Objective To explore the regulatory effect of fragile X mental retardation protein （FMRP） on the translation of microtubule associated protein 1B （MAP1B）. Methods The expressions of MAP1B protein and MAP1B mRNA in...Objective To explore the regulatory effect of fragile X mental retardation protein （FMRP） on the translation of microtubule associated protein 1B （MAP1B）. Methods The expressions of MAP1B protein and MAP1B mRNA in the brains of 1-week and 6-week old fragile X mental retardation-1 （FmrI） knockout （KO） mice were investigated by immunohistochemistry, Western blot, and in situ hybridization, with the age-matched wild type mice （WT） as controls. Results The mean optical density （MOD） of MAP1B was significantly decreased in each brain region in KO6W compared with WT6W, whereas in KO1W, this decrease was only found in the hippocampus and cerebellum. MAP1B in 6-week mice was much less than that in 1-week mice of the same genotype. The results of Western blot and in situ hybridization showed that MAP1B protein and MAP1B mRNA were significantly decreased in the hippocampus of both KO1W and KO6W. Conclusion The decreased MAP1B protein and MAP1B mRNA in the Fmrl knockout mice indicate that FMRP may positively regulate the expression of MAP1B.展开更多
In this review, we discuss the role of microtubule-associated protein 1 B （MAP1B） and its phosphorylation in axonal development and regeneration in the central nervous system. MAP1B exhibits similar functions during...In this review, we discuss the role of microtubule-associated protein 1 B （MAP1B） and its phosphorylation in axonal development and regeneration in the central nervous system. MAP1B exhibits similar functions during axonal development and regeneration. MAP1B and phosphorylated MAPIB in neurons and axons maintain a dynamic balance between cytoskeletal components, and regulate the stability and interaction of microtubules and actin to promote axonal growth, neural connectivity and regeneration in the central nervous system.展开更多
BACKGROUND Colorectal cancer(CRC) is one of the main causes of cancer-related deaths in China and around the world. Advanced CRC(ACRC) patients suffer from a low cure rate though treated with targeted therapies. The r...BACKGROUND Colorectal cancer(CRC) is one of the main causes of cancer-related deaths in China and around the world. Advanced CRC(ACRC) patients suffer from a low cure rate though treated with targeted therapies. The response rate is about 50% to chemotherapy and cetuximab, a monoclonal antibody targeting epidermal growth factor receptor(EGFR) and used for ACRC with wild-type KRAS. It is important to identify more predictors of cetuximab efficacy to further improve precise treatment. Autophagy, showing a key role in the cancer progression, is influenced by the EGFR pathway. Whether autophagy can predict cetuximab efficacy in ACRC is an interesting topic.AIM To investigate the effect of autophagy on the efficacy of cetuximab in colon cancer cells and ACRC patients with wild-type KRAS.METHODS ACRC patients treated with cetuximab plus chemotherapy, with detailed data and tumor tissue, at Sun Yat-sen University Cancer Center from January 1, 2005,to October 1, 2015, were studied. Expression of autophagy-related proteins[Beclin1, microtubule-associated protein 1 A/B-light chain 3(LC3), and 4 Ebinding protein 1(4 E-BP1)] was examined by Western blot in CRC cells and by immunohistochemistry in cancerous and normal tissues. The effect of autophagy on cetuximab-treated cancer cells was confirmed by MTT assay. The associations between Beclin1, LC3, and 4 E-BP1 expression in tumor tissue and the efficacy of cetuximab-based therapy were analyzed.RESULTS In CACO-2 cells exposed to cetuximab, LC3 and 4 E-BP1 were upregulated, and P62 was downregulated. Autophagosome formation was observed, and autophagy increased the efficacy of cetuximab. In 68 ACRC patients,immunohistochemistry showed that Beclin1 levels were significantly correlated with those of LC3(0.657, P < 0.001) and 4 E-BP1(0.211, P = 0.042) in ACRC tissues.LC3 was significantly overexpressed in tumor tissues compared to normal tissues(P < 0.001). In 45 patients with wild-type KRAS, the expression levels of these three proteins were not related to progression-free survival; however, the expression levels of Beclin1(P = 0.010) and 4 E-BP1(P = 0.005), pathological grade(P = 0.002), and T stage(P = 0.004) were independent prognostic factors for overall survival(OS).CONCLUSION The effect of cetuximab on colon cancer cells might be improved by autophagy.LC3 is overexpressed in tumor tissues, and Beclin1 and 4 E-BP1 could be significant predictors of OS in ACRC patients treated with cetuximab.展开更多
Objective:To study the effect of maternal BDE-209 (brominated Diphenyl Ethers-209)exposure on the expression of microtubule-associated protein-1b (map-1b) and S-100 in rat's hippocampus of the offspring by RT-PCR....Objective:To study the effect of maternal BDE-209 (brominated Diphenyl Ethers-209)exposure on the expression of microtubule-associated protein-1b (map-1b) and S-100 in rat's hippocampus of the offspring by RT-PCR.Methods:Peanut oil suspensions of commercial deca-BDE was given in dose of 300 mg/(kg·d) by oral gavage throughout gestation and lactation in experimental group.The control group was administered only with the same capacity of peanut oil at the same time.The expression of MAP-1B in the hippocampus of the offspring's rats were tested when the pups were newborn,7days,14 days,21days and 45days old respectively by means of RT-PCR.Result:MAP-1B protein showed a statistically significantly lower concentration in the groups 14 days,21days,45days than that of the control groups.The expression of S-100 in the group which received with deca-BDE by RT-PCR showed higher than that of control groups.But only the 45days groups had significant difference of expression of MAP-1B protein compared with the control groups(P<0.05).Conclusions:Maternal BDE-209 exposure during the period of pregnancy will diminish the expression of map-1b protein in hippocampus of offspring's rats.展开更多
Previous studies have demonstrated that melatonin combined with exercise can alleviate secondary damage after spinal cord injury in rats. Therefore, it is hypothesized that melatonin combined with exercise can also al...Previous studies have demonstrated that melatonin combined with exercise can alleviate secondary damage after spinal cord injury in rats. Therefore, it is hypothesized that melatonin combined with exercise can also alleviate ischemic brain damage. In this study, adult rats were subjected to right middle cerebral artery occlusion after receiving 10 mg/kg melatonin or vehicle subcutaneously twice daily for 14 days. Forced exercise using an animal treadmill was performed at 20 m/min for 30 minutes per day for 6 days prior to middle cerebral artery occlusion. After middle cerebral artery occlusion, each rat received melatonin combined with exercise, melatonin or exercise alone equally for 7 days until sacrifice. Interestingly, rats receiving melatonin combined with exercise exhibited more severe neurological deficits than those receiving melatonin or exercise alone. Hypoxia-inducible factor la mRNA in the brain tissue was upregulated in rats receiving melatonin combined with exercise. Similarly, microtubule associated protein-2 mRNA expression was significantly upregulated in rats receiving melatonin alone. Chondroitin sulfate proteoglycan 4 （NG2） mRNA expression was significantly decreased in rats receiving melatonin combined with exercise as well as in rats receiving exercise alone. Furthermore, neural cell loss in the primary motor cortex was significantly reduced in rats receiving melatonin or exercise alone, but the change was not observed in rats receiving melatonin combined with exercise. These findings suggest that excessive intervention with melatonin, exercise or their combination may lead to negative effects on ischemia/reperfusion-induced brain damage.展开更多
Microtubule-associated protein 1B plays an important role in axon guidance and neuronal migration. In the present study, we sought to discover the mechanisms underlying microtu- bule-associated protein 1B mediation of...Microtubule-associated protein 1B plays an important role in axon guidance and neuronal migration. In the present study, we sought to discover the mechanisms underlying microtu- bule-associated protein 1B mediation of axon guidance and neuronal migration. We exposed bone marrow mesenchymal stem cells to okadaic acid or N-acetyl-D-erythro-sphingosine （an inhibitor and stimulator, respectively, of protein phosphatase 2A） for 24 hours. The expression of the phosphorylated form of type I microtubule-associated protein 1B in the cells was greater after exposure to okadaic acid and lower after N-acetyl-D-erythro-sphingosine. We then injected the bone marrow mesenchymal stem cells through the ear vein into rabbit models of spinal cord contusion. The migration of bone marrow mesenchymal stem cells towards the injured spinal cord was poorer in cells exposed to okadaic acid- and N-acetyl-D-erythro-sphingosine than in non-treated bone marrow mesenchymal stem cells. Finally, we blocked phosphatidylinosi- tol 3-kinase （PI3K） and extracellular signal-regulated kinase 1/2 （ERK1/2） pathways in rabbit bone marrow mesenchymal stem cells using the inhibitors LY294002 and U0126, respectively. LY294002 resulted in an elevated expression of phosphorylated type I microtubule-associated protein 1B, whereas U0126 caused a reduction in expression. The present data indicate that PI3K and ERKI/2 in bone marrow mesenchymal stem cells modulate the phosphorylation of micro- tubule-associated protein 1B via a cross-signaling network, and affect the migratory efficiency of bone marrow mesenchymal stem cells towards injured spinal cord.展开更多
多系统萎缩(multiple system atrophy,MSA)是一类神经系统退行性疾病,其病理特征是胶质细胞中出现含有不溶性α突触核蛋白(α-synuclein)的胞质包涵体.研究显示,α-synuclein在多系统萎缩的发病机制中有重要作用,但其毒性的分子机制目...多系统萎缩(multiple system atrophy,MSA)是一类神经系统退行性疾病,其病理特征是胶质细胞中出现含有不溶性α突触核蛋白(α-synuclein)的胞质包涵体.研究显示,α-synuclein在多系统萎缩的发病机制中有重要作用,但其毒性的分子机制目前还不清楚.本文在前期研究氧化应激条件下α-synuclein引起细胞内钙稳态失衡,提出了以氧化应激为连接的多系统萎缩中,胶质细胞死亡的新假说的基础上,深入分析了α-synuclein过表达导致U251细胞变性死亡的分子机制.首先证明过表达α-synuclein的U251细胞出现生长速度减慢、氧化应激水平增加和钙离子瞬时受体电位通道蛋白(transient receptor potential channel-1,TRPC1)表达量升高,而且细胞存活率的变化可通过下调TRPC1的表达得以恢复,说明TRPC1在α-synuclein过表达细胞死亡中发挥了重要作用;其次,研究发现α-synuclein稳转U251细胞中出现了明显的自噬水平增加和细胞凋亡的特征,表明α-synuclein通过作用于内质网钙泵以及细胞膜上的瞬时受体电位钙通道TRPC1,破坏了细胞内的钙稳态,进而影响自噬和凋亡,增加了U251细胞对于过氧化氢的敏感性,这可能是导致多系统萎缩病人脑内胶质细胞死亡的原因.展开更多
文摘Objective To explore the regulatory effect of fragile X mental retardation protein （FMRP） on the translation of microtubule associated protein 1B （MAP1B）. Methods The expressions of MAP1B protein and MAP1B mRNA in the brains of 1-week and 6-week old fragile X mental retardation-1 （FmrI） knockout （KO） mice were investigated by immunohistochemistry, Western blot, and in situ hybridization, with the age-matched wild type mice （WT） as controls. Results The mean optical density （MOD） of MAP1B was significantly decreased in each brain region in KO6W compared with WT6W, whereas in KO1W, this decrease was only found in the hippocampus and cerebellum. MAP1B in 6-week mice was much less than that in 1-week mice of the same genotype. The results of Western blot and in situ hybridization showed that MAP1B protein and MAP1B mRNA were significantly decreased in the hippocampus of both KO1W and KO6W. Conclusion The decreased MAP1B protein and MAP1B mRNA in the Fmrl knockout mice indicate that FMRP may positively regulate the expression of MAP1B.
基金supported by the National Natural Science Foundation of China(Establishment of corticospinal tract ischemic injury model in goat and axonal guidance of microtubule-associated protein 1B in bone marrow-derived mesenchymal stem cells migration in the spinal cord),No. 30972153
文摘In this review, we discuss the role of microtubule-associated protein 1 B （MAP1B） and its phosphorylation in axonal development and regeneration in the central nervous system. MAP1B exhibits similar functions during axonal development and regeneration. MAP1B and phosphorylated MAPIB in neurons and axons maintain a dynamic balance between cytoskeletal components, and regulate the stability and interaction of microtubules and actin to promote axonal growth, neural connectivity and regeneration in the central nervous system.
文摘BACKGROUND Colorectal cancer(CRC) is one of the main causes of cancer-related deaths in China and around the world. Advanced CRC(ACRC) patients suffer from a low cure rate though treated with targeted therapies. The response rate is about 50% to chemotherapy and cetuximab, a monoclonal antibody targeting epidermal growth factor receptor(EGFR) and used for ACRC with wild-type KRAS. It is important to identify more predictors of cetuximab efficacy to further improve precise treatment. Autophagy, showing a key role in the cancer progression, is influenced by the EGFR pathway. Whether autophagy can predict cetuximab efficacy in ACRC is an interesting topic.AIM To investigate the effect of autophagy on the efficacy of cetuximab in colon cancer cells and ACRC patients with wild-type KRAS.METHODS ACRC patients treated with cetuximab plus chemotherapy, with detailed data and tumor tissue, at Sun Yat-sen University Cancer Center from January 1, 2005,to October 1, 2015, were studied. Expression of autophagy-related proteins[Beclin1, microtubule-associated protein 1 A/B-light chain 3(LC3), and 4 Ebinding protein 1(4 E-BP1)] was examined by Western blot in CRC cells and by immunohistochemistry in cancerous and normal tissues. The effect of autophagy on cetuximab-treated cancer cells was confirmed by MTT assay. The associations between Beclin1, LC3, and 4 E-BP1 expression in tumor tissue and the efficacy of cetuximab-based therapy were analyzed.RESULTS In CACO-2 cells exposed to cetuximab, LC3 and 4 E-BP1 were upregulated, and P62 was downregulated. Autophagosome formation was observed, and autophagy increased the efficacy of cetuximab. In 68 ACRC patients,immunohistochemistry showed that Beclin1 levels were significantly correlated with those of LC3(0.657, P < 0.001) and 4 E-BP1(0.211, P = 0.042) in ACRC tissues.LC3 was significantly overexpressed in tumor tissues compared to normal tissues(P < 0.001). In 45 patients with wild-type KRAS, the expression levels of these three proteins were not related to progression-free survival; however, the expression levels of Beclin1(P = 0.010) and 4 E-BP1(P = 0.005), pathological grade(P = 0.002), and T stage(P = 0.004) were independent prognostic factors for overall survival(OS).CONCLUSION The effect of cetuximab on colon cancer cells might be improved by autophagy.LC3 is overexpressed in tumor tissues, and Beclin1 and 4 E-BP1 could be significant predictors of OS in ACRC patients treated with cetuximab.
文摘Objective:To study the effect of maternal BDE-209 (brominated Diphenyl Ethers-209)exposure on the expression of microtubule-associated protein-1b (map-1b) and S-100 in rat's hippocampus of the offspring by RT-PCR.Methods:Peanut oil suspensions of commercial deca-BDE was given in dose of 300 mg/(kg·d) by oral gavage throughout gestation and lactation in experimental group.The control group was administered only with the same capacity of peanut oil at the same time.The expression of MAP-1B in the hippocampus of the offspring's rats were tested when the pups were newborn,7days,14 days,21days and 45days old respectively by means of RT-PCR.Result:MAP-1B protein showed a statistically significantly lower concentration in the groups 14 days,21days,45days than that of the control groups.The expression of S-100 in the group which received with deca-BDE by RT-PCR showed higher than that of control groups.But only the 45days groups had significant difference of expression of MAP-1B protein compared with the control groups(P<0.05).Conclusions:Maternal BDE-209 exposure during the period of pregnancy will diminish the expression of map-1b protein in hippocampus of offspring's rats.
基金funded by the KRIBB Research Initiative Program,No.KGM0321112 to Y.HongBioGreen 21 Program,No.20110301-061-542-03-00 to Y.Hong,Rural Development Administration,Republic of Korea
文摘Previous studies have demonstrated that melatonin combined with exercise can alleviate secondary damage after spinal cord injury in rats. Therefore, it is hypothesized that melatonin combined with exercise can also alleviate ischemic brain damage. In this study, adult rats were subjected to right middle cerebral artery occlusion after receiving 10 mg/kg melatonin or vehicle subcutaneously twice daily for 14 days. Forced exercise using an animal treadmill was performed at 20 m/min for 30 minutes per day for 6 days prior to middle cerebral artery occlusion. After middle cerebral artery occlusion, each rat received melatonin combined with exercise, melatonin or exercise alone equally for 7 days until sacrifice. Interestingly, rats receiving melatonin combined with exercise exhibited more severe neurological deficits than those receiving melatonin or exercise alone. Hypoxia-inducible factor la mRNA in the brain tissue was upregulated in rats receiving melatonin combined with exercise. Similarly, microtubule associated protein-2 mRNA expression was significantly upregulated in rats receiving melatonin alone. Chondroitin sulfate proteoglycan 4 （NG2） mRNA expression was significantly decreased in rats receiving melatonin combined with exercise as well as in rats receiving exercise alone. Furthermore, neural cell loss in the primary motor cortex was significantly reduced in rats receiving melatonin or exercise alone, but the change was not observed in rats receiving melatonin combined with exercise. These findings suggest that excessive intervention with melatonin, exercise or their combination may lead to negative effects on ischemia/reperfusion-induced brain damage.
基金supported by the National Natural Science Foundation of China,No.81350013,81250016the Youth Science Project of National Natural Science Foundation of China,No.81301289the Youth Scientific Research Project of Jilin Provincial Science and Technology Development Plan,No.20130522032JH,20130522039JH
文摘Microtubule-associated protein 1B plays an important role in axon guidance and neuronal migration. In the present study, we sought to discover the mechanisms underlying microtu- bule-associated protein 1B mediation of axon guidance and neuronal migration. We exposed bone marrow mesenchymal stem cells to okadaic acid or N-acetyl-D-erythro-sphingosine （an inhibitor and stimulator, respectively, of protein phosphatase 2A） for 24 hours. The expression of the phosphorylated form of type I microtubule-associated protein 1B in the cells was greater after exposure to okadaic acid and lower after N-acetyl-D-erythro-sphingosine. We then injected the bone marrow mesenchymal stem cells through the ear vein into rabbit models of spinal cord contusion. The migration of bone marrow mesenchymal stem cells towards the injured spinal cord was poorer in cells exposed to okadaic acid- and N-acetyl-D-erythro-sphingosine than in non-treated bone marrow mesenchymal stem cells. Finally, we blocked phosphatidylinosi- tol 3-kinase （PI3K） and extracellular signal-regulated kinase 1/2 （ERK1/2） pathways in rabbit bone marrow mesenchymal stem cells using the inhibitors LY294002 and U0126, respectively. LY294002 resulted in an elevated expression of phosphorylated type I microtubule-associated protein 1B, whereas U0126 caused a reduction in expression. The present data indicate that PI3K and ERKI/2 in bone marrow mesenchymal stem cells modulate the phosphorylation of micro- tubule-associated protein 1B via a cross-signaling network, and affect the migratory efficiency of bone marrow mesenchymal stem cells towards injured spinal cord.
