RESUMO
Analyses of supernatants from apoptotic cells have helped in the identification of many signals that modulate the states of cell activation and differentiation. However, the current knowledge about the soluble factors that are released during apoptosis is rather limited. Previous studies have shown that S5a and angiocidin (both encoded by PSMD4) induce human acute monocytic leukemia cells (THP-1 cells) to differentiate into macrophages, but the cell-surface receptor of S5a has not been identified. In this study, we show that apoptotic THP-1 cells release endogenous S5a that binds to death receptor-6 (DR6, also known as TNFRSF1), which was identified as an orphan receptor, to induce THP-1 cells to differentiate. Furthermore, we found that the NF-κB pathway is activated, and that the transcription factors WT1 (Wilms' tumor 1) and c-myb mediate S5a-induced THP-1 differentiation. We also show that differentiation is blocked by anti-DR6 antibody, DR6 siRNA, DR6-Fc, NF-κB inhibitor or WT1 siRNA treatment. Our findings indicate that the interaction between cells can determine their differentiation, and we provide evidence for a functional interaction between S5a and DR6, which provides a novel potential mechanism to induce the differentiation of cancer cells, especially during biotherapy for leukemia.
Assuntos
Monócitos/fisiologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas Proto-Oncogênicas c-myb/metabolismo , Receptores do Fator de Necrose Tumoral/metabolismo , Proteínas WT1/metabolismo , Anticorpos Bloqueadores/farmacologia , Apoptose/genética , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Linhagem Celular , Humanos , NF-kappa B/metabolismo , Fosforilação/genética , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/genética , Proteínas Proto-Oncogênicas c-myb/genética , RNA Interferente Pequeno/genética , Proteínas de Ligação a RNA , Receptores do Fator de Necrose Tumoral/genética , Receptores do Fator de Necrose Tumoral/imunologia , Transdução de Sinais/genética , Proteínas WT1/genéticaRESUMO
As an important carrier of human activities, the spatial type of land use has an important impact on the surface water environment. Taking the Ruoergai wetland as an example, based on object-oriented remote sensing interpretation of land use types combined with water quality examination data, this study analyzed the impact and driving mechanism of land use types at different scales on the surface water environment at the small watershed and buffer scale. â It was found that the water quality of the Ruoergai wetland could been classified as water grade V, and it was slightly eutrophic as a whole. The main pollutants were total nitrogen(TN) and phosphorus(TP), and the pollution originated from domestic sewage and grazing. â¡ The environmental quality of surface water was closely related to land use types. There was a negative correlation between chemical oxygen demand(COD) and the proportion of water area, a positive correlation between TN and the proportion of swamp area, and a negative correlation between total TP. ⢠There was a significant correlation between spatial land use types at different scales and surface water environment. The land use type within a buffer of 1000 m had the highest interpretation degree for all factors, the land use type within a buffer of 200 m had the greatest interpretation degree for COD, the land use type within a buffer of 500 m zone had the greatest interpretation degree for TP and TN, and the land use type within a buffer of 800 m had the greatest explanation for Chl-a. The results of this study showed that the Ruoergai wetland wetland had a certain purification effect on pollutants and eutrophication. However, different land use types had different effects on different pollutants. The water body had a purification effect on Fe2+, COD, and Chl-a, and the swamp had a purification effect on TP but a cumulative effect on TN. Thus, the small-buffer zone(≤ 1000 m) land use type should be controlled, the water body and swamp areas should be controlled, the self-purification capacity of wetland waters should be improved, and the surface water environment of the Ruoergai wetland should be further protected and repaired.
Assuntos
Poluentes Ambientais , Qualidade da Água , Humanos , Nitrogênio/análise , Fósforo/análise , Áreas AlagadasRESUMO
AIMS: Obestatin regulates water metabolism by inhibiting arginine vasopressin (AVP) release and upregulated obestatin has been detected in patients with chronic heart failure (CHF). However, the significance of obestatin in CHF, particularly with regard to water retention and aquaporin 2 (AQP2) expression, remains unknown. MAIN METHODS: Using a CHF rat model, the effects of 2-week exogenous obestatin administration were evaluated. Expression of AQP2 was evaluated by immunoblotting, immunohistochemical staining, and quantitative real-time PCR (qPCR) in CHF rat model and mouse inner medullary collecting duct (mIMCD) 3 cell line. Moreover, the influence of obestatin on the genetic transcription profile in mIMCD3 cells was evaluated by microarray, and the potential regulatory mechanisms of obestatin on AQP2 were evaluated by RNA silencing of vasopressin receptor 2 (V2R), peroxisome proliferator-activated receptor gamma (PPARG), and G protein-coupled receptor 39 (GPR39). KEY FINDINGS: Obestatin increased urinary output and improved expression of CHF biomarker without significantly altering cardiac function, plasma electrolyte concentrations, or the plasma AVP concentration. AQP2 expression was significantly reduced. The results of microarray analyses and qPCR indicated that mRNA levels of Aqp2, Pparg, and V2r were significantly decreased. Inhibition of V2r and Pparg mRNA further reduced the expression of AQP2, while the inhibitory efficacy of obestatin on AQP2 was significantly offset after Gpr39 knockdown. SIGNIFICANCE: Long-term treatment with obestatin improves water retention in CHF by increasing urinary output through downregulation of AQP2 expression in renal IMCD cells. These effects may be at least partially mediated by regulation of GPR39, V2R and PPARG signaling.
Assuntos
Edema/tratamento farmacológico , Grelina/farmacologia , Insuficiência Cardíaca/metabolismo , PPAR gama/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Vasopressinas/metabolismo , Animais , Aquaporina 2/metabolismo , Arginina Vasopressina , Água Corporal , Linhagem Celular , Edema/metabolismo , Insuficiência Cardíaca/fisiopatologia , Rim/efeitos dos fármacos , Rim/metabolismo , Túbulos Renais Coletores/metabolismo , Masculino , Camundongos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Equilíbrio Hidroeletrolítico , Desequilíbrio HidroeletrolíticoRESUMO
ARE-mRNAs are actively degraded with tristetraprolin (TTP) in resting cells while they turn into stable messengers in activated cells. P38 plays a crucial role in stabilizing ARE-mRNA. Here we reveal that P38 activation represses the interaction between TTP and Ago2, thus restraining TTP from being targeted into processing bodies and stabilizing ARE-mRNA.
Assuntos
Elementos Ricos em Adenilato e Uridilato , Proteínas Argonautas/metabolismo , Estabilidade de RNA , RNA Mensageiro/genética , Tristetraprolina/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Regiões 3' não Traduzidas , Proteínas Argonautas/genética , Regulação da Expressão Gênica , Células HEK293 , Células HeLa , Humanos , Lipopolissacarídeos/farmacologia , Fosforilação , Transcrição Gênica/efeitos dos fármacos , Tristetraprolina/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Ethanol has been reported to have toxicity on embryonic stem cells (ESCs). The present study aims to address the teratogenic effects of ethanol on the growth and cardiac differentiation of ESCs. Mouse embryonic stem D3 cells were employed. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays were used to determine cytotoxicity. Quantitative real time polymerase chain reaction (qRT-PCR) and Western blotting were used to analyze the expressions of cardiac differentiation-related and Wnt signaling factors. The beating profile of cardiomyocytes was recorded to assess cardiac differentiation. Ethanol induced growth inhibition in both undifferentiated and differentiated ESCs after 5 days of exposure. Ethanol inhibited the loss of pluripotent gene expressions including Nanog, Sox2 and Oct4. The expressions of cardiac markers, Nkx2.5, Mef2c, Tbx5, dHand, αMHC, Cx43 and troponin C1, were suppressed by ethanol treatment. Furthermore, ethanol delayed cardiac differentiation of ESCs till 11 days of differentiation. The expressions of Wnt-related regulators, ß-catenin and its target cyclin D1, were downregulated by ethanol. Wnt pathway agonist wnt3a could greatly rescue ethanol-induced inhibition of cardiac differentiation and Wnt-pathway-related protein expressions. These finding suggested that ethanol suppresses mouse ESC differentiation largely by inhibiting Wnt signaling pathway.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Etanol/toxicidade , Células-Tronco Embrionárias Murinas/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Diferenciação Celular/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células Cultivadas , Relação Dose-Resposta a Droga , Camundongos , Células-Tronco Embrionárias Murinas/fisiologia , Via de Sinalização Wnt/fisiologiaRESUMO
Reports of clinical cases with Auer bodies in the plasma cells in multiple myeloma (MM) are rare; however, most of those reported contain peroxidase (POX)-negative Auer bodies rather than the POX-positive Auer bodies observed in myeloid progenitors, indicating differences in their chemical properties. Furthermore, the cases with POX-positive Auer bodies similar to those observed in myeloid cells are extremely rare in non-myeloid cells. Here, we report the clinical features, laboratory investigations, diagnosis and treatment of a case of MM with POX-positive Auer bodies in plasma cells and review related the literature to advance the prognostic evaluation, diagnosis and treatment of similar cases.