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1.
Environ Health Prev Med ; 24(1): 36, 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31101002

RESUMO

BACKGROUND: Melanin is detectable in various sense organs including the skin in animals. It has been reported that melanin adsorbs toxic elements such as mercury, cadmium, and lead. In this study, we investigated the adsorption of molybdenum, which is widely recognized as a toxic element, by melanin. METHODS: Molybdenum level of the mouse skin was measured by inductively coupled plasma mass spectrometry. The pigmentation level of murine skin was digitalized as the L* value by using a reflectance spectrophotometer. An in vitro adsorption assay was performed to confirm the interaction between molybdenum and melanin. RESULTS: Our analysis of hairless mice with different levels of skin pigmentation showed that the level of molybdenum increased with an increase in the level of skin pigmentation (L* value). Moreover, our analysis by Spearman's correlation coefficient test showed a strong correlation (r = - 0.9441, p < 0.0001) between L* value and molybdenum level. Our cell-free experiment using the Langmuir isotherm provided evidence for the adsorption of molybdenum by melanin. The maximum adsorption capacity of 1 mg of synthetic melanin for molybdenum was 131 µg in theory. CONCLUSION: Our in vivo and in vitro results showed a new aspect of melanin as an adsorbent of molybdenum.


Assuntos
Melaninas/química , Molibdênio/química , Poluentes Químicos da Água/química , Adsorção , Animais , Melaninas/metabolismo , Camundongos , Camundongos Pelados , Camundongos Transgênicos , Molibdênio/metabolismo , Molibdênio/farmacologia , Pele/química , Pele/efeitos dos fármacos , Pigmentação da Pele/efeitos dos fármacos , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/farmacologia
2.
Sci Rep ; 8(1): 13199, 2018 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-30181591

RESUMO

Psychological stress can cause dysfunction of the gastrointestinal tract by regulating its interaction with central nervous system (brain-gut axis). Chronic social defeat stress (CSDS) is widely used to produce a rodent model of stress-induced human mood disorders and depression. We previously showed that CSDS significantly affects the intestinal ecosystem including cecal and fecal microbiota, intestinal gene expression profiles and cecal metabolite profiles. Here, we investigated whether the glycosylation pattern in the intestinal epithelium was affected in C57BL/6 mice exposed to CSDS (hereinafter referred to as CSDS mice). A lectin microarray analysis revealed that CSDS significantly reduced the reactivity of fucose-specific lectins (rAOL, TJA-II, rAAL, rGC2, AOL, AAL, rPAIIL and rRSIIL) with distal intestinal mucosa, but not with mucosa from proximal intestine and colon. Flow cytometric analysis confirmed the reduced TJA-II reactivity with intestinal epithelial cells in CSDS mice. In addition, distal intestine expression levels of the genes encoding fucosyltransferase 1 and 2 (Fut1 and Fut2) were downregulated in CSDS mice. These findings suggest that CSDS alters the fucosylation pattern in the distal intestinal epithelium, which could be used as a sensitive marker for CSDS exposure.

3.
Chemosphere ; 210: 384-391, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30015129

RESUMO

At present, beneficial effects of melanin and harmful effects of barium have been reported. However, little is known about the adsorption of barium, and even less is known about the biological significance of adsorption of barium by melanin. In this study, we showed that there was a strong correlation between the digitalized level of skin pigmentation and barium level in murine skin compared to the correlations between skin pigmentation level and levels of homologous elements of barium (magnesium, calcium and strontium). The concentration of subcutaneously injected barium in skin with a high level of pigmentation was higher than that in skin with a low level of pigmentation. Our cell-free experiment using the Langmuir isotherm for adsorption of barium in synthetic melanin also provided direct evidence of adsorption of barium by melanin. We then investigated the biological significance of melanin-mediated barium adsorption. We found barium-mediated increase in transforming activity in pigmented melanocytes (melan-a) but not in unpigmented melanocytes (melan-c) after confirming that the barium level in melan-a melanocytes was 3.4-fold higher than that in melan-c melanocytes after culture of 5 µM barium for 24 h. Taken together, our results not only indicate adsorption of barium by melanin in mice, cells and cell-free systems but also suggest a disadvantageous effect of adsorption of barium by melanin on transforming activity in cultured cells.


Assuntos
Bário/metabolismo , Melaninas/metabolismo , Pigmentação/efeitos dos fármacos , Adsorção , Animais , Bário/farmacologia , Sistema Livre de Células , Células Cultivadas , Humanos , Melanócitos/metabolismo , Camundongos
4.
Hum Mol Genet ; 26(23): 4642-4656, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-28973191

RESUMO

Alzheimer's disease (AD) is the most common neurodegenerative disorder among the elderly. During the progression of AD, massive neuronal degeneration occurs in the late stage of the disease; however, the molecular mechanisms responsible for this neuronal loss remain unknown. AßpE3-42 (an N-terminal-truncated amyloid-ß peptide that begins with pyroglutamate at the third position) is produced during late-stage AD. It also aggregates more rapidly in vitro and exhibits greater toxicity in neurons than full-length Aß1-42. In the present study, we established a Drosophila melanogaster model that expresses Aß3-42E3Q, which effectively produces AßpE3-42, and investigated the function of AßpE3-42 using the photoreceptor neurons of Drosophila. AßpE3-42 induced caspase-dependent apoptosis and caused progressive degeneration in photoreceptor neurons. Mutations in ER stress response genes or the administration of an inhibitor of the ER stress response markedly suppressed the degeneration phenotype, suggesting that the ER stress response plays an important role in neurodegeneration caused by AßpE3-42. We also confirmed that human Tau-dependent apoptotic induction was strongly enhanced by AßpE3-42. Thus, AßpE3-42 expression system in the fly may be a promising new tool for studying late-onset neurodegeneration in AD.


Assuntos
Peptídeos beta-Amiloides/biossíntese , Estresse do Retículo Endoplasmático/fisiologia , Doenças Neurodegenerativas/metabolismo , Fragmentos de Peptídeos/biossíntese , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/metabolismo , Animais , Apoptose/fisiologia , Encéfalo/metabolismo , Caspases/metabolismo , Modelos Animais de Doenças , Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/patologia , Neurônios/metabolismo , Neurônios/patologia , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo , Ácido Pirrolidonocarboxílico/metabolismo
5.
Sci Rep ; 7(1): 6844, 2017 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-28754998

RESUMO

There is no information on the association between oral exposure to arsenic (As) and hearing loss in humans or mice. In this combined epidemiological study and experimental study, the association of oral exposure to As with hearing loss in people aged 12-29 years and young mice was examined. Subjects in the exposure group (n = 48), who were drinking tube well water contaminated with As, showed significantly higher risks of hearing loss at 4 kHz [odds ratio (OR) = 7.60; 95% confidence interval (CI): 1.56, 57.88], 8 kHz (OR = 5.00; 95% CI: 1.48, 18.90) and 12 kHz (OR = 8.72; 95% CI: 2.09, 47.77) than did subjects in the control group (n = 29). We next performed an experiment in which young mice were exposed to As via drinking water at 22.5 mg/L, which is a much greater concentration than that in human studies. The exposure group showed hearing loss and accumulation of As in inner ears. Ex vivo exposure of the organ of Corti from mice exposed to As significantly decreased the number of auditory neurons and fibers. Thus, our combined study showed that oral exposure to As caused hearing loss in young people and young mice.

6.
Aging (Albany NY) ; 8(3): 427-39, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26959388

RESUMO

Increasing evidence indicates that defects in the sensory system are highly correlated with age-related neurodegenerative diseases, including Alzheimer's disease (AD). This raises the possibility that sensory cells possess some commonalities with neurons and may provide a tool for studying AD. The sensory system, especially the auditory system, has the advantage that depression in function over time can easily be measured with electrophysiological methods. To establish a new mouse AD model that takes advantage of this benefit, we produced transgenic mice expressing amyloid-ß (Aß), a causative element for AD, in their auditory hair cells. Electrophysiological assessment indicated that these mice had hearing impairment, specifically in high-frequency sound perception (>32 kHz), at 4 months after birth. Furthermore, loss of hair cells in the basal region of the cochlea, which is known to be associated with age-related hearing loss, appeared to be involved in this hearing defect. Interestingly, overexpression of human microtubule-associated protein tau, another factor in AD development, synergistically enhanced the Aß-induced hearing defects. These results suggest that our new system reflects some, if not all, aspects of AD progression and, therefore, could complement the traditional AD mouse model to monitor Aß-induced neuronal dysfunction quantitatively over time.


Assuntos
Doença de Alzheimer/complicações , Peptídeos beta-Amiloides/metabolismo , Modelos Animais de Doenças , Células Ciliadas Auditivas/metabolismo , Perda Auditiva de Alta Frequência/etiologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Feminino , Células Ciliadas Auditivas/patologia , Perda Auditiva de Alta Frequência/metabolismo , Perda Auditiva de Alta Frequência/patologia , Masculino , Camundongos Transgênicos , Proteínas tau/metabolismo
7.
Int J Clin Exp Pathol ; 8(8): 9326-31, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26464684

RESUMO

Since effective therapies for melanoma with BRAF(V600E) mutation are being developed, interest has been shown in the development of therapies for melanoma without BRAF(V600E) mutation. Recently, interest has also been shown in medical application of non-nequilibrium atmospheric pressure plasmas (NEAPPs). We previously suggested that repeated NEAPP irradiation to spontaneously developed benign melanocytic tumors in RFP-RET-transgenic mice (RET-mice) not only suppresses tumor growth but also prevents malignant transformation. In this study, we first confirmed that transcript expression levels of tumor growth regulators (CyclinD1, D2, E1, E2, G2 and PCNA but not CyclinG1) and tumor invasion regulators [Matrix metalloproteinase (MMP)-2, -9 and -14 and melanoma cell adhesion molecule (MCAM)] in melanomas were significantly higher than those in benign melanocytic tumors in RET-mice. We then showed that transcript expression levels of CyclinE1, G1 and G2 and MMP-2 and -9 in melanomas from RET-mice were significantly decreased by single NEAPP irradiation, whereas transcript expression levels of CyclinD1, D2, E2, PCNA, MCAM and MMP-14 were comparable in untreated and NEAPP-treated melanomas. Since no Braf(V600E) mutation melanomas have been found in RET-mice, our results suggest that single NEAPP irradiation is a potential therapeutic tool for melanoma without BRAF(V600E) mutation through modulation of the expression levels of tumor growth and invasion regulators.


Assuntos
Antígeno CD146/metabolismo , Transformação Celular Neoplásica/efeitos da radiação , Ciclinas/metabolismo , Metaloproteinases da Matriz/metabolismo , Melanoma/radioterapia , Neoplasias Cutâneas/radioterapia , Animais , Antígeno CD146/genética , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Ciclinas/genética , Metaloproteinases da Matriz/genética , Melanoma/genética , Melanoma/metabolismo , Camundongos , Camundongos Transgênicos , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo
8.
Nihon Eiseigaku Zasshi ; 70(3): 176-80, 2015.
Artigo em Japonês | MEDLINE | ID: mdl-26411934

RESUMO

Environmental factors affecting human health are generally classified into physical, chemical and biological factors. In this review article, we focus on ultraviolet (UV) as a physical factor, heavy metals as a chemical factor and Japanese cedar pollens as a biological factor. Since we believe that progress based on both fieldwork research and experimental research is essential in hygiene study, we included the results of both the research approached. We first introduced the mechanism of development of and prevention of UV-mediated skin melanoma in our experimental research after showing our epidemiological research on UV-mediated DNA damage in humans. We then introduced our evaluation of toxicity and development of a remediation system in our experimental research on heavy metals after showing our fieldwork research for the monitoring of drinking water from wells in Asian countries. We finally introduced the results of pathogenic analysis of pollinosis in our clinical study. We would be very happy if young researchers would re-realize the importance of experimental research as well as epidemiological research in hygiene study.


Assuntos
Exposição Ambiental , Poluentes Ambientais , Poluição Química da Água/prevenção & controle , Animais , Cryptomeria , Dano ao DNA , Água Potável , Exposição Ambiental/efeitos adversos , Monitoramento Ambiental , Poluentes Ambientais/efeitos adversos , Humanos , Melanoma/etiologia , Melanoma/prevenção & controle , Metais Pesados/efeitos adversos , Camundongos , Pólen/efeitos adversos , Rinite Alérgica Sazonal , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/prevenção & controle , Raios Ultravioleta/efeitos adversos , Poluentes Químicos da Água/efeitos adversos
9.
Sci Rep ; 5: 10821, 2015 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-26027742

RESUMO

Methylene blue (MB) inhibits the aggregation of tau, a main constituent of neurofibrillary tangles. However, MB's mode of action in vivo is not fully understood. MB treatment reduced the amount of sarkosyl-insoluble tau in Drosophila that express human wild-type tau. MB concurrently ameliorated the climbing deficits of transgenic tau flies to a limited extent and diminished the climbing activity of wild-type flies. MB also decreased the survival rate of wild-type flies. Based on its photosensitive efficacies, we surmised that singlet oxygen generated through MB under light might contribute to both the beneficial and toxic effects of MB in vivo. We identified rose bengal (RB) that suppressed tau accumulation and ameliorated the behavioral deficits to a lesser extent than MB. Unlike MB, RB did not reduce the survival rate of flies. Our findings indicate that singlet oxygen generators with little toxicity may be suitable drug candidates for treating tauopathies.


Assuntos
Oxigênio Singlete/metabolismo , Tauopatias/metabolismo , Proteínas tau/metabolismo , Animais , Animais Geneticamente Modificados , Autofagia , Comportamento Animal , Modelos Animais de Doenças , Drosophila , Feminino , Humanos , Masculino , Azul de Metileno/farmacologia , Estresse Oxidativo , Solubilidade , Tauopatias/tratamento farmacológico , Proteínas tau/química
10.
Nihon Eiseigaku Zasshi ; 70(2): 100-4, 2015.
Artigo em Japonês | MEDLINE | ID: mdl-25994339

RESUMO

Noise stress generated in industry is one of the environmental factors that physically affects the functions of the inner ear. Exposure to noise can cause hearing loss, resulting in serious problems in occupational and daily life. At present, however, there are very limited ways to prevent hearing impairments. The inner ear consists of the organ of Corti, vestibule and semicircular canal. Functional or morphological damage of these tissues in the inner ear caused by genetic factors, aging or environmental factors can result in hearing or balance impairments. In this review, we first introduce a deafness-related molecule found by our clinical research. Our experimental research using genetically engineered mice further demonstrated that impaired activity of the target molecule caused congenital and age-related hearing loss with neurodegeneration of spiral ganglion neurons in the inner ears. We also describe impaired balance in mice caused by exposure to low-frequency noise under experimental conditions with indoor environmental monitoring. We believe that our approaches to pursue both experimental research and fieldwork research complementarily are crucial for the development of a method for prevention of impairments of the inner ear.


Assuntos
Orelha Interna , Exposição Ambiental/efeitos adversos , Perda Auditiva/etiologia , Ruído/efeitos adversos , Exposição Ocupacional/efeitos adversos , Envelhecimento/patologia , Envelhecimento/fisiologia , Animais , Animais Geneticamente Modificados , Orelha Interna/anatomia & histologia , Orelha Interna/inervação , Orelha Interna/patologia , Perda Auditiva/prevenção & controle , Humanos , Camundongos , Degeneração Neural , Neurônios/patologia , Ruído Ocupacional/efeitos adversos , Gânglio Espiral da Cóclea/patologia
11.
Nihon Eiseigaku Zasshi ; 70(2): 105-9, 2015.
Artigo em Japonês | MEDLINE | ID: mdl-25994340

RESUMO

Heavy-metal pollution occurs in various environments, including water, air and soil, and has serious effects on human health. Since heavy-metal pollution in drinking water causes various diseases including skin cancer, it has become a global problem worldwide. However, there is limited information on the mechanism of development of heavy-metal-mediated disease. We performed both fieldwork and experimental studies to elucidate the levels of heavy-metal pollution and mechanisms of development of heavy-metal-related disease and to develop a novel remediation system. Our fieldwork in Bangladesh, Vietnam and Malaysia demonstrated that drinking well water in these countries was polluted with high concentrations of several heavy metals including arsenic, barium, iron and manganese. Our experimental studies based on the data from our fieldwork demonstrated that these heavy metals caused skin cancer and hearing loss. Further experimental studies resulted in the development of a novel remediation system with which toxic heavy metals were absorbed from polluted drinking water. Implementation of both fieldwork and experimental studies is important for prediction, prevention and therapy of heavy-metal-mediated diseases.


Assuntos
Água Potável/química , Metais Pesados/efeitos adversos , Metais Pesados/análise , Poluentes Químicos da Água/efeitos adversos , Poluentes Químicos da Água/análise , Poluição Química da Água/efeitos adversos , Poluição Química da Água/análise , Bangladesh , Perda Auditiva/induzido quimicamente , Perda Auditiva/prevenção & controle , Humanos , Malásia , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/prevenção & controle , Vietnã , Purificação da Água/métodos
12.
J Invest Dermatol ; 135(4): 1147-1156, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25493652

RESUMO

Various cancers including skin cancer are increasing in 45 million people exposed to arsenic above the World Health Organization's guideline value of 10 µg l(-1). However, there is limited information on key molecules regulating arsenic-mediated carcinogenesis. Our fieldwork in Bangladesh demonstrated that levels of placental growth factor (PlGF) in urine samples from residents of cancer-prone areas with arsenic-polluted drinking water were higher than those in urine samples from residents of an area that was not polluted with arsenic. Our experimental study in human nontumorigenic HaCaT skin keratinocytes showed that arsenite promoted anchorage-independent growth with increased expression and secretion of PlGF, a ligand of vascular endothelial growth factor receptor1 (VEGFR1), and increased VEGFR1/mitogen-activated protein kinase/ERK kinase (MEK)/extracellular signal-regulated kinase (ERK) activities. The arsenite-mediated promotion of anchorage-independent growth was strongly inhibited by PlGF depletion with decreased activities of the PlGF/VEGFR1/MEK/ERK pathway. Moreover, arsenite proteasome-dependently degrades metal-regulatory transcription factor-1 (MTF-1) protein, resulting in a decreased amount of MTF-1 protein binding to the PlGF promoter. MTF-1 negatively controlled PlGF transcription in HaCaT cells, resulting in increased PlGF transcription. These results suggest that arsenite-mediated MTF-1 degradation enhances the activity of PlGF/VEGFR1/MEK/ERK signaling, resulting in promotion of the malignant transformation of keratinocytes. Thus, this study proposed a molecular mechanism for arsenite-mediated development of skin cancer.


Assuntos
Intoxicação por Arsênico/metabolismo , Arsênico/toxicidade , Arsenitos/química , Proteínas da Gravidez/fisiologia , Neoplasias Cutâneas/induzido quimicamente , Animais , Arsênico/química , Arsenitos/urina , Bangladesh , Adesão Celular , Linhagem Celular , Linhagem Celular Tumoral , Transformação Celular Neoplásica , Modelos Animais de Doenças , Poluentes Ambientais , Humanos , Imuno-Histoquímica , Queratinócitos/efeitos dos fármacos , MAP Quinase Quinase Quinases/metabolismo , Camundongos , Fator de Crescimento Placentário , Proteínas da Gravidez/metabolismo , Proteínas da Gravidez/urina , Complexo de Endopeptidases do Proteassoma/química , Interferência de RNA , RNA Mensageiro/metabolismo , Transdução de Sinais , Urina/química , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Poluentes Químicos da Água/urina
14.
Environ Health Prev Med ; 19(5): 367-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25037598

RESUMO

Due to the increased ultraviolet radiation, the incidence of melanoma is increasing worldwide more than that of any other cancer. In this study, the effects of irradiation of non-thermal atmospheric pressure plasmas (NEAPPs) on benign melanocytic tumors from our original hairless model mice (HL-RET-mice), in which benign melanocytic tumors and melanomas spontaneously develop in the skin stepwise, were examined. Expression levels of melanoma cell adhesion molecule (MCAM) and matrix metalloproteinase-2 (MMP-2) mRNA in melanomas were higher than those in benign melanocytic tumors in the mice. Repeated irradiation of non-thermal atmospheric pressure plasmas (NEAPPs) for the benign tumors decreased the expression levels of MCAM and MMP-2 mRNA in the tumors from the mice. Previous studies showed that MCAM sites are upstream of MMP-2, that MCAM regulates transcription of MMP-2 in melanoma cells and that MMP-2 is associated with the conversion of a benign tumor to a malignant tumor. Therefore, our results suggest that the NEAPP irradiation-mediated decrease in the expression level of MMP-2 in benign melanocytic tumors is associated with decreased expression levels of MCAM. Moreover, NEAPP irradiation might be a potential candidate for therapy to prevent melanoma development through suppression of malignant conversion in benign melanocytic tumors.


Assuntos
Regulação Neoplásica da Expressão Gênica , Melanoma/genética , Melanoma/radioterapia , Gases em Plasma/uso terapêutico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/radioterapia , Animais , Pressão Atmosférica , Antígeno CD146/genética , Antígeno CD146/metabolismo , Transformação Celular Neoplásica/efeitos da radiação , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Camundongos , Camundongos Pelados , Reação em Cadeia da Polimerase , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
15.
Exp Dermatol ; 23(6): 424-5, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24750453

RESUMO

The incidence of cutaneous malignant melanoma is increasing at a greater rate than that of any other cancer in the world. However, an effective therapy for malignant melanoma has not been established. Recently, some studies have shown an antitumor effect of non-equilibrium atmospheric pressure plasmas (NEAPPs) in vitro. Here, we examined the in vivo effect of NEAPP on cell cycle regulators, key elements for malignant transformation, in spontaneously developed benign melanocytic tumors in a hairless animal model. NEAPP irradiation decreased expression levels of cell cycle promoters, Cyclin D1, E1 and E2, and increased expression level of a cell cycle repressor, p27(KIP) (1) . Cyclin D1, E1 and E2 and p27(KIP) expression levels were associated with malignant transformation of the benign tumor in the animal model. Our results suggest that NEAPP irradiation suppresses malignant transformation of a benign melanocytic tumor via control of the expression levels of cell cycle regulators.


Assuntos
Argônio/uso terapêutico , Proteínas de Ciclo Celular/genética , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Nevo Pigmentado/genética , Proteínas Proto-Oncogênicas c-ret/genética , Radioterapia/métodos , Neoplasias Cutâneas/genética , Animais , Pressão Atmosférica , Ciclo Celular/genética , Ciclo Celular/efeitos da radiação , Proteínas de Ciclo Celular/efeitos da radiação , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/efeitos da radiação , Modelos Animais de Doenças , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/genética , Camundongos , Camundongos Pelados , Camundongos Transgênicos , Nevo Pigmentado/patologia , Nevo Pigmentado/radioterapia , Neoplasias Cutâneas/prevenção & controle , Neoplasias Cutâneas/radioterapia
16.
Arch Toxicol ; 88(5): 1185-6, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24614979

RESUMO

Krishna et al. (Arch Toxicol 88(1):47-64, 2014) recently published the results of a study in which adult C57BL/6 mice were subchronically exposed to 400,000 µg/L manganese (Mn) using manganese chloride via drinking water for 8 weeks and examined the neurotoxic effects. After 5 weeks of Mn exposure, significant deposition of Mn in all of the brain regions examined by magnetic resonance imaging was detected. After 6 weeks of Mn exposure, neurobehavioral deficits in an open field test, a grip strength test, and a forced swim test were observed. Eight weeks of Mn exposure increased striatal 5-hydroxyindoleacetic acid (a serotonin metabolite) levels, but did not alter the levels of striatal dopamine, its metabolites and serotonin. Krishna et al. also reported significant increases in mRNA levels of GFAP (an astrocyte activation marker), HO-1 (an oxidative stress marker) and NOS2 (a nitrosative stress marker), and in protein expression level of GFAP in the substantia nigra pars reticulata after 8 weeks of Mn exposure. These results suggest that 400,000 µg/L Mn exposure via drinking water in mice induces neurobehavioral deficits, serotonergic imbalance, and glial activation accompanied by an increase in brain Mn deposition. The report by Krishna et al. is interesting because the studies on the neurobehavioral effect of Mn exposure by drinking water in mice are very limited. However, Mn concentrations previously reported in well drinking water (Agusa et al. in Vietnam Environ Pollut 139(1):95-106, 2006; Buschmann et al. in Environ Int 34(6):756-764, 2008; Hafeman et al. in Environ Health Perspect 115(7):1107-1112, 2007; Wasserman et al. in Bangladesh Environ Health Perspect 114(1):124-129, 2006) were lower than 400,000 µg/L.


Assuntos
Encéfalo/efeitos dos fármacos , Manganês/toxicidade , Síndromes Neurotóxicas/patologia , Animais , Masculino
17.
Am J Neurodegener Dis ; 3(3): 134-42, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25628964

RESUMO

Aging is a major risk factor for Alzheimer's disease (AD). Aggregation of amyloid beta (Aß) in cerebral cortex and hippocampus is a hallmark of AD. Many factors have been identified as causative elements for onset and progression of AD; for instance, tau seems to mediate the neuronal toxicity of Aß, and downregulation of macroautophagy (autophagy) is thought to be a causative element of AD pathology. Expression of autophagy-related genes is reduced with age, which leads to increases in oxidative stress and aberrant protein accumulation. In this study, we found that expression of the autophagy-related genes atg1, atg8a, and atg18 in Drosophila melanogaster was regulated with aging as well as their own activities. In addition, the level of atg18 was maintained by dfoxo (foxo) and dsir2 (sir2) activities in concert with aging. These results indicate that some autophagy-related gene expression is regulated by foxo/sir2-mediated aging processes. We further found that reduced autophagy activity correlated with late-onset neuronal dysfunction caused by neuronal induction of Aß. These data support the idea that age-related dysfunction of autophagy is a causative element in onset and progression of AD.

18.
Dev Growth Differ ; 49(9): 711-9, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17908182

RESUMO

Bone morphogenetic proteins (BMPs) are known to play roles in inner ear development of higher vertebrates. In zebrafish, there are several reports showing that members of the BMP family are expressed in the otic vesicle. We have isolated a novel zebrafish mutant gallery, which affects the development of the semicircular canal. Gallery merely forms the lateral and the immature anterior protrusion, and does not form posterior and ventral protrusions. We found that the expression of bmp2b and bmp4, both expressed in the normal optic vesicle at the protrusion stage, are extremely upregulated in the otic vesicle of gallery. To elucidate the role of BMPs in the development of the inner ear of zebrafish, we have applied excess BMP to the wild-type otic vesicle. The formation of protrusions was severely affected, and in some cases, they were completely lost in BMP4-treated embryos. Furthermore, the protrusions in gallery treated with Noggin were partially rescued. These data indicate that BMP4 plays an important role in the development of protrusions to form semicircular canals.


Assuntos
Proteínas Morfogenéticas Ósseas/fisiologia , Canais Semicirculares/embriologia , Proteínas de Peixe-Zebra/fisiologia , Peixe-Zebra/embriologia , Actinas/metabolismo , Animais , Padronização Corporal/efeitos dos fármacos , Proteína Morfogenética Óssea 2 , Proteína Morfogenética Óssea 4 , Proteínas Morfogenéticas Ósseas/genética , Proteínas Morfogenéticas Ósseas/metabolismo , Proteínas de Transporte/farmacologia , Orelha Interna/efeitos dos fármacos , Orelha Interna/embriologia , Orelha Interna/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Hibridização In Situ , Camundongos , Microscopia Confocal , Fenótipo , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia , Canais Semicirculares/efeitos dos fármacos , Canais Semicirculares/metabolismo , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/fisiologia , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
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