RESUMO
Parkinson's disease (PD) is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra (SN) with the presence of alpha-synuclein inclusions termed Lewy bodies. The aggregation of alpha-synuclein into oligomeric species affects neuronal viability, having a causal role in the development of PD. The neuroprotective effects of protocatechuic acid (PAc) have been reported. However, the effects of PAc on tyrosine hydroxylase (TH) and alpha-synuclein in rat pheochromocytoma (PC12) cells treated with 1-methyl-4-phenylpyridinium ion (MPP(+)) remains unclear. In this study, we demonstrated that PAc inhibited the cytotoxicity, apoptotic morphology, reduction of TH expression and abnormal oligomeration of alpha-synuclein in PC12 cells treated with MPP(+). Taken together, our results indicate that the neuroprotective effects of PAc on PC12 cells treated with MPP(+) is related to the inhibition of the oligomerization of alpha-synuclein.
Assuntos
Dopamina/metabolismo , Hidroxibenzoatos/farmacologia , Neurotoxinas/farmacologia , Feocromocitoma/patologia , Animais , Neurotoxinas/metabolismo , Células PC12 , Ratos , Tirosina 3-Mono-Oxigenase/metabolismo , alfa-Sinucleína/metabolismoRESUMO
[This corrects the article DOI: 10.18632/oncotarget.18909.].
RESUMO
Selenium compounds have strong anti-tumor effects and are well-tolerated. We examined the anti-tumor effects of (NH4)2H15Se2VIMo10V3O52·2H2O (Se2Mo10V3), a heteropoly compound containing selenium. Se2Mo10V3 inhibited proliferation in K562 cells with a half-maximal inhibitory concentration of 78.72±2.82 mg/L after 48 h and 24.94±0.88 mg/L after 72 h. Typical apoptotic morphologies were also observed in K562 cells treated with Se2Mo10V3, as were increased intracellular levels of Ca2+, Mg2+, H+, and reactive oxygen species, and decreased mitochondrial membrane potential. In addition, Se2Mo10V3 treatment triggered cytochrome C release and inhibited IκBα degradation and NF-κB translocation. In vivo experiments revealed that 5 or 10 mg/kg Se2Mo10V3 inhibited the growth of sarcoma 180 and hepatoma 22 xenograft tumors. These results indicate that Se2Mo10V3 inhibits tumor growth both in vitro and in vivo and induces apoptosis in K562 cells, possibly by inhibiting the NF-κB/IκBα pathway.
RESUMO
Parkinson disease (PD) is the second most common neurodegenerative disease, and it cannot be completely cured by current medications. In this study, DJ-1 protein was administrated into medial forebrain bundle of PD model rats those had been microinjected with 6-hydroxydopamine (6-OHDA) or MG-132. We found that DJ-1 protein could reduce apomorphine-induced rotations, inhibit reduction of dopamine contents and tyrosine hydroxylase levels in the striatum, and decrease dopaminergic neuron death in the substantia nigra. In 6-OHDA lesioned rats, uncoupling protein-4, uncoupling protein-5 and superoxide dismutase-2 (SOD2) mRNA and SOD2 protein were increased when DJ-1 protein was co-injected. Simultaneously, administration of DJ-1 protein reduced α-synuclein and hypoxia-inducible factor 1α mRNA and α-synuclein protein in MG-132 lesioned rats. Therefore, DJ-1 protein protected dopaminergic neurons in two PD model rats by increasing antioxidant capacity and inhibiting α-synuclein expression.
Assuntos
Antiparkinsonianos/uso terapêutico , Neurônios Dopaminérgicos/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intracelular/uso terapêutico , Leupeptinas/toxicidade , Fármacos Neuroprotetores/uso terapêutico , Proteínas Oncogênicas/uso terapêutico , Oxidopamina/toxicidade , Transtornos Parkinsonianos/prevenção & controle , Animais , Antiparkinsonianos/administração & dosagem , Apomorfina/antagonistas & inibidores , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Corpo Estriado/patologia , Dopamina/análise , Neurônios Dopaminérgicos/enzimologia , Avaliação Pré-Clínica de Medicamentos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Peptídeos e Proteínas de Sinalização Intracelular/administração & dosagem , Canais Iônicos/biossíntese , Canais Iônicos/genética , Masculino , Microinjeções , Proteínas de Transporte da Membrana Mitocondrial/biossíntese , Proteínas de Transporte da Membrana Mitocondrial/genética , Proteínas Mitocondriais/biossíntese , Proteínas Mitocondriais/genética , Proteínas de Desacoplamento Mitocondrial , Atividade Motora/efeitos dos fármacos , Proteínas do Tecido Nervoso/análise , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/genética , Fármacos Neuroprotetores/administração & dosagem , Proteínas Oncogênicas/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/tratamento farmacológico , Proteína Desglicase DJ-1 , Ratos , Ratos Sprague-Dawley , Substância Negra/efeitos dos fármacos , Substância Negra/metabolismo , Substância Negra/patologia , Superóxido Dismutase/biossíntese , Superóxido Dismutase/genética , Tirosina 3-Mono-Oxigenase/análise , alfa-Sinucleína/biossíntese , alfa-Sinucleína/genéticaRESUMO
OBJECTIVE: To determine whether the expression of DJ-1 protein, whose levels in spermatozoa have been reported to be highly correlated with male infertility caused by toxicants, is changed in spermatozoa of Chinese asthenozoospermia patients. DESIGN: DJ-1 measurement by Western blotting, quantitive ELISA, and isoelectric-focusing electrophoresis (IFE) combined with immunoblotting. SETTING: Academic medical center and research laboratories. PATIENT(S): Asthenozoospermia patients (n = 113), including mild asthenozoospermia patients (n = 70) and moderate asthenozoospermia patients (n = 43), and age-matched control subjects (n = 58). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): DJ-1 in spermatozoa was determined by Western blotting and ELISA, the isoelectric point (pI) of DJ-1 by IFE combined with immunoblotting, and sperm superoxide dismutase (SOD) activity by an assay kit. RESULT(S): The sperm DJ-1 concentration in moderate asthenozoospermia patients was lower than those in mild asthenozoospermia patients and control subjects. DJ-1 with a more acidic pI was increased in asthenozoospermia patients. Sperm SOD activity was decreased in asthenozoospermia patients. CONCLUSION(S): DJ-1 levels are reduced in moderate asthenozoospermia patients. DJ-1 concentration is positively correlated with sperm motility and sperm SOD activity indicated by partial correlation analysis.
Assuntos
Povo Asiático , Astenozoospermia/metabolismo , Regulação para Baixo/fisiologia , Ejaculação/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Oncogênicas/antagonistas & inibidores , Proteínas Oncogênicas/metabolismo , Espermatozoides/metabolismo , Adulto , Povo Asiático/etnologia , Astenozoospermia/etnologia , Humanos , Masculino , Proteínas Oncogênicas/biossíntese , Proteína Desglicase DJ-1 , Motilidade dos Espermatozoides/fisiologia , Espermatozoides/enzimologia , Superóxido Dismutase/metabolismoRESUMO
Parkinson's disease (PD) is characterized by the progressive degeneration of dopaminergic neurons in substantia nigra (SN) with the presence of alpha-synuclein inclusions termed Lewy bodies. The neuroprotective effects of protocatechuic acid (PAc) both in vitro and in vivo have been reported. However, little is known about the effects of PAc on neurotoxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in vivo. In this study, we demonstrated that PAc inhibited the reduction of the latent periods in a rotarod test, and the contents of dopamine (DA) and its metabolites in striatum, and furthermore, it ameliorated the pathology in SN and the decreases in the expression of tyrosine hydroxylase (TH) in SN of C57BL/6J mice induced by MPTP. Taken together, our results indicate for the first time that PAc has neuroprotective effects on MPTP treated C57BL/6J mice and may be useful in clinical treatment of PD.