Objective To study the relationship between apoE alleles and life-span. Methods Apolipoprotein E genotypes were determined in 164 unrelated Uygurs including 35 persons aged 90 years or older, 71 men aged 20-35 and 5...Objective To study the relationship between apoE alleles and life-span. Methods Apolipoprotein E genotypes were determined in 164 unrelated Uygurs including 35 persons aged 90 years or older, 71 men aged 20-35 and 54 men with myocardial infarction by using polymerase chain reaction-restriction fragment length polymorphism. Apolipoprotein E gene polymorphism was analyzed among three groups. Results There was statistically significant difference in the ε4 allele frequencies among three groups. The ε4 allele frequency in olds was the lowest (0.057), while in patients suffering from myocardial infarction (MI) was the highest (0.213). In MI patients the average age of first attack in ε4 allele carriers was significantly younger than that of non-carries, 51.3 and 58.3 years, respectively (P<0.05). Conclusion ApoE genotype may have some impact on human longevity.展开更多
Heterogenous nuclear ribonucleoprotein G is down-regulated in the spinal cord of the Tg(SOD1*G93A)1Gur(TG)amyotrophic lateral sclerosis mouse model.However,most studies have only examined heterogenous nuclear ribonucl...Heterogenous nuclear ribonucleoprotein G is down-regulated in the spinal cord of the Tg(SOD1*G93A)1Gur(TG)amyotrophic lateral sclerosis mouse model.However,most studies have only examined heterogenous nuclear ribonucleoprotein G expression in the amyotrophic lateral sclerosis model and heterogenous nuclear ribonucleoprotein G effects in amyotrophic lateral sclerosis pathogenesis such as in apoptosis are unknown.In this study,we studied the potential mechanism of heterogenous nuclear ribonucleoprotein G in neuronal death in the spinal cord of TG and wild-type mice and examined the mechanism by which heterogenous nuclear ribonucleoprotein G induces apoptosis.Heterogenous nuclear ribonucleoprotein G in spinal cord was analyzed using immunohistochemistry and western blotting,and cell proliferation and proteins(TAR DNA binding protein 43,superoxide dismutase 1,and Bax)were detected by the Cell Counting Kit-8 and western blot analysis in heterogenous nuclear ribonucleoprotein G siRNA-transfected PC12 cells.We analyzed heterogenous nuclear ribonucleoprotein G distribution in spinal cord in the amyotrophic lateral sclerosis model at various time points and the expressions of apoptosis and proliferation-related proteins.Heterogenous nuclear ribonucleoprotein G was mainly localized in neurons.Amyotrophic lateral sclerosis mice were examined at three stages:preonset(60-70 days),onset(90-100 days)and progression(120-130 days).The number of heterogenous nuclear ribonucleoprotein G-positive cells was significantly higher in the anterior horn of the lumbar spinal cord segment of TG mice at the preonset stage than that of control group but lower than that of the control group at the onset stage.The number of heterogenous nuclear ribonucleoprotein G-positive cells in both central canal and surrounding gray matter of the whole spinal cord of TG mice at the onset stage was significantly lower than that in the control group,whereas that of the lumbar spinal cord segment of TG mice was significantly higher than that in the control group at preonset stage and significantly lower than that in the control group at the progression stage.The numbers of heterogenous nuclear ribonucleoprotein G-positive cells in the posterior horn of cervical and thoracic segments of TG mice at preonset and progression stages were significantly lower than those in the control group.The expression of heterogenous nuclear ribonucleoprotein G in the cervical spinal cord segment of TG mice was significantly higher than that in the control group at the preonset stage but significantly lower at the progression stage.The expression of heterogenous nuclear ribonucleoprotein G in the thoracic spinal cord segment of TG mice was significantly increased at the preonset stage,significantly decreased at the onset stage,and significantly increased at the progression stage compared with the control group.heterogenous nuclear ribonucleoprotein G expression in the lumbar spinal cord segment of TG mice was significantly lower than that of the control group at the progression stage.After heterogenous nuclear ribonucleoprotein G gene silencing,PC12 cell survival was lower than that of control cells.Both TAR DNA binding protein 43 and Bax expressions were significantly increased in heterogenous nuclear ribonucleoprotein G-silenced cells compared with control cells.Our study suggests that abnormal distribution and expression of heterogenous nuclear ribonucleoprotein G might play a protective effect in amyotrophic lateral sclerosis development via preventing neuronal death by reducing abnormal TAR DNA binding protein 43 generation in the spinal cord.展开更多
The development of amyotrophic lateral sclerosis(ALS)may be related to the abnormal alterations of multiple proteins.Our previous study revealed that the expression of phosphoinositide-3-kinase regulatory subunit 4(PI...The development of amyotrophic lateral sclerosis(ALS)may be related to the abnormal alterations of multiple proteins.Our previous study revealed that the expression of phosphoinositide-3-kinase regulatory subunit 4(PIK3R4)was decreased in ALS.However,the role of PIK3R4 in ALS pathogenesis remains unknown.This study was the first to find that transfection of PC12 cells with small interfering RNA against the PIK3R4 gene significantly decreased the expression levels of PIK3R4 and the autophagy-related proteins p62 and LC3.Additionally,in vivo experiments revealed that the PIK3R4 protein was extensively expressed in the anterior horn,posterior horn,central canal,and areas surrounding the central canal in cervical,thoracic,and lumbar segments of the spinal cord in adult mice.PIK3R4 protein was mainly expressed in the neurons within the spinal lumbar segments.PIK3R4 and p62 expression levels were significantly decreased at both the pre-onset and onset stages of ALS disease in Tg(SOD1*G93A)1 Gur mice compared with control mice,but these proteins were markedly increased at the progression stage.LC3 protein expression did not change during progression of ALS.These findings suggest that PIK3R4 likely participates in the prevention of ALS progression.This study was approved by the Ethics Committee for Animal Care and Use of Jiangxi Provincial People’s Hospital,Affiliated People’s Hospital of Nanchang University(approval No.2020025)on March 26,2020.展开更多
文摘Objective To study the relationship between apoE alleles and life-span. Methods Apolipoprotein E genotypes were determined in 164 unrelated Uygurs including 35 persons aged 90 years or older, 71 men aged 20-35 and 54 men with myocardial infarction by using polymerase chain reaction-restriction fragment length polymorphism. Apolipoprotein E gene polymorphism was analyzed among three groups. Results There was statistically significant difference in the ε4 allele frequencies among three groups. The ε4 allele frequency in olds was the lowest (0.057), while in patients suffering from myocardial infarction (MI) was the highest (0.213). In MI patients the average age of first attack in ε4 allele carriers was significantly younger than that of non-carries, 51.3 and 58.3 years, respectively (P<0.05). Conclusion ApoE genotype may have some impact on human longevity.
基金supported by the National Natural Science Foundation of China,Nos.30560042,81160161,81360198,82160255Education Department of Jiangxi Province,Nos.GJJ13198 and GJJ170021+1 种基金Jiangxi Provincial Department of Science and Technology,Nos.[2014]-47,20142BBG70062,20171BAB215022,20192BAB205043Health and Family Planning Commission of Jiangxi Province,No.20181019(all to RSX).
文摘Heterogenous nuclear ribonucleoprotein G is down-regulated in the spinal cord of the Tg(SOD1*G93A)1Gur(TG)amyotrophic lateral sclerosis mouse model.However,most studies have only examined heterogenous nuclear ribonucleoprotein G expression in the amyotrophic lateral sclerosis model and heterogenous nuclear ribonucleoprotein G effects in amyotrophic lateral sclerosis pathogenesis such as in apoptosis are unknown.In this study,we studied the potential mechanism of heterogenous nuclear ribonucleoprotein G in neuronal death in the spinal cord of TG and wild-type mice and examined the mechanism by which heterogenous nuclear ribonucleoprotein G induces apoptosis.Heterogenous nuclear ribonucleoprotein G in spinal cord was analyzed using immunohistochemistry and western blotting,and cell proliferation and proteins(TAR DNA binding protein 43,superoxide dismutase 1,and Bax)were detected by the Cell Counting Kit-8 and western blot analysis in heterogenous nuclear ribonucleoprotein G siRNA-transfected PC12 cells.We analyzed heterogenous nuclear ribonucleoprotein G distribution in spinal cord in the amyotrophic lateral sclerosis model at various time points and the expressions of apoptosis and proliferation-related proteins.Heterogenous nuclear ribonucleoprotein G was mainly localized in neurons.Amyotrophic lateral sclerosis mice were examined at three stages:preonset(60-70 days),onset(90-100 days)and progression(120-130 days).The number of heterogenous nuclear ribonucleoprotein G-positive cells was significantly higher in the anterior horn of the lumbar spinal cord segment of TG mice at the preonset stage than that of control group but lower than that of the control group at the onset stage.The number of heterogenous nuclear ribonucleoprotein G-positive cells in both central canal and surrounding gray matter of the whole spinal cord of TG mice at the onset stage was significantly lower than that in the control group,whereas that of the lumbar spinal cord segment of TG mice was significantly higher than that in the control group at preonset stage and significantly lower than that in the control group at the progression stage.The numbers of heterogenous nuclear ribonucleoprotein G-positive cells in the posterior horn of cervical and thoracic segments of TG mice at preonset and progression stages were significantly lower than those in the control group.The expression of heterogenous nuclear ribonucleoprotein G in the cervical spinal cord segment of TG mice was significantly higher than that in the control group at the preonset stage but significantly lower at the progression stage.The expression of heterogenous nuclear ribonucleoprotein G in the thoracic spinal cord segment of TG mice was significantly increased at the preonset stage,significantly decreased at the onset stage,and significantly increased at the progression stage compared with the control group.heterogenous nuclear ribonucleoprotein G expression in the lumbar spinal cord segment of TG mice was significantly lower than that of the control group at the progression stage.After heterogenous nuclear ribonucleoprotein G gene silencing,PC12 cell survival was lower than that of control cells.Both TAR DNA binding protein 43 and Bax expressions were significantly increased in heterogenous nuclear ribonucleoprotein G-silenced cells compared with control cells.Our study suggests that abnormal distribution and expression of heterogenous nuclear ribonucleoprotein G might play a protective effect in amyotrophic lateral sclerosis development via preventing neuronal death by reducing abnormal TAR DNA binding protein 43 generation in the spinal cord.
基金supported by the National Natural Science Foundation of China(Nos.30560042,81160161 and 81360198)Education Department of Jiangxi Province(No.GJJ170021)+1 种基金Jiangxi Provincial Department of Science and Technology(Nos.[2014]-47,20142BBG70062,20171BAB215022,20192BAB205043)Health Commission of Jiangxi Province(No.20181019)(all to RSX)。
文摘The development of amyotrophic lateral sclerosis(ALS)may be related to the abnormal alterations of multiple proteins.Our previous study revealed that the expression of phosphoinositide-3-kinase regulatory subunit 4(PIK3R4)was decreased in ALS.However,the role of PIK3R4 in ALS pathogenesis remains unknown.This study was the first to find that transfection of PC12 cells with small interfering RNA against the PIK3R4 gene significantly decreased the expression levels of PIK3R4 and the autophagy-related proteins p62 and LC3.Additionally,in vivo experiments revealed that the PIK3R4 protein was extensively expressed in the anterior horn,posterior horn,central canal,and areas surrounding the central canal in cervical,thoracic,and lumbar segments of the spinal cord in adult mice.PIK3R4 protein was mainly expressed in the neurons within the spinal lumbar segments.PIK3R4 and p62 expression levels were significantly decreased at both the pre-onset and onset stages of ALS disease in Tg(SOD1*G93A)1 Gur mice compared with control mice,but these proteins were markedly increased at the progression stage.LC3 protein expression did not change during progression of ALS.These findings suggest that PIK3R4 likely participates in the prevention of ALS progression.This study was approved by the Ethics Committee for Animal Care and Use of Jiangxi Provincial People’s Hospital,Affiliated People’s Hospital of Nanchang University(approval No.2020025)on March 26,2020.
