RESUMEN
Pinch-3 protein is an important constituent of cell membranes, which directly affects the cell morphology and mechanical properties. We observed and compared the change of morphology and cell traction force of glomerular podocytes before and after Pinch-3 gene inhibition by gene interference technology in this experiment. We found that a number of pores appeared on the cell surface, and the cell projected area were increased at the same time, with an approximate average about an increase of 40% after Pinch-3 gene inhibition. The results showed that the cell traction force of glomerular podocytes was significantly reduced, with an approximate average decrease of 40%, the maximum value of the cell traction force was reduced and the distribution of cell traction force became dispersive. All this suggested that after Pinch-3 gene inhibition, some pores created on the cell surface influenced the physical properties of glomerular podocytes and then affected the cell projected area and influenced the formation and distribution of cell traction force of the glomerular podocytes as well.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Movimiento Celular , Proteínas con Dominio LIM/genética , Mecanotransducción Celular/fisiología , Podocitos/citología , Proteínas Adaptadoras Transductoras de Señales/fisiología , Fenómenos Biomecánicos , Ingeniería Genética , Humanos , Glomérulos Renales/citología , Proteínas con Dominio LIM/fisiología , Proteínas de la Membrana/genética , Proteínas de la Membrana/fisiología , Podocitos/fisiología , Estrés MecánicoRESUMEN
The effect of betanin on a rat paraquat-induced acute lung injury (ALI) model was investigated. Paraquat was injected intraperitoneally at a single dose of 20 mg/kg body weight, and betanin (25 and 100 mg/kg/d) was orally administered 3 days before and 2 days after paraquat administration. Rats were sacrificed 24 hours after the last betanin dosage, and lung tissue and bronchoalveolar lavage fluid (BALF) were collected. In rats treated only with paraquat, extensive lung injury characteristic of ALI was observed, including histological changes, elevation of lung : body weight ratio, increased lung permeability, increased lung neutrophilia infiltration, increased malondialdehyde (MDA) and myeloperoxidase (MPO) activity, reduced superoxide dismutase (SOD) activity, reduced claudin-4 and zonula occluden-1 protein levels, increased BALF interleukin (IL-1) and tumor necrosis factor (TNF)-α levels, reduced BALF IL-10 levels, and increased lung nuclear factor kappa (NF-κB) activity. In rats treated with betanin, paraquat-induced ALI was attenuated in a dose-dependent manner. In conclusion, our results indicate that betanin attenuates paraquat-induced ALI possibly via antioxidant and anti-inflammatory mechanisms. Thus, the potential for using betanin as an auxilliary therapy for ALI should be explored further.
Asunto(s)
Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Antioxidantes/farmacología , Betacianinas/farmacología , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Paraquat/farmacología , Lesión Pulmonar Aguda/metabolismo , Animales , Antiinflamatorios/farmacología , Líquido del Lavado Bronquioalveolar/química , Claudina-4/metabolismo , Interleucina-1/metabolismo , Interleucina-10/metabolismo , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Enfermedades Pulmonares Intersticiales/metabolismo , Masculino , Malondialdehído/metabolismo , FN-kappa B/metabolismo , Infiltración Neutrófila/efectos de los fármacos , Permeabilidad/efectos de los fármacos , Peroxidasa/metabolismo , Ratas , Ratas Sprague-Dawley , Superóxido Dismutasa/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Proteína de la Zonula Occludens-1/metabolismoRESUMEN
BACKGROUND: Ixeris sonchifolia (Bge.) Hance is an herbal medication used in China as an analgesic. METHODS: The effect of six flavonoid compounds isolated from Ixeris sonchifolia (Bge.) Hance on stimulus-induced superoxide generation and phosphorylation of tyrosine residues of protein in human neutrophils was investigated. The six compounds examined were luteolin 7-glucuronide methylester (LGME), luteolin 7-glucuronide ethylester (LGEE), luteolin 7-glucoside (LG), luteolin 7-glucopyranosyl-(1-->6)-glucoside (LGG6), luteolin 7-glucopyranosyl-(1-->2)-glucoside (LGG2) and apigenin 7-glucoside (AG). RESULTS: When the cells were preincubated with these six flavonoids, the superoxide generation induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) was significantly suppressed in a concentration-dependent manner. These flavonoids also suppressed the superoxide generation induced by arachidonic acid (AA). The rate of suppression by these flavonoids was AG>LG, LGG6, LGEE, LGG2>LGME. In case of the superoxide generation induced by phorbol 12-myristate 13-acetate (PMA), LG, LGG6 and AG suppressed the superoxide generation but LGME, LGEE and LGG2 gave no effect. When the cells were incubated with fMLP in the presence of LGME, LGEE and AG, fMLP-induced tyrosyl phosphorylation of 45-kDa proteins of the cells was dose-dependently suppressed in parallel to the suppression of fMLP-induced superoxide generation. CONCLUSION: Flavonoids suppress tyrosine phosphorylase in a dose-dependent manner, and may have pharmacoceutical applications.