多
Iron (Fe) is an essential micronutrient that affects the growth and development of plants because it participates as a cofactor in numerous physiological and biochemical reactions. As a transition metal, Fe is redoxac...Iron (Fe) is an essential micronutrient that affects the growth and development of plants because it participates as a cofactor in numerous physiological and biochemical reactions. As a transition metal, Fe is redoxactive. Fe often exists in soil in the form of insoluble ferric hydroxides that are not bioavailable to plants.Plants have developed sophisticated mechanisms to ensure an adequate supply of Fe in a fluctuating environment. Plants can sense Fe status and modulate the transcription of Fe uptake-associated genes, finallycontrolling Fe uptake from soil to root. There is a critical need to understand the molecular mechanisms bywhich plants maintain Fe homeostasis in response to Fe fluctuations. This review focuses on recentadvances in elucidating the functions of Fe signaling components. Taking Arabidopsis thaliana and Oryzasativa as examples, this review begins by discussing the Fe acquisition systems that control Fe uptake fromsoil, the major components that regulate Fe uptake systems, and the perception of Fe status. Future explorations of Fe signal transduction will pave the way for understanding the regulatory mechanisms that underlie the maintenance of plant Fe homeostasis.展开更多
文摘目的探讨肌萎缩性侧索硬化症(ALS)转基因鼠脊髓内铁转运相关蛋白表达变化与铁稳态失衡的关联。方法选取h SOD1G93A转基因鼠(ALS鼠)和同窝野生型鼠(WT鼠),分别于生后70、95和122 d分离脊髓,每时间点每组各9只实验动物。Western blotting检测脊髓组织内铁转运蛋白二价金属转运蛋白-1(DMT1)、铁转运蛋白-1(FPN1)及调节蛋白铁调节蛋白-1(IRP1)的表达;免疫荧光双重标记检测脊髓腰段前角内细胞共定位情况。结果Western blotting显示,与WT鼠比较,各时间点ALS鼠脊髓内DMT1表达均显著降低(P<0.05,P<0.01);70 d FPN1表达升高(P<0.05),95 d和122 d表达下降(P<0.01);95 d、122 d IRP1表达降低(P<0.01)。免疫荧光双重标记显示,在70 d WT鼠和ALS鼠腰段脊髓中DMT1主要与β-微管蛋白Ⅲ(β-tubulinⅢ)共表达。与WT组相比,95 d ALS鼠脊髓腰段前角神经元内DMT1免疫反应强,而FPN1荧光强度减弱。随疾病进展,DMT1、FPN1与反应性胶质细胞共定位表达增多。IRP1随疾病进展表达强度降低。结论随ALS病程进展,发病早期神经元铁转入增加,转出减少,反应性神经胶质细胞铁转运活性增强,参与局部铁稳态失衡及脊髓前角运动神经元进行性丢失。IRP1表达降低,部分参与局部铁代谢调节。
基金supported by a grant under the national " 973 " program (No: 2014CB932000)the Strategic Priority Research Program of the Chinese Academy of Sciences (No.XDB14000000)the National Natural Science Foundation of China (Nos: 21425731, 21377159, 21177151, and 21321004)
文摘Environmental pollution has become one of the greatest problems in the world, and the concerns about environmental pollutants released by human activities from agriculture and industrial production have been continuously increasing. Although intense efforts have been made to understand the health effects of environmental pollutants, most studies have only focused on direct toxic effects and failed to simultaneously evaluate the long-term adaptive, compensatory and secondary impacts on health. Burgeoning evidence suggests that environmental pollutants may directly or indirectly give rise to disordered element homeostasis, such as for iron. It is crucially important to maintain concerted cellular and systemic iron metabolism. Otherwise, disordered iron metabolism would lead to cytotoxicity and increased risk for various diseases, including cancers. Thus, study on the effects of environmental pollutants upon iron homeostasis is urgently needed. In this review, we recapitulate the available findings on the direct or indirect impacts of environmental pollutants, including persistent organic pollutants（POPs）, heavy metals and pesticides, on iron homeostasis and associated adverse health problems. In view of the unanswered questions, more efforts are warranted to investigate the disruptive effects of environmental pollutants on iron homeostasis and consequent toxicities.
文摘Among the numerous health conditions environmental pollutants can cause, chronic exposure to pollutants including persistent organic pollutants（POPs） and heavy metals has been shown to disturb a specific biological homeostatic process, the iron metabolism in human body. Disorders of iron metabolism are among the common diseases of humans and encompass a broad spectrum of diseases with different clinical manifestations, ranging from anemia to iron overload, and possibly to neurodegenerative diseases and cancer.Hepcidin–ferroportin（FPN） signaling is one of the key mechanisms responsible for iron supply, utilization, recycling, and storage, and recent studies demonstrated that exposure to environmental pollutants including POPs and heavy metals could lead to disruption of the hepcidin–FPN axis along with disordered systemic iron homeostasis and diseases. This article introduces and highlights the accompanying review article by Drs. Xu and Liu in this journal, which elaborates in detail the adverse effects of environmental pollutants on iron metabolism, and the mechanisms responsible for these toxicological outcomes. It also points out the knowledge gaps still existing in this subject matter. Research that will fill these gaps will improve our understanding of the issue and provide useful information to prevent or treat diseases induced by environmental pollutants.
基金This work was in part supported by funds provided by the National Science Foundation award I0S-095107 and UNC Charlotte＇s Faculty Research Grant to I.M.S.
文摘Changes in the global environment such as ocean acidification （OA） may interact with anthropogenic pollutants including trace metals threatening the integrity of marine ecosystems. We analyze recent studies on the interactive effects of OA and trace metals on marine organisms with a focus on the physiological basis of these interactions. Our analysis shows that the responses to elevated CO2 and metals are strongly dependent on the species, developmental stage, metal biochemistry and the degree of environmental hypercapnia, and cannot be directly predicted from the CO2-induced changes in metal solubility and speciation. The key physiological functions affected by both the OA and trace metal exposures involve acid-base regulation, pro- tein turnover and mitochondrial bioenergetics, reflecting the sensitivity of the underlying molecular and cellular pathways to CO2 and metals. Physiological interactions between elevated CO2 and metals may impact the organisms＇ capacity to maintain ac- id-base homeostasis and reduce the amount of energy available for fitness-related functions such as growth, development and re- production thereby affecting survival and performance of estuarine populations. Environmental hypercapnia may also affect the marine food webs by altering predator-prey interactions and the trophic transfer of metals in the food chain. However, our under- standing of the degree to which these effects can impact the function and integrity of marine ecosystems is limited due the scar- city of the published research and its bias towards certain taxonomic groups. Future research priorities should include studies of metal x Pco2 interactions focusing on critical physiological functions （including acid-base, protein and energy homeostasis） in a greater range of ecologically and economically important marine species, as well as including the field populations naturally ex- posed （and potentially adapted） to different levels of metals and CO2 in their environments [Current Zoology 61 （4）： 653-668, 2015].
基金This work was supported by the National Natural Science Foundation of China(32070278)the Youth Talent Support Program of Yunnan Province(YNWR-QNBJ-2018-134).No conflict of interest declared.
文摘Iron (Fe) is an essential micronutrient that affects the growth and development of plants because it participates as a cofactor in numerous physiological and biochemical reactions. As a transition metal, Fe is redoxactive. Fe often exists in soil in the form of insoluble ferric hydroxides that are not bioavailable to plants.Plants have developed sophisticated mechanisms to ensure an adequate supply of Fe in a fluctuating environment. Plants can sense Fe status and modulate the transcription of Fe uptake-associated genes, finallycontrolling Fe uptake from soil to root. There is a critical need to understand the molecular mechanisms bywhich plants maintain Fe homeostasis in response to Fe fluctuations. This review focuses on recentadvances in elucidating the functions of Fe signaling components. Taking Arabidopsis thaliana and Oryzasativa as examples, this review begins by discussing the Fe acquisition systems that control Fe uptake fromsoil, the major components that regulate Fe uptake systems, and the perception of Fe status. Future explorations of Fe signal transduction will pave the way for understanding the regulatory mechanisms that underlie the maintenance of plant Fe homeostasis.
