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1.
J Cell Mol Med ; 23(2): 1622-1627, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30484953

RESUMO

Disabled-1 (Dab1) is best known as an adaptor protein regulating neuron migration and lamination during development. However, the exact function of Dab1 in breast cancer is unknown. In this study, we examined the expression of Dab1 in 38 breast cancer paraffin sections, as well as 60 paired frozen breast cancer and their adjacent tissues. Our results showed that Dab1 was reduced in breast cancer, and its compromised expression correlated with triple negative breast cancer phenotype, poor differentiation, as well as lymph node metastasis. Functional analysis in breast cancer cell lines demonstrated that Dab1 promoted cell apoptosis, which, at least partially, depended on its regulation of NF-κB/Bcl-2/caspase-9 pathway. Our study strongly suggests that Dab1 may be a potential tumour suppressor gene in breast cancer.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias da Mama/genética , Proteínas do Tecido Nervoso/genética , Neoplasias de Mama Triplo Negativas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose/genética , Neoplasias da Mama/patologia , Caspase 9/genética , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Células MCF-7 , Pessoa de Meia-Idade , NF-kappa B/genética , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/genética , Fator de Transcrição RelA/genética , Neoplasias de Mama Triplo Negativas/patologia , Proteína X Associada a bcl-2/genética
2.
Cereb Cortex ; 24(5): 1259-68, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-23300110

RESUMO

During embryonic development of the mammalian cerebral cortex, postmitotic cortical neurons migrate radially from the ventricular zone to the cortical plate. Proper migration involves the correct orientation of migrating neurons and the transition from a multipolar to a mature bipolar morphology. Herein, we report that the 2 isoforms of Myosin-10 (Myo10) play distinct roles in the regulation of radial migration in the mouse cortex. We show that the full-length Myo10 (fMyo10) isoform is located in deeper layers of the cortex and is involved in establishing proper migration orientation. We also demonstrate that fMyo10-dependent orientation of radial migration is mediated at least in part by the netrin-1 receptor deleted in colorectal cancer. Moreover, we show that the headless Myo10 (hMyo10) isoform is required for the transition from multipolar to bipolar morphologies in the intermediate zone. Our study reveals divergent functions for the 2 Myo10 isoforms in controlling both the direction of migration and neuronal morphogenesis during radial cortical neuronal migration.


Assuntos
Movimento Celular/genética , Córtex Cerebral/citologia , Córtex Cerebral/embriologia , Miosinas/metabolismo , Neurônios/fisiologia , Análise de Variância , Animais , Células Cultivadas , Receptor DCC , Eletroporação , Embrião de Mamíferos , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Técnicas In Vitro , Antígeno Ki-67/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas Associadas aos Microtúbulos/metabolismo , Miosinas/genética , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neurogênese , Isoformas de Proteínas/genética , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Tubulina (Proteína)/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
3.
Free Radic Biol Med ; 168: 6-15, 2021 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-33781892

RESUMO

Autism spectrum disorders (ASDs) are highly associated with oxidative stress. We have recently shown that Disconnected-interacting protein homolog 2 A (DIP2A) functions in ASD pathophysiology by regulating cortactin acetylation for spine development and synaptic transmission. However, its role is not fully understood in the context of its abundant expression in mitochondria. In this paper, we found that DIP2A was involved in superoxide dismutase (SOD)-mediated antioxidative reactions. In mice, DIP2A knockout inhibited SOD activity and increased reactive oxygen species (ROS) levels in the cerebral cortex. In vitro gain-of-function experiments further confirmed the positive role of DIP2A in scavenging ROS upon oxidative stress. Moreover, DIP2A knockout caused irregular mitochondrial morphology in the cerebral cortex and impaired mitochondrial metabolism with an over consumption of lipids for energy supply. Taken together, these results revealed unrecognized functions of DIP2A in antioxidative protection, providing another possible explanation for DIP2A-mediated ASD pathophysiology.


Assuntos
Antioxidantes , Proteína Estafilocócica A , Animais , Encéfalo/metabolismo , Camundongos , Proteínas Nucleares/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
4.
Cell Biosci ; 10: 98, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32843960

RESUMO

BACKGROUND: Schwann cells (SCs) play a crucial role in Wallerian degeneration after peripheral nerve injury. The expression of genes in SCs undergo a series of changes, which greatly affect the proliferation and apoptosis of SCs as well as the fate of peripheral nerve regeneration. However, how do these genes regulate the proliferation and apoptosis of SCs remains unclear. RESULTS: SPP1 and PKCα were found upregulated after human median peripheral nerve injury, which promoted SCs proliferation and survival. The promoted proliferation and inhibited apoptosis by SPP1 were blocked after the treatment of PKCα antagonist Gö6976. Whereas, the inhibited proliferation and enhanced apoptosis induced by silence of SPP1 could be rescued by the activation of PKCα, which suggested that SPP1 functioned through PKCα. Moreover, both CD44 and αvß3 were found expressed in SCs and increased after peripheral nerve injury. Silence of CD44 or ß3 alleviated the increased proliferation and inhibited apoptosis induced by recombinant osteopontin, suggesting the function of SPP1 on SCs were dependent on CD44 and ß3. CONCLUSION: These results suggested that SPP1 promoted proliferation and inhibited apoptosis of SCs through PKCα signaling pathway by binding with CD44 and αvß3. This study provides a potential therapeutic target for improving peripheral nerve recovery.

5.
Behav Neurol ; 2017: 2941297, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28928602

RESUMO

BACKGROUND: Long noncoding RNAs were involved in the processes of diabetes. Our study was aimed to explore clinical potential of LncRNA NONRATT021972 in diabetic neuropathic pain and investigate detailed mechanisms. METHODS: 154 patients with type 2 diabetes were enrolled as experimental group paired with control. Patients without diabetes but neuropathy were enrolled to explore exclusive role of LncRNA NONRATT021972 in neuropathy. Real-time PCR and ELISA were performed to examine expression of LncRNA and TNF-α in flood. Neuropathic pain scores were calculated with data from NPQ. Streptozotocin was used for SD adult male rats to establish diabetes for NONRATT021972 siRNA or saline treatment. Neuropathic pain behaviors and expression of TNF-α were assessed. RESULT: Patients with type 2 diabetes had a significantly higher concentration of LncRNA NONRATT021972 in blood and more severe symptoms of neuropathic pain. LncRNA NONRATT021972 was positively associated with neuropathic pain scores of type 2 diabetes. TNF-α level increased in patients with type 2 diabetes. Animal experiment showed that LncRNA NONRATT021972 siRNA attenuated inflammation via decreasing TNF-α and alleviated neuropathic pain. CONCLUSION: LncRNA NONRATT021972 increased in type 2 diabetes and was positively associated with neuropathic pain scoring in type 2 diabetes. LncRNA NONRATT021972 exacerbated neuropathic pain via TNF-α related pathways.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Neuropatias Diabéticas/diagnóstico , Neuralgia/diagnóstico , RNA Longo não Codificante/metabolismo , Idoso , Animais , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 2/genética , Neuropatias Diabéticas/genética , Neuropatias Diabéticas/metabolismo , Neuropatias Diabéticas/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuralgia/genética , Neuralgia/metabolismo , Neuralgia/terapia , Medição da Dor , RNA Longo não Codificante/genética , RNA Interferente Pequeno , Ratos , Ratos Sprague-Dawley , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/metabolismo
6.
J Mol Neurosci ; 56(4): 917-925, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25877688

RESUMO

In the present study, the effects of erythropoietin (EPO) on preventing adult neurons from apoptosis (introduced by brachial plexus avulsion) were examined, and the mechanism was analyzed. Fifty injury rat models were established in this study by using micro-hemostat forceps to pull out brachial plexus root from the intervertebral foramen in supine position. These models were divided into EPO group (avulsion + 1000 U/kg subcutaneously on alternate days) and control group (avulsion + normal saline). C5-T1 spinal cord was harvested at days 1, 2, 4, 7, and 14. Compared with the control group, the apoptosis of spinal motoneurons was significantly decreased on days 4 and 7 in the EPO group, which was also approved by TUNEL examination results. The detection of p-JNK and expression of c-Jun and cleavage of cleaved PARP (c-PARP) were also examined by immunohistochemistry and were increased immediately at day 1, and peaked at day 2, day 2, and day 4 in control group, respectively. However, the amounts were decreased and delayed by EPO treatment significantly at the same time points. In conclusion, the apoptosis of adult spinal motorneurons was associated with JNK phosphorylation, c-Jun expression, and caspase activity, and EPO-mediated neuronal protective effect is proved by downregulating the JNK phosphorylation and c-Jun expression and inhibiting of c-PARP cleavage.


Assuntos
Apoptose , Plexo Braquial/metabolismo , Eritropoetina/farmacologia , Sistema de Sinalização das MAP Quinases , Neurônios/metabolismo , Traumatismos dos Nervos Periféricos/metabolismo , Animais , Plexo Braquial/citologia , Plexo Braquial/crescimento & desenvolvimento , Plexo Braquial/lesões , Regulação para Baixo , Eritropoetina/uso terapêutico , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , MAP Quinase Quinase 4/genética , MAP Quinase Quinase 4/metabolismo , Masculino , Neurônios/efeitos dos fármacos , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Poli(ADP-Ribose) Polimerases/metabolismo , Proteólise , Ratos , Ratos Wistar
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