RESUMEN
The aim of this study was to elucidate the signaling pathway involved in the anti-aging effect of erythropoietin (EPO) and to clarify whether recombinant human EPO (rhEPO) affects apoptosis in the aging rat hippocampus by upregulating Sirtuin 1 (SIRT1). In this study, a rat model of aging was established using D-galactose. Behavioral changes were monitored by the Morris water maze test. Using immunohistochemistry, we studied the expression of SIRT1, B-cell lymphoma/leukemia-2 gene (Bcl-2), and Bcl-2 associated X protein (Bax) expression, and apoptotic cells in the hippocampus of a rat model of aging in which rhEPO was intraperitoneally injected. The escape latency in rats from the EPO group shortened significantly; however, the number of platform passes increased significantly from that in the D-gal group (P < 0.05). Compared to the D-gal group, in the EPO group, the number of SIRT1 and Bcl-2-positive cells increased (P < 0.05), but the number of Bax-positive cells and apoptotic cells decreased in the hippocampus of aging rats (P < 0.05). These results suggest that rhEPO regulates apoptosis-related genes and affects apoptosis in the hippocampus of aging rats by upregulating SIRT. This may be one of the important pathways underlying the anti-aging property of EPO.
Asunto(s)
Envejecimiento , Apoptosis/efectos de los fármacos , Eritropoyetina/farmacología , Hipocampo/efectos de los fármacos , Sirtuina 1/metabolismo , Factores de Edad , Envejecimiento/metabolismo , Envejecimiento/patología , Envejecimiento/psicología , Animales , Conducta Animal/efectos de los fármacos , Galactosa/farmacología , Hipocampo/enzimología , Hipocampo/patología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas Sprague-Dawley , Proteínas Recombinantes/farmacología , Transducción de Señal/efectos de los fármacos , Proteína X Asociada a bcl-2/metabolismoRESUMEN
OBJECTIVE: To investigate the effect of Helicobacter pylori (Hp) on platelet activation and coagulation function in patients with acute cerebral infarction. METHODS: Sixty-six patients with acute cerebral infarction and 50 health individuals were enrolled in the study. Hp antibody,expression of CD62p on platelets and clotting indexes were measured and compared between two groups. RESULTS: The positive rate of Hp-IgG and Hp-CagA in cerebral infarction patients were higher than that in controls (P<0.05). The positive rate of CD62p in patients with positive Hp-IgG and Hp-CagA was significantly higher than that in negative patients and also controls (P<0.05). The APTT and TT were lower and FIB was higher in patients with positive Hp antibody than those in patients with negative Hp antibody (P<0.05),but there was no difference in PT,PTR and INR (P>0.05). CONCLUSION: Hp infection can activate platelets and affect coagulation function,which may be involved in the development of cerebral infarction.
Asunto(s)
Coagulación Sanguínea , Infarto Cerebral/sangre , Infecciones por Helicobacter/sangre , Activación Plaquetaria , Adulto , Anciano , Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos/metabolismo , Proteínas Bacterianas/metabolismo , Estudios de Casos y Controles , Infarto Cerebral/microbiología , Femenino , Infecciones por Helicobacter/complicaciones , Helicobacter pylori/metabolismo , Helicobacter pylori/patogenicidad , Humanos , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Selectina-P/sangreRESUMEN
LAPTM4B-35, encoded by Lysosomal protein transmembrane 4 beta (LAPTM4B) is over-expressed in more than 71% of hepatocellular carcinomas (HCCs) and associated with prognosis of the patients. But the exact role and molecular mechanism in HCC have not been determined. In this study, we explored the effects and mechanisms of LAPTM4B-35 on tumor growth and metastasis in vitro and in vivo by overexpression and depletion of LAPTM4B in HCC HepG2 and Bel7402 cells. These findings suggest that overexpression of LAPTM4B-35 plays a critical role in the growth and metastasis of HCC, and LAPTM4B-35 may therefore be a therapeutic target for HCC.
Asunto(s)
Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Proteínas de la Membrana/biosíntesis , Proteínas Oncogénicas/biosíntesis , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Carcinoma Hepatocelular/genética , Ciclo Celular/genética , Procesos de Crecimiento Celular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Doxorrubicina/antagonistas & inhibidores , Doxorrubicina/farmacología , Humanos , Neoplasias Hepáticas/genética , Proteínas de la Membrana/genética , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Metástasis de la Neoplasia , Proteína Oncogénica v-akt/metabolismo , Proteínas Oncogénicas/genética , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/genética , Transducción de Señal , Transfección , Regulación hacia Arriba , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Lysosomal protein transmembrane 4 beta (LAPTM4B) was originally identified as a hepatocellular carcinoma (HCC)-associated gene. This gene and its protein product LAPTM4B-35, are both overexpressed in a variety of human cancers. However, its specific role in cell transformation and malignancy has remained elusive. In the present study we investigated the effects of LAPTM4B-35 overexpression on the malignant phenotypic features in the HLE cell line. Our data show that overexpression of LAPTM4B-35 promotes cell proliferation, exogenous growth-stimulating factor-independent and anchorage-independent growth, and enhances metastatic potential, including promotion of both cell migration and invasion. Study of the underlying mechanisms demonstrated alterations of molecular events involved in these processes, which included upregulation of proliferation-promoting transcription factors such as c-Myc, c-Jun, and c-Fos, and cell cycle-promoting proteins such as cyclin D1 and cyclin E. In addition, mutagenesis study showed that the PPRP motif in the N-terminal region of LAPTM4B-35 plays a critical role in promoting proliferation, migration, and invasion, as well as in the upregulation of the oncoproteins noted above. These data offer insight into the mechanism by which this novel tetratransmembrane protein contributes to the pathogenesis of liver cancer, and suggest that it may be a potential target for cancer therapy.
Asunto(s)
Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Proteínas de la Membrana/fisiología , Proteínas Oncogénicas/fisiología , Anciano , Secuencias de Aminoácidos , Línea Celular Tumoral , Proliferación Celular , Humanos , Proteínas de la Membrana/química , Metástasis de la Neoplasia , Proteínas Oncogénicas/química , Proteínas Proto-Oncogénicas c-fos/fisiología , Proteínas Proto-Oncogénicas c-myc/fisiologíaRESUMEN
The exposure of Sciaenops ocellatus to monocrotophos at its concentration of 0.25, 0.5, 1.0 or 2.0 mg L-1 for 4 days demonstrated that under the stress of low concentration (0.25 mg.L-1) monocrotophos, the chloride cells of branchiae proliferated, accompanied with the increase of Na+/K(+)-ATPase activity, while under high concentrations of monocrotophos, the damage of gill was much heavier, and the Na+/K(+)-ATPase activity also decreased. The damage in gill under sublethal monocrotophos exposure included hypertrophy and edema, and thus, the lamellar epithelium became thick and lifting, and the lamellae were bulbing or fusing. The ultramicrostructural changes of the gill of the exposure fish were the swollen and even rupture of rER, mitochondria, microtubule and nuclear membrane.