The membrane-anchored myelin enzyme 2′,3′-cyclic nucleotide 3′-phosphodiesterase（CNPase） was discovered in the early 1960 s and has since then troubled scientists with its peculiar catalytic activity and high exp...The membrane-anchored myelin enzyme 2′,3′-cyclic nucleotide 3′-phosphodiesterase（CNPase） was discovered in the early 1960 s and has since then troubled scientists with its peculiar catalytic activity and high expression levels in the central nervous system. Despite decades of research, the actual physiological relevance of CNPase has only recently begun to unravel. In addition to a role in myelination, CNPase is also involved in local adenosine production in traumatic brain injury and possibly has a regulatory function in mitochondrial membrane permeabilization. Although research focusing on the CNPase phosphodiesterase activity has been helpful, several open questions concerning the protein function in vivo remain unanswered. This review is focused on past research on CNPase, especially in the fields of structural biology and enzymology, and outlines the current understanding regarding the biochemical and physiological significance of CNPase, providing ideas and directions for future research.展开更多
目的研究CNPase在正常新生大鼠视网膜细胞动态发育过程中表达的变化.方法随机将15只正常新出生大鼠分为生后天数(P)1、3、5、7、14 d 5个组(P1,P3,P5,P7,P14,每组n=3),经心腔灌注固定后摘取眼球进行冰冻切片;应用免疫组织化学方法检测CN...目的研究CNPase在正常新生大鼠视网膜细胞动态发育过程中表达的变化.方法随机将15只正常新出生大鼠分为生后天数(P)1、3、5、7、14 d 5个组(P1,P3,P5,P7,P14,每组n=3),经心腔灌注固定后摘取眼球进行冰冻切片;应用免疫组织化学方法检测CNPase在新生大鼠视网膜细胞中表达的变化.结果与P3,P5,P7,P14相比,P1组视网膜CNPase阳性细胞数量增多,贯穿于视网膜外成神经细胞层.与P1相比,P3、P5和P7组CNPase阳性细胞数量减少并向神经节细胞层靠近,而且呈现递减的趋势.P14组CNPase阳性细胞消失,视网膜分层结构初步形成.结论 CNPase短暂表达于新生大鼠视网膜细胞,提示其可能帮助诱导发育中的视网膜神经节细胞分化,促进视网膜发育.展开更多
Our previous study revealed that intragastric administration of naringin improved remyelination in rats with spinal cord injury and promoted the recovery of neurological function of the injured spinal cord.This study ...Our previous study revealed that intragastric administration of naringin improved remyelination in rats with spinal cord injury and promoted the recovery of neurological function of the injured spinal cord.This study sought to reveal the mechanisms by which naringin improves oligodendrocyte precursor cell differentiation and maturation,and promotes remyelination.Spinal cord injury was induced in rats by the weight-drop method.Naringin was intragastrically administered daily（20,40 mg/kg） for 4 weeks after spinal cord injury induction.Behavioral assessment,histopathological staining,immunofluorescence spectroscopy,ultrastructural analysis and biochemical assays were employed.Naringin treatment remarkably mitigated demyelination in the white matter,increased the quality of myelinated nerve fibers and myelin sheath thickness,promoted oligodendrocyte precursor cell differentiation by upregulating the expression of NKx2.2 and 2′3′-cyclic nucleotide 3′-phosphodiesterase,and inhibited β-catenin expression and glycogen synthase kinase-3β（GSK-3β） phosphorylation.These findings indicate that naringin treatment regulates oligodendrocyte precursor cell differentiation and promotes remyelination after spinal cord injury through the β-catenin/GSK-3β signaling pathway.展开更多
BACKGROUND: There is currently considerable interest in the potential value of selective inhibitors of cyclic nucleotide phosphodiesterase 4 in the treatment of asthma. However, whether they influence eosinophilic air...BACKGROUND: There is currently considerable interest in the potential value of selective inhibitors of cyclic nucleotide phosphodiesterase 4 in the treatment of asthma. However, whether they influence eosinophilic airway inflammation-associated cough remains unclear. The objective of this study was to investigate the effects of selective phosphodiesterase 4 inhibitor SB207499 on cough response and airway inflammation in guinea pigs sensitized and challenged with ovalbumin. METHODS: Forty sensitized guinea pigs were randomly divided into four groups: control (n = 10), challenge (n = 10), SB207499 (n = 10) and aminophylline (n = 10), then challenged with aerosol of 1% ovalbumin or saline. Two hours later, animals were intraperitoneally injected with either saline, 25 mg/kg of SB207499 or aminophylline. At the 24th hour, the injection was repeated with 2.5 mg/kg and 25 mg/kg SB207499 or aminophylline, then cough response to inhaled capsaicin and airway responsiveness to methacholine inducing a 150% of the peak airway pressure to the baseline (PC150) was measured. Finally, total cell number and differentials in bronchoalveolar lavage fluid were analysed. RESULTS: The cough frequency per 3 minutes and PC150 in the challenge group were (22 +/- 4) times/3 minutes and (198 +/- 54) microg/ml, which were significantly different from (6 +/- 2) times/3 minutes and (691 +/- 81) microg/ml in the control group (P展开更多
Leber＇s congenital amaurosis（LCA）and recent gene therapy advancement for treating inherited retinopathies were extensive literature reviewed using MEDLINE,Pub Med and EMBASE. Adeno-associated viral vectors were the...Leber＇s congenital amaurosis（LCA）and recent gene therapy advancement for treating inherited retinopathies were extensive literature reviewed using MEDLINE,Pub Med and EMBASE. Adeno-associated viral vectors were the most utilised vectors for ocular gene therapy. Cone photoreceptor cells might use an alternate pathway which was not reliant of the retinal pigment epithelium（RPE）derived retinoid isomerohydrolase（RPE65）to access the 11-cis retinal dehydechromophore. Research efforts dedicated on the progression of a gene-based therapy for the treatment of LCA2. Such gene therapy approaches were extremely successful in canine,porcine and rodent LCA2 models. The recombinant AAV2.h RPE65v2 adenoassociated vector contained the RPE65 cDNA and was replication deficient. Its in vitro injection in target cells induced RPE65 protein production. The gene therapy trials that were so far conducted for inherited retinopathies have generated promising results. Phase I clinical trials to cure LCA and choroideremia demonstrated that adeno-associated viral vectors containing RPE genes and photoreceptors respectively,could be successfully administered to inherited retinopathy patients. A phase III trial is presently ongoing and if successful,it will lead the way to additional gene therapy attempts to cure monogenic,inherited retinopathies.展开更多
基金supported by grants from the Department of Biochemistry,University of Ouluthe Sigrid Jusélius Foundation (Finland)+1 种基金the Academy of Finlandthe Hamburg Research and Science Foundation (Germany)
文摘The membrane-anchored myelin enzyme 2′,3′-cyclic nucleotide 3′-phosphodiesterase（CNPase） was discovered in the early 1960 s and has since then troubled scientists with its peculiar catalytic activity and high expression levels in the central nervous system. Despite decades of research, the actual physiological relevance of CNPase has only recently begun to unravel. In addition to a role in myelination, CNPase is also involved in local adenosine production in traumatic brain injury and possibly has a regulatory function in mitochondrial membrane permeabilization. Although research focusing on the CNPase phosphodiesterase activity has been helpful, several open questions concerning the protein function in vivo remain unanswered. This review is focused on past research on CNPase, especially in the fields of structural biology and enzymology, and outlines the current understanding regarding the biochemical and physiological significance of CNPase, providing ideas and directions for future research.
文摘目的研究CNPase在正常新生大鼠视网膜细胞动态发育过程中表达的变化.方法随机将15只正常新出生大鼠分为生后天数(P)1、3、5、7、14 d 5个组(P1,P3,P5,P7,P14,每组n=3),经心腔灌注固定后摘取眼球进行冰冻切片;应用免疫组织化学方法检测CNPase在新生大鼠视网膜细胞中表达的变化.结果与P3,P5,P7,P14相比,P1组视网膜CNPase阳性细胞数量增多,贯穿于视网膜外成神经细胞层.与P1相比,P3、P5和P7组CNPase阳性细胞数量减少并向神经节细胞层靠近,而且呈现递减的趋势.P14组CNPase阳性细胞消失,视网膜分层结构初步形成.结论 CNPase短暂表达于新生大鼠视网膜细胞,提示其可能帮助诱导发育中的视网膜神经节细胞分化,促进视网膜发育.
基金supported by the Natural Science Foundation of Beijing of China,No.7164317the Beijing Tsinghua Changgung Hospital Fund,No.12015C1028the National Natural Science Foundation of China,No.31400717
文摘Our previous study revealed that intragastric administration of naringin improved remyelination in rats with spinal cord injury and promoted the recovery of neurological function of the injured spinal cord.This study sought to reveal the mechanisms by which naringin improves oligodendrocyte precursor cell differentiation and maturation,and promotes remyelination.Spinal cord injury was induced in rats by the weight-drop method.Naringin was intragastrically administered daily（20,40 mg/kg） for 4 weeks after spinal cord injury induction.Behavioral assessment,histopathological staining,immunofluorescence spectroscopy,ultrastructural analysis and biochemical assays were employed.Naringin treatment remarkably mitigated demyelination in the white matter,increased the quality of myelinated nerve fibers and myelin sheath thickness,promoted oligodendrocyte precursor cell differentiation by upregulating the expression of NKx2.2 and 2′3′-cyclic nucleotide 3′-phosphodiesterase,and inhibited β-catenin expression and glycogen synthase kinase-3β（GSK-3β） phosphorylation.These findings indicate that naringin treatment regulates oligodendrocyte precursor cell differentiation and promotes remyelination after spinal cord injury through the β-catenin/GSK-3β signaling pathway.
文摘BACKGROUND: There is currently considerable interest in the potential value of selective inhibitors of cyclic nucleotide phosphodiesterase 4 in the treatment of asthma. However, whether they influence eosinophilic airway inflammation-associated cough remains unclear. The objective of this study was to investigate the effects of selective phosphodiesterase 4 inhibitor SB207499 on cough response and airway inflammation in guinea pigs sensitized and challenged with ovalbumin. METHODS: Forty sensitized guinea pigs were randomly divided into four groups: control (n = 10), challenge (n = 10), SB207499 (n = 10) and aminophylline (n = 10), then challenged with aerosol of 1% ovalbumin or saline. Two hours later, animals were intraperitoneally injected with either saline, 25 mg/kg of SB207499 or aminophylline. At the 24th hour, the injection was repeated with 2.5 mg/kg and 25 mg/kg SB207499 or aminophylline, then cough response to inhaled capsaicin and airway responsiveness to methacholine inducing a 150% of the peak airway pressure to the baseline (PC150) was measured. Finally, total cell number and differentials in bronchoalveolar lavage fluid were analysed. RESULTS: The cough frequency per 3 minutes and PC150 in the challenge group were (22 +/- 4) times/3 minutes and (198 +/- 54) microg/ml, which were significantly different from (6 +/- 2) times/3 minutes and (691 +/- 81) microg/ml in the control group (P
文摘Leber＇s congenital amaurosis（LCA）and recent gene therapy advancement for treating inherited retinopathies were extensive literature reviewed using MEDLINE,Pub Med and EMBASE. Adeno-associated viral vectors were the most utilised vectors for ocular gene therapy. Cone photoreceptor cells might use an alternate pathway which was not reliant of the retinal pigment epithelium（RPE）derived retinoid isomerohydrolase（RPE65）to access the 11-cis retinal dehydechromophore. Research efforts dedicated on the progression of a gene-based therapy for the treatment of LCA2. Such gene therapy approaches were extremely successful in canine,porcine and rodent LCA2 models. The recombinant AAV2.h RPE65v2 adenoassociated vector contained the RPE65 cDNA and was replication deficient. Its in vitro injection in target cells induced RPE65 protein production. The gene therapy trials that were so far conducted for inherited retinopathies have generated promising results. Phase I clinical trials to cure LCA and choroideremia demonstrated that adeno-associated viral vectors containing RPE genes and photoreceptors respectively,could be successfully administered to inherited retinopathy patients. A phase III trial is presently ongoing and if successful,it will lead the way to additional gene therapy attempts to cure monogenic,inherited retinopathies.
