Tau, a primary component of microtubule-associated protein, promotes microtubule assembly and/or disassembly and maintains the stability of the microtubule structure. Although the importance of tau in neurodegenerativ...Tau, a primary component of microtubule-associated protein, promotes microtubule assembly and/or disassembly and maintains the stability of the microtubule structure. Although the importance of tau in neurodegenerative diseases has been well demonstrated, wheth- er tau is involved in peripheral nerve regeneration remains unknown. In the current study, we obtained sciatic nerve tissue from adult rats 0, 1, 4, 7, and 14 days after sciatic nerve crush and examined tau mRNA and protein expression levels and the location of tau in the sciatic nerve following peripheral nerve injury. The results from our quantitative reverse transcription polymerase chain reaction analysis showed that compared with the uninjured control sciatic nerve, mRNA expression levels for both tau and tau tubulin kinase 1, a serine/ threonine kinase that regulates tau phosphorylation, were decreased following peripheral nerve injury. Our western blot assay results suggested that the protein expression levels of tau and phosphorylated tau initially decreased 1 day post nerve injury but then gradually increased. The results of our immunohistochemical labeling showed that the location of tau protein was not altered by nerve injury. Thus, these results showed that the expression of tau was changed following sciatic nerve crush, suggesting that tau may be involved in periph- eral nerve repair and regeneration.展开更多
Objective: To examine the expression of the tau protein and mi-crotubule-associated proteins (MAP) in the testicular interstitium of aged and young rats. Methods: Sprague-Dawley male rats were divided into a young gro...Objective: To examine the expression of the tau protein and mi-crotubule-associated proteins (MAP) in the testicular interstitium of aged and young rats. Methods: Sprague-Dawley male rats were divided into a young group (6 months) and an aged group (28 months) of 10 animals each. The two-step immunohistochemistry method with the antibody against tau protein and MAPa was performed with the testis tissues. Results: The immunoreactive cells of the testicular interstilial tau protein were significantly increased (P<0.01) and those of the MAP significantly decreased (P<0.01) in the aged than in the young rats. Conclusion: The changes in the expression of the tau protein and MAP may be related to the aging process of the testis.展开更多
Transient brain ischemia has been shown to induce hyperphosphorylation of the micro- tubule-associated protein tau. To further determine the mechanisms underlying these processes, we investigated the interaction betwe...Transient brain ischemia has been shown to induce hyperphosphorylation of the micro- tubule-associated protein tau. To further determine the mechanisms underlying these processes, we investigated the interaction between tau, glycogen synthase kinase (GSK)-313 and protein phos- phatase 2A. The results confirmed that tau protein was dephosphorylated during brain ischemia; in addition, the activity of GSK-3β was increased and the activity of protein phosphatase 2A was de- creased. After reperfusion, tau protein was hyperphosphorylated, the activity of GSK-3β was de- creased and the activity of protein phosphatase 2A remained low. Importantly, the interaction of tau with GSK-3β and protein phosphatase 2A was altered during ischemia and reperfusion. Lithium chloride could affect tau phosphorylation by regulating the interaction of tau with GSK-3β and pro- tein phosphatase 2A, and improve learning and memory ability of rats after transient brain ischemia. The present study demonstrated that it was the interaction of tau with GSK-3β and protein phos- phatase 2A, rather than their individual activities, that dominates the phosphorylation of tau in tran- sient brain ischemia. Hyperphosphorylated tau protein may play an important role in the evolution of brain injury in ischemic stroke. The neuroprotective effects of lithium chloride partly depend on the inhibition of tau phosphorylation during transient brain ischemia.展开更多
OBJECTIVE: To quantitatively evaluate the association between tau genetic polymorphism (H1 and H2) and susceptibility to sporadic progressive supranuclear palsy (PSP). DATA SOURCES: Relevant Medical Subject Head...OBJECTIVE: To quantitatively evaluate the association between tau genetic polymorphism (H1 and H2) and susceptibility to sporadic progressive supranuclear palsy (PSP). DATA SOURCES: Relevant Medical Subject Heading terms and text words were used to identify articles from MEDLINE (1966/2010-07), EMBASE (1984/2010-07), and Chinese National Knowledge Infrastructure (1979/2010), as well as references of the retrieved articles. STUDY SELECTION: The selected articles met the following criteria: sporadic PSP case group and healthy control group, as well as genotype frequency (H1/H1 and H1/H2 + H2/H2) in cases and controls. Genotype distribution in the control groups was tested using the Hardy-Weinberg Equilibrium (HWE). Articles irrelevant to HWE were excluded, and a forest plot was performed to combine all selected articles with Review Manager (Version 5.0). MAIN OUTCOME MEASURES: The summary odds ratios arid corresponding 95% confidence intervals (95%CI) for tau polymorphism (H1/H1 and H1/H2 + H2/H2) between sporadic PSP case and healthy control groups were estimated using the fixed effects model to assess whether tau genetic polymorphism is associated with sporadic PSP susceptibility. RESULTS: According to inclusion and exclusion criteria, a total of 16 articles, which included 1 337 sporadic PSP cases and 2 073 controls, were used in the study. Two articles were excluded because of deviation from HWE in the control groups. The combined result, based on all studies, showed a significant difference in genotype distribution between cases and controls: H1H1 vs. H1H2 + H2H2 (odds ratio (OR) = 4.98, 95%C1: 3.97-6.23, P 〈 0.01). Stratifying for geographic distribution of PSP, sporadic PSP cases exhibited a significantly higher frequency of H1H1 genotypes than controls in the United States (OR = 4.07, 95%C/: 3.16-5.25, P 〈 0.01) and Europe (OR = 8.60, 95%C1: 5.05-14.64, P〈 0.01). CONCLUSION: Tau genetic polymorphism is associated with sporadic PSP susceptibility, and geographic distribution might play a role in tau genetic polymorphism and sporadic PSP susceptibility.展开更多
基金supported by the National Natural Science Foundation of China,No.81130080,31300942the National Key Basic Research Program of China(973 Program)+5 种基金No.2014CB542202the Natural Science Foundation of Jiangsu Province,China,No.BK20150409the Natural Science Foundation of Jiangsu Higher Education Institutions of China,No.15KJB180013the Scientific Research Foundation of Nantong University of China,No.14R29the Natural Science Foundation of Nantong City in China,No.MS12015043the Priority Academic Program Development of Jiangsu Higher Education Institutions of China
文摘Tau, a primary component of microtubule-associated protein, promotes microtubule assembly and/or disassembly and maintains the stability of the microtubule structure. Although the importance of tau in neurodegenerative diseases has been well demonstrated, wheth- er tau is involved in peripheral nerve regeneration remains unknown. In the current study, we obtained sciatic nerve tissue from adult rats 0, 1, 4, 7, and 14 days after sciatic nerve crush and examined tau mRNA and protein expression levels and the location of tau in the sciatic nerve following peripheral nerve injury. The results from our quantitative reverse transcription polymerase chain reaction analysis showed that compared with the uninjured control sciatic nerve, mRNA expression levels for both tau and tau tubulin kinase 1, a serine/ threonine kinase that regulates tau phosphorylation, were decreased following peripheral nerve injury. Our western blot assay results suggested that the protein expression levels of tau and phosphorylated tau initially decreased 1 day post nerve injury but then gradually increased. The results of our immunohistochemical labeling showed that the location of tau protein was not altered by nerve injury. Thus, these results showed that the expression of tau was changed following sciatic nerve crush, suggesting that tau may be involved in periph- eral nerve repair and regeneration.
文摘Objective: To examine the expression of the tau protein and mi-crotubule-associated proteins (MAP) in the testicular interstitium of aged and young rats. Methods: Sprague-Dawley male rats were divided into a young group (6 months) and an aged group (28 months) of 10 animals each. The two-step immunohistochemistry method with the antibody against tau protein and MAPa was performed with the testis tissues. Results: The immunoreactive cells of the testicular interstilial tau protein were significantly increased (P<0.01) and those of the MAP significantly decreased (P<0.01) in the aged than in the young rats. Conclusion: The changes in the expression of the tau protein and MAP may be related to the aging process of the testis.
基金supported by the National High Technology Research and Development Program of China(863 Program),No.2012AA020905the Biological Industry Development Funds of Shenzhen,No.JC201005260093A+1 种基金the National Natural Science Foundation of China/Research Grants Council Joint Research Scheme,No.81161160570the National Natural Science Foundation of China,No.81171143the Tsinghua-Yue-Yuen Medical Sciences Fund
文摘Transient brain ischemia has been shown to induce hyperphosphorylation of the micro- tubule-associated protein tau. To further determine the mechanisms underlying these processes, we investigated the interaction between tau, glycogen synthase kinase (GSK)-313 and protein phos- phatase 2A. The results confirmed that tau protein was dephosphorylated during brain ischemia; in addition, the activity of GSK-3β was increased and the activity of protein phosphatase 2A was de- creased. After reperfusion, tau protein was hyperphosphorylated, the activity of GSK-3β was de- creased and the activity of protein phosphatase 2A remained low. Importantly, the interaction of tau with GSK-3β and protein phosphatase 2A was altered during ischemia and reperfusion. Lithium chloride could affect tau phosphorylation by regulating the interaction of tau with GSK-3β and pro- tein phosphatase 2A, and improve learning and memory ability of rats after transient brain ischemia. The present study demonstrated that it was the interaction of tau with GSK-3β and protein phos- phatase 2A, rather than their individual activities, that dominates the phosphorylation of tau in tran- sient brain ischemia. Hyperphosphorylated tau protein may play an important role in the evolution of brain injury in ischemic stroke. The neuroprotective effects of lithium chloride partly depend on the inhibition of tau phosphorylation during transient brain ischemia.
文摘OBJECTIVE: To quantitatively evaluate the association between tau genetic polymorphism (H1 and H2) and susceptibility to sporadic progressive supranuclear palsy (PSP). DATA SOURCES: Relevant Medical Subject Heading terms and text words were used to identify articles from MEDLINE (1966/2010-07), EMBASE (1984/2010-07), and Chinese National Knowledge Infrastructure (1979/2010), as well as references of the retrieved articles. STUDY SELECTION: The selected articles met the following criteria: sporadic PSP case group and healthy control group, as well as genotype frequency (H1/H1 and H1/H2 + H2/H2) in cases and controls. Genotype distribution in the control groups was tested using the Hardy-Weinberg Equilibrium (HWE). Articles irrelevant to HWE were excluded, and a forest plot was performed to combine all selected articles with Review Manager (Version 5.0). MAIN OUTCOME MEASURES: The summary odds ratios arid corresponding 95% confidence intervals (95%CI) for tau polymorphism (H1/H1 and H1/H2 + H2/H2) between sporadic PSP case and healthy control groups were estimated using the fixed effects model to assess whether tau genetic polymorphism is associated with sporadic PSP susceptibility. RESULTS: According to inclusion and exclusion criteria, a total of 16 articles, which included 1 337 sporadic PSP cases and 2 073 controls, were used in the study. Two articles were excluded because of deviation from HWE in the control groups. The combined result, based on all studies, showed a significant difference in genotype distribution between cases and controls: H1H1 vs. H1H2 + H2H2 (odds ratio (OR) = 4.98, 95%C1: 3.97-6.23, P 〈 0.01). Stratifying for geographic distribution of PSP, sporadic PSP cases exhibited a significantly higher frequency of H1H1 genotypes than controls in the United States (OR = 4.07, 95%C/: 3.16-5.25, P 〈 0.01) and Europe (OR = 8.60, 95%C1: 5.05-14.64, P〈 0.01). CONCLUSION: Tau genetic polymorphism is associated with sporadic PSP susceptibility, and geographic distribution might play a role in tau genetic polymorphism and sporadic PSP susceptibility.