目的观察线粒体未折叠蛋白反应(mitochondrial unfolded protein response,mtUPR)在氯化锂-匹鲁卡品(pilocarpine,PILO)致痫大鼠海马神经中的变化及线粒体特异性抗氧化剂Mito-TEMPO对其影响。方法采用PILO诱导癫痫大鼠模型,并进一步采...目的观察线粒体未折叠蛋白反应(mitochondrial unfolded protein response,mtUPR)在氯化锂-匹鲁卡品(pilocarpine,PILO)致痫大鼠海马神经中的变化及线粒体特异性抗氧化剂Mito-TEMPO对其影响。方法采用PILO诱导癫痫大鼠模型,并进一步采用线粒体特异性抗氧化剂Mito-TEMPO进行干预;将成年雄性Wistar大鼠随机分为空白对照组(CON组)、致痫组(PILO组)、Mito-TEMPO组和PILO+Mito-TEMPO组;采用Nissl染色观察海马神经元损伤,电子透射显微镜观察线粒体超微结构,活性氧荧光探针(DCFDA)检测线粒体ROS生成,Rhodamine123染色法检测线粒体膜电位变化,Western blot法检测线粒体热休克蛋白HSP60、蛋白酶LONP1、线粒体蛋白酶CLpP的表达。结果(1)与CON组相比,PILO组海马神经线粒体超微结构破坏严重,线粒体ROS生成增多,线粒体膜电位降低;(2)与CON组相比,PILO组海马神经HSP60、LONP1和CLpP表达增加;(3)与PILO组相比,PILO+Mito-TEMPO组线粒体超微结构破坏减轻,线粒体ROS生成明显减少,线粒体膜电位增高;(4)与PILO组相比,PILO+Mito-TEMPO组海马神经HSP60、LONP1和CLpP表达降低。结论mtUPR在癫痫海马神经损伤中明显激活,Mito-TEMPO可能通过调控mtUPR对癫痫海马线粒体损伤发挥保护作用。展开更多
对12月龄SD大鼠给予L-苹果酸30d后,采用含有SYBR Green I的Real Time RT-PCR法,对肝脏和心脏线粒体苹果酸天冬氨酸穿梭中的两种转运蛋白(天冬氨酸谷氨酸转运蛋白(AGC)与α-酮戊二酸苹果酸转运蛋白(OMC))以及两种抗氧化酶(过氧化氢酶(CAT...对12月龄SD大鼠给予L-苹果酸30d后,采用含有SYBR Green I的Real Time RT-PCR法,对肝脏和心脏线粒体苹果酸天冬氨酸穿梭中的两种转运蛋白(天冬氨酸谷氨酸转运蛋白(AGC)与α-酮戊二酸苹果酸转运蛋白(OMC))以及两种抗氧化酶(过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-Px))的基因表达进行检测,以研究L-苹果酸增强线粒体抗氧化作用的分子生物学机制。结果表明:苹果酸组中大鼠心肌细胞AGC、OMC、CAT、GSH-Px的mRNA表达量分别是空白对照组的1.25、1.39、1.12、1.01倍。苹果酸组中大鼠肝脏细胞AGC、OMC、CAT、GSH-Px的mRNA表达量分别是空白对照组的1.33、1.02、1.25、0.94倍。由此推测,L-苹果酸可能通过促进苹果酸天冬氨酸穿梭蛋白以及抗氧化酶的基因表达,实现提高线粒体的抗氧化作用。展开更多
氧化应激是川崎病发病机制之一,活性氧的过量产生将导致氧化应激,控制活性氧的产生将有助于减轻氧化应激的程度,有可能改善川崎病患儿预后,因此抗氧化剂可以作为川崎病急性期的辅助疗法,特别是针对特定细胞器的靶向抗氧化剂有望成为川...氧化应激是川崎病发病机制之一,活性氧的过量产生将导致氧化应激,控制活性氧的产生将有助于减轻氧化应激的程度,有可能改善川崎病患儿预后,因此抗氧化剂可以作为川崎病急性期的辅助疗法,特别是针对特定细胞器的靶向抗氧化剂有望成为川崎病的新型治疗措施。本文将对活性氧的产生和在川崎病中产生的病理作用,以及抗氧化剂目前的研究进展进行讨论。Oxidative stress is one of the pathogenesis of Kawasaki disease. Excessive production of reactive oxygen species will lead to oxidative stress. Controlling the production of reactive oxygen species will help to reduce the degree of oxidative stress and may improve the prognosis of children with Kawasaki disease. Therefore, antioxidants can be used as an adjuvant therapy for the acute phase of Kawasaki disease, especially for specific organelles. Targeted antioxidants are expected to become a new treatment for Kawasaki disease. This article will discuss the production of reactive oxygen species and the pathological effects in Kawasaki disease, as well as the current research progress of antioxidants.展开更多
[Objective] This study aimed to investigate the protective effects of aqueous extract of Eucommia ulmiodes Oliver leaves （AEO） on liver mitochondrial injury induced by free radicals. [Method] MDA content was determi...[Objective] This study aimed to investigate the protective effects of aqueous extract of Eucommia ulmiodes Oliver leaves （AEO） on liver mitochondrial injury induced by free radicals. [Method] MDA content was determined by thiobarbituric acid colorimetric method; mitochondrial swelling degree was determined by spectrophotometry; the superoxide anion radical scavenging ability was determined using reduced coenzyme I-tetrazolium-phenazine methosulfate as the superoxide anion generation system. Mice were hypodermically injected in the back and neck with D- galactose, after 50 d, the effects of AEO on the activities of superoxide dismutase （SOD）, glutathione peroxidase （GSH-Px） and anti-hydroxyl radicals in mouse liver were determined using kits. [Result] AEO can efficiently reduce the liver injury and inhibit mitochondrial swelling induced by Fe2＋-L-Cys, which can also scavenge superoxide anion and improve the activities of antioxidant enzymes. [Conclusion] This study provided scientific basis for the development and application of AEO resources.展开更多
Mitochondrial redox metabolism has long been recognized as being central to the effects of aging and the development of age-related pathologies in the major oxidative organs. Consistent evidence has shown that exercis...Mitochondrial redox metabolism has long been recognized as being central to the effects of aging and the development of age-related pathologies in the major oxidative organs. Consistent evidence has shown that exercise is able to retard the onset and impede the progression of aging by modifying mitochondrial oxidant--antioxidant homeostasis. Here we provide a broad overview of the research evidence showing the relationship between mitochondrial redox metabolism, aging and exercise. We address part aspects of mitochondrial reactive oxygen species （ROS） metabolism, from superoxide production to ROS detoxification, especially antioxidant enzymes and uncoupling protein. Furthermore, we describe mitochondrial remodeling response to aging and exercise, which is accompanied by bioenergetics and redox regulation. In addition, potential mechanisms for redox signaling involved in mitochondrial remodeling and redox metabolism regulation are also reviewed.展开更多
Objective: To observe the neuroprotective mechanism of water extract of Fomito^p^is Pinicola on MPP+ induced apoptosis of mesencephala dopaminergic cells in vitro. Methods: The antioxidant activity of fungi was determ...Objective: To observe the neuroprotective mechanism of water extract of Fomito^p^is Pinicola on MPP+ induced apoptosis of mesencephala dopaminergic cells in vitro. Methods: The antioxidant activity of fungi was determined by FRAP method. The anti-inflammatory activity of the fungi was detected by LPS-induced NO release method. Mesencephalic dopaminergic neurons were labeled by TH staining to observe the survival of THir neurons. Results: In the anti-oxidant activity assay, the Trolox equivalent anti-oxidant capacity (TEAC) of water extract of Fomitopsis Pinicola was determined to be ( 165.80±7.13 )μmol Trolox/g extract. Water extracts o f Fomitopsis Pinicola treatment(100, 5 0 ,2 5 , 12.5^g/ml) decreased NO formation significantly. MPP+ induced significant chromatin condensation in the nuclei of mesencephala dopaminergic neurons with nuclear lysis, the mitochondrial membrane potential decreased remarkably, and ROS production increased significantly. Compared with the MPP+ control group, the morphological changes of cell nuclei after apoptosis was reversed by water extract of Fomitopsis Pinicola. Water extract of Fomitopsis Pinicola treatment (50,25,12.5^g/ml) dramatically increased relative mitochondrial membrane potential compared with MPP+ control respectively. Compared with the MPP+ control, water extract of Fomitopsis Pinicola treatment (50, 25^g/ml) significantly decreased relative ROS formation respectively. Conclusions: Water extract of Fomitopsis Pinicola showed significant neuroprotective effect on mesencephala dopaminergic cells induced by MPP+. The water extract of Fomitopsis Pinicola showed antioxidant and anti-inflammatory activities. The mechanism of neuroprotective effect of water extract of Fomitopsis Pinicola may be related to inhibitory on mitochondrial oxidative stress.展开更多
Resveratrol(3,5,4’-trihydroxystilbene,RSV) has been widely used in mammalian cells,but whether it can be used during freezing boar semen is still unknown.The effects of RSV treatment during boar semen freezing on its...Resveratrol(3,5,4’-trihydroxystilbene,RSV) has been widely used in mammalian cells,but whether it can be used during freezing boar semen is still unknown.The effects of RSV treatment during boar semen freezing on its anti-freezing ability,apoptosis,and possible apoptotic pathways were observed in this study.Sperm motility,mitochondrial membrane potential(ΔΨm),adenosine triphosphate(ATP) content,terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick-end labeling(TUNEL)-positive apoptotic state,and messenger RNA(mRNA) expression levels of apoptotic genes involved in different apoptotic pathways after freezing with or without RSV treatment were tested.The results showed that:(1) Compared with fresh sperm,the motility,normal acrosome rate,and plasma membrane integrity rate of frozen boar sperm decreased significantly(P<0.05),and RSV did not significantly increase the sperm motility(0.44 vs.0.40,P>0.05),but it did significantly improve the normal acrosome rate(57.65% vs.47.00%,P<0.05) and plasma membrane integrity rate(46.67% vs.38.85%,P<0.05).(2) After freezing,most boar sperm showed low mitochondrial ΔΨm.RSV treatment could increase the rate of high mitochondrial ΔΨm of boar sperm.(3) RSV treatment significantly decreased reactive oxygen species(ROS) levels(58.65% vs.88.41%,P<0.05)and increased the ATP content(0.49 μmol/L vs.0.25 μmol/L,P<0.05) of boar sperm during freezing.(4) The apoptotic rate of the freezing group(80.41%) with TUNEL detection increased significantly compared to the fresh group(9.70%,P<0.05),and RSV treatment greatly decreased the apoptotic rate(68.32%,P<0.05).(5) Real-time polymerase chain reaction(RT-PCR) showed that not only the genes from the death receptor-mediated apoptotic pathway(tumor necrosis factor-α(TNF-α),Fas ligand(FasL),and Caspase-8),but also the genes from the mitochondria-mediated apoptotic pathway(manganese superoxide dismutase(MnSOD),B-cell lymphoma 2(Bcl-2),Bcl-2-associated X protein(Bax),and Caspase-9) were both significantly changed after freezing.RSV treatment during freezing greatly changed their expression levels.Although RSV treatment during boar semen freezing did not significantly increase motility after thawing,it still played an efficient antioxidant role,which could enhance the mitochondrial function and decrease the apoptotic level induced by both the death receptor-and mitochondria-mediated apoptotic pathways.展开更多
The organosulfur compound sulforaphane(SFN;C6H11NOS2) is a potent cytoprotective agent promoting antioxidant, anti-inflammatory, antiglycative, and antimicrobial effects in in vitro and in vivo experimental models. Mi...The organosulfur compound sulforaphane(SFN;C6H11NOS2) is a potent cytoprotective agent promoting antioxidant, anti-inflammatory, antiglycative, and antimicrobial effects in in vitro and in vivo experimental models. Mitochondria are the major site of adenosine triphosphate(ATP) production due to the work of the oxidative phosphorylation(OXPHOS) system. They are also the main site of reactive oxygen species(ROS) production in nucleated human cells. Mitochondrial impairment is central in several human diseases, including neurodegeneration and metabolic disorders. In this paper, we describe and discuss the effects and mechanisms of action by which SFN modulates mitochondrial function and dynamics in mammalian cells. Mitochondria-related pro-apoptotic effects promoted by SFN in tumor cells are also discussed. SFN may be considered a cytoprotective agent, at least in part, because of the effects this organosulfur agent induces in mitochondria. Nonetheless, there are certain points that should be addressed in further experiments, indicated here as future directions, which may help researchers in this field of research.展开更多
Objective： Recently, a high frequency of mutations in mitochondrial DNA （mtDNA） has been detected in ovarian cancer. To explore the alterations of proteins in mitochondria in ovarian cancer, a pair of human ovarian...Objective： Recently, a high frequency of mutations in mitochondrial DNA （mtDNA） has been detected in ovarian cancer. To explore the alterations of proteins in mitochondria in ovarian cancer, a pair of human ovarian carcinoma cell lines （SKOV3/SKOV3.ip1） with different metastatic potentials was examined. Methods： Cancer cells SKOV3.ipl were derived from the ascitic tumor cells of nude mice bearing a tumor of ovarian cancer cells SKOV3. SKOV3.ipl exhibited a higher degree of migration potential than its paired cell line SKOV3. The proteins in the mi- tochondria of these two cells were isolated and separated by 2-D gel electrophoresis. The differently expressed proteins were extracted and identified using matrix assisted laser desorption ionisation/time-of-flight/time-of-flight （MALDITOF/TOF）, and finally a selected protein candidate was further investigated by immunohistochemistry （IHC） method in nude mice bearing tumor tissues of these two cells. Results： A total of 35 spots with different expressions were identified between the two cells using 2D-polyacrylamide gel electrophoresis （PAGE） approach. Among them, 17 spots were detected only in either SKOV3 or SKOV3.ipl cells. Eighteen spots expressed different levels, with as much as a three-fold difference between the two cells. Twenty spots were analyzed using MALDI-TOF/TOF, and 11 of them were identified successfully; four were known to be located in mitochondria, including superoxide dismutase 2 （SOD2）, fumarate hydratase （FH）, mitochondrial ribosomal protein L38 （MRPL38）, and mRNA turnover 4 homolog （MRTO4）. An increased staining of SOD2 was observed in SKOV3.ipl over that of SKOV3 in IHC analysis. Conclusions： Our results indicate that the enhanced antioxidation and metabolic potentials of ovarian cancer cells might contribute to their aggressive and metastatic behaviors. The underlying mechanism warrants further study.展开更多
文摘目的观察线粒体未折叠蛋白反应(mitochondrial unfolded protein response,mtUPR)在氯化锂-匹鲁卡品(pilocarpine,PILO)致痫大鼠海马神经中的变化及线粒体特异性抗氧化剂Mito-TEMPO对其影响。方法采用PILO诱导癫痫大鼠模型,并进一步采用线粒体特异性抗氧化剂Mito-TEMPO进行干预;将成年雄性Wistar大鼠随机分为空白对照组(CON组)、致痫组(PILO组)、Mito-TEMPO组和PILO+Mito-TEMPO组;采用Nissl染色观察海马神经元损伤,电子透射显微镜观察线粒体超微结构,活性氧荧光探针(DCFDA)检测线粒体ROS生成,Rhodamine123染色法检测线粒体膜电位变化,Western blot法检测线粒体热休克蛋白HSP60、蛋白酶LONP1、线粒体蛋白酶CLpP的表达。结果(1)与CON组相比,PILO组海马神经线粒体超微结构破坏严重,线粒体ROS生成增多,线粒体膜电位降低;(2)与CON组相比,PILO组海马神经HSP60、LONP1和CLpP表达增加;(3)与PILO组相比,PILO+Mito-TEMPO组线粒体超微结构破坏减轻,线粒体ROS生成明显减少,线粒体膜电位增高;(4)与PILO组相比,PILO+Mito-TEMPO组海马神经HSP60、LONP1和CLpP表达降低。结论mtUPR在癫痫海马神经损伤中明显激活,Mito-TEMPO可能通过调控mtUPR对癫痫海马线粒体损伤发挥保护作用。
文摘对12月龄SD大鼠给予L-苹果酸30d后,采用含有SYBR Green I的Real Time RT-PCR法,对肝脏和心脏线粒体苹果酸天冬氨酸穿梭中的两种转运蛋白(天冬氨酸谷氨酸转运蛋白(AGC)与α-酮戊二酸苹果酸转运蛋白(OMC))以及两种抗氧化酶(过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-Px))的基因表达进行检测,以研究L-苹果酸增强线粒体抗氧化作用的分子生物学机制。结果表明:苹果酸组中大鼠心肌细胞AGC、OMC、CAT、GSH-Px的mRNA表达量分别是空白对照组的1.25、1.39、1.12、1.01倍。苹果酸组中大鼠肝脏细胞AGC、OMC、CAT、GSH-Px的mRNA表达量分别是空白对照组的1.33、1.02、1.25、0.94倍。由此推测,L-苹果酸可能通过促进苹果酸天冬氨酸穿梭蛋白以及抗氧化酶的基因表达,实现提高线粒体的抗氧化作用。
文摘氧化应激是川崎病发病机制之一,活性氧的过量产生将导致氧化应激,控制活性氧的产生将有助于减轻氧化应激的程度,有可能改善川崎病患儿预后,因此抗氧化剂可以作为川崎病急性期的辅助疗法,特别是针对特定细胞器的靶向抗氧化剂有望成为川崎病的新型治疗措施。本文将对活性氧的产生和在川崎病中产生的病理作用,以及抗氧化剂目前的研究进展进行讨论。Oxidative stress is one of the pathogenesis of Kawasaki disease. Excessive production of reactive oxygen species will lead to oxidative stress. Controlling the production of reactive oxygen species will help to reduce the degree of oxidative stress and may improve the prognosis of children with Kawasaki disease. Therefore, antioxidants can be used as an adjuvant therapy for the acute phase of Kawasaki disease, especially for specific organelles. Targeted antioxidants are expected to become a new treatment for Kawasaki disease. This article will discuss the production of reactive oxygen species and the pathological effects in Kawasaki disease, as well as the current research progress of antioxidants.
基金Supported by Fund for Scientific Research of Shaanxi Xueqian Normal University (2013KJ033)~~
文摘[Objective] This study aimed to investigate the protective effects of aqueous extract of Eucommia ulmiodes Oliver leaves （AEO） on liver mitochondrial injury induced by free radicals. [Method] MDA content was determined by thiobarbituric acid colorimetric method; mitochondrial swelling degree was determined by spectrophotometry; the superoxide anion radical scavenging ability was determined using reduced coenzyme I-tetrazolium-phenazine methosulfate as the superoxide anion generation system. Mice were hypodermically injected in the back and neck with D- galactose, after 50 d, the effects of AEO on the activities of superoxide dismutase （SOD）, glutathione peroxidase （GSH-Px） and anti-hydroxyl radicals in mouse liver were determined using kits. [Result] AEO can efficiently reduce the liver injury and inhibit mitochondrial swelling induced by Fe2＋-L-Cys, which can also scavenge superoxide anion and improve the activities of antioxidant enzymes. [Conclusion] This study provided scientific basis for the development and application of AEO resources.
基金supported by research grants from the National Natural Science Foundation of China(No.31110103919, 31200894,31000523,30771048,30470837,31071040,and 30270638)Tianjin Municipal Sci-tech-innovation Base Project (No.10SYSYJC28400)+1 种基金Tianjin Science and Technology Planning Project(No.12JCQNJC07900)General Administration of Sport of China Basic Project(No.10B058)
文摘Mitochondrial redox metabolism has long been recognized as being central to the effects of aging and the development of age-related pathologies in the major oxidative organs. Consistent evidence has shown that exercise is able to retard the onset and impede the progression of aging by modifying mitochondrial oxidant--antioxidant homeostasis. Here we provide a broad overview of the research evidence showing the relationship between mitochondrial redox metabolism, aging and exercise. We address part aspects of mitochondrial reactive oxygen species （ROS） metabolism, from superoxide production to ROS detoxification, especially antioxidant enzymes and uncoupling protein. Furthermore, we describe mitochondrial remodeling response to aging and exercise, which is accompanied by bioenergetics and redox regulation. In addition, potential mechanisms for redox signaling involved in mitochondrial remodeling and redox metabolism regulation are also reviewed.
文摘Objective: To observe the neuroprotective mechanism of water extract of Fomito^p^is Pinicola on MPP+ induced apoptosis of mesencephala dopaminergic cells in vitro. Methods: The antioxidant activity of fungi was determined by FRAP method. The anti-inflammatory activity of the fungi was detected by LPS-induced NO release method. Mesencephalic dopaminergic neurons were labeled by TH staining to observe the survival of THir neurons. Results: In the anti-oxidant activity assay, the Trolox equivalent anti-oxidant capacity (TEAC) of water extract of Fomitopsis Pinicola was determined to be ( 165.80±7.13 )μmol Trolox/g extract. Water extracts o f Fomitopsis Pinicola treatment(100, 5 0 ,2 5 , 12.5^g/ml) decreased NO formation significantly. MPP+ induced significant chromatin condensation in the nuclei of mesencephala dopaminergic neurons with nuclear lysis, the mitochondrial membrane potential decreased remarkably, and ROS production increased significantly. Compared with the MPP+ control group, the morphological changes of cell nuclei after apoptosis was reversed by water extract of Fomitopsis Pinicola. Water extract of Fomitopsis Pinicola treatment (50,25,12.5^g/ml) dramatically increased relative mitochondrial membrane potential compared with MPP+ control respectively. Compared with the MPP+ control, water extract of Fomitopsis Pinicola treatment (50, 25^g/ml) significantly decreased relative ROS formation respectively. Conclusions: Water extract of Fomitopsis Pinicola showed significant neuroprotective effect on mesencephala dopaminergic cells induced by MPP+. The water extract of Fomitopsis Pinicola showed antioxidant and anti-inflammatory activities. The mechanism of neuroprotective effect of water extract of Fomitopsis Pinicola may be related to inhibitory on mitochondrial oxidative stress.
基金Project supported by the Jiangsu Agri-animal Husbandry Vocational College Academy Research Project(No.NSF201509)the Jiangsu University Brand Speciality Construction Work Founded Project(No.PPZY2015C230),China。
文摘Resveratrol(3,5,4’-trihydroxystilbene,RSV) has been widely used in mammalian cells,but whether it can be used during freezing boar semen is still unknown.The effects of RSV treatment during boar semen freezing on its anti-freezing ability,apoptosis,and possible apoptotic pathways were observed in this study.Sperm motility,mitochondrial membrane potential(ΔΨm),adenosine triphosphate(ATP) content,terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick-end labeling(TUNEL)-positive apoptotic state,and messenger RNA(mRNA) expression levels of apoptotic genes involved in different apoptotic pathways after freezing with or without RSV treatment were tested.The results showed that:(1) Compared with fresh sperm,the motility,normal acrosome rate,and plasma membrane integrity rate of frozen boar sperm decreased significantly(P<0.05),and RSV did not significantly increase the sperm motility(0.44 vs.0.40,P>0.05),but it did significantly improve the normal acrosome rate(57.65% vs.47.00%,P<0.05) and plasma membrane integrity rate(46.67% vs.38.85%,P<0.05).(2) After freezing,most boar sperm showed low mitochondrial ΔΨm.RSV treatment could increase the rate of high mitochondrial ΔΨm of boar sperm.(3) RSV treatment significantly decreased reactive oxygen species(ROS) levels(58.65% vs.88.41%,P<0.05)and increased the ATP content(0.49 μmol/L vs.0.25 μmol/L,P<0.05) of boar sperm during freezing.(4) The apoptotic rate of the freezing group(80.41%) with TUNEL detection increased significantly compared to the fresh group(9.70%,P<0.05),and RSV treatment greatly decreased the apoptotic rate(68.32%,P<0.05).(5) Real-time polymerase chain reaction(RT-PCR) showed that not only the genes from the death receptor-mediated apoptotic pathway(tumor necrosis factor-α(TNF-α),Fas ligand(FasL),and Caspase-8),but also the genes from the mitochondria-mediated apoptotic pathway(manganese superoxide dismutase(MnSOD),B-cell lymphoma 2(Bcl-2),Bcl-2-associated X protein(Bax),and Caspase-9) were both significantly changed after freezing.RSV treatment during freezing greatly changed their expression levels.Although RSV treatment during boar semen freezing did not significantly increase motility after thawing,it still played an efficient antioxidant role,which could enhance the mitochondrial function and decrease the apoptotic level induced by both the death receptor-and mitochondria-mediated apoptotic pathways.
基金Project supported by the National Council for Scientific and Technological Development(CNPq,No.301273/2018-9),Brazil。
文摘The organosulfur compound sulforaphane(SFN;C6H11NOS2) is a potent cytoprotective agent promoting antioxidant, anti-inflammatory, antiglycative, and antimicrobial effects in in vitro and in vivo experimental models. Mitochondria are the major site of adenosine triphosphate(ATP) production due to the work of the oxidative phosphorylation(OXPHOS) system. They are also the main site of reactive oxygen species(ROS) production in nucleated human cells. Mitochondrial impairment is central in several human diseases, including neurodegeneration and metabolic disorders. In this paper, we describe and discuss the effects and mechanisms of action by which SFN modulates mitochondrial function and dynamics in mammalian cells. Mitochondria-related pro-apoptotic effects promoted by SFN in tumor cells are also discussed. SFN may be considered a cytoprotective agent, at least in part, because of the effects this organosulfur agent induces in mitochondria. Nonetheless, there are certain points that should be addressed in further experiments, indicated here as future directions, which may help researchers in this field of research.
文摘Objective： Recently, a high frequency of mutations in mitochondrial DNA （mtDNA） has been detected in ovarian cancer. To explore the alterations of proteins in mitochondria in ovarian cancer, a pair of human ovarian carcinoma cell lines （SKOV3/SKOV3.ip1） with different metastatic potentials was examined. Methods： Cancer cells SKOV3.ipl were derived from the ascitic tumor cells of nude mice bearing a tumor of ovarian cancer cells SKOV3. SKOV3.ipl exhibited a higher degree of migration potential than its paired cell line SKOV3. The proteins in the mi- tochondria of these two cells were isolated and separated by 2-D gel electrophoresis. The differently expressed proteins were extracted and identified using matrix assisted laser desorption ionisation/time-of-flight/time-of-flight （MALDITOF/TOF）, and finally a selected protein candidate was further investigated by immunohistochemistry （IHC） method in nude mice bearing tumor tissues of these two cells. Results： A total of 35 spots with different expressions were identified between the two cells using 2D-polyacrylamide gel electrophoresis （PAGE） approach. Among them, 17 spots were detected only in either SKOV3 or SKOV3.ipl cells. Eighteen spots expressed different levels, with as much as a three-fold difference between the two cells. Twenty spots were analyzed using MALDI-TOF/TOF, and 11 of them were identified successfully; four were known to be located in mitochondria, including superoxide dismutase 2 （SOD2）, fumarate hydratase （FH）, mitochondrial ribosomal protein L38 （MRPL38）, and mRNA turnover 4 homolog （MRTO4）. An increased staining of SOD2 was observed in SKOV3.ipl over that of SKOV3 in IHC analysis. Conclusions： Our results indicate that the enhanced antioxidation and metabolic potentials of ovarian cancer cells might contribute to their aggressive and metastatic behaviors. The underlying mechanism warrants further study.
