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Nitric oxide production is associated to increased lipoperoxidation and active caspase-3 in demyelinated brain regions of the taiep rat

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Advances in Bioscience and Biotechnology 2012年第6期3卷 695-704页

作者： Guadalupe soto-Rodríguez Daniel Martínez-Fong Rosa Arroyo Patricia Aguilar-Alonso Hector Rubio José Ramón Eguibar Araceli Ugarte maricela torres-soto Juan Antonio González-Barrios Jorge Cebada Eduardo Brambila Bertha Alicia Leon-Chavez Departamento de Fisiología Biofísica y Neurociencias Cinvestav Apdo. Postal 14-740 México D.F. 07000 México División de Medicina Genómica del Hospital regional 1o de Octubre ISSSTE Avenida Instituto Politécnico Nacional 1669 México D. F. 07760 México Escuela de Biología BUAP Puebla Pue. Mexico Facultad de Ciencias Químicas BUAP 14 sur y Av. Edif. 138 San Claudio 72570 Puebla Pue. México Facultad de Medicina Universidad Autónoma de Yucatán Mexico Instituto de Fisiología BUAP 14 sur 6301 Puebla Pue. México

We previously showed that the increase in nitric oxide (NO) levels and NO synthase (NOS) expression correlate with the progression of reactive astrocytosis and demyelination in the brains of 6-month-old taiep rats. Increased levels of NO can result in high concentration of peroxynitrite and thus cause tissue damage, which consists of lipoperoxidation of the cytoplasmic membrane, such as the myelin, and of apoptotic and necrotic cell-death. On this basis, we studied whether the increased NO production is associated with lipoperoxidation and cell death in the cerebellum and brainstem over the age (1, 3, 6, and 8 months) of taiep rats. The results were compared with those obtained in matched Sprague-Dawley (SD) rats. We measured the levels of nitrites (NO production), malonyldialdehyde, and 4-hydroxyalkenal (lipoperoxidation) in brain tissue homogenates. The three NOS isoforms and cleaved caspase-3 were evaluated by using ELISA and immunostaining techniques. Our results showed that NO production and lipoperoxidation increased in the cerebellum and brainstem as the age of the taiep rats increased compared to SD rats. The overexpression of nNOS and iNOS were in the Purkinje cells, magnocellular neurons, and in oligodendrocytes, whereas the glial cells showed strong cleaved-caspase-3 immunoreactivity. In summary our results suggest that NO plays a role in the demyelination and cell death in the taiep rat.

关键词： Hypomyelination Nitrite Malonyldialdehyde Apoptosis Necrosis

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TNF system in eutopic endometrium from women with endometriosis

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Open Journal of Obstetrics and Gynecology 2013年第2期3卷 271-278页

作者： María Angélica Boric Marisa torres Claudio Pinto maricela Pino Paulina Hidalgo Fernando Gabler Ariel Fuentes María Cecilia Johnson Institute of Maternal and Child Research Faculty of Medicine University of Chile Santiago Chile

The role of the tumor necrosis factor (TNF) system in endometriosis is not completely clear and therefore was the focus of this study. In eutopic endometria obtained from women with (n = 41) and without (controls;n = 34) endometriosis during laparoscopy, the subcellular location and the percentages for TNF, TNFR1, TNFR2 and CD45 positive-cells were determined (immunohistochemistry);the protein concentration (ELISA) of the soluble receptors (sTNFR1 and sTNFR2) were measured in 4h-explants culture media and the TNF concentration was performed in ex vivo endometrial homogenates. The TNF, TNFR1 and TNFR2 mRNAs were analyzed by real-time PCR. In control endometria, TNF, TNFR1 and sTNFR1 proteins increased during the late secretory phase. In endometriosis endometria, the protein highest level of TNFR1 was reached during the early and the mid secretory phases and of sTNFR1 concentration during the proliferative phase;however, during the late secretory phase, both TNFR1 and sTNFR1 protein levels were reduced compared to the control endometria (p sTNFR2 concentrations, and TNF and TNFR2 mRNAs were similar in control and endometriosis endometria. Although TNFR1 mRNA was highly expressed, no significant differences were found between control and endometriosis endometria. In summary, this study establishes that TNF and TNFR1 protein expressions and the sTNFR concentrations in eutopic endometria from women with and without endometriosis are dependent on the menstrual cycle. The differences on the TNFR1 and sTNFR1 protein pattern between both groups, mainly during the mid and late secretory phases may play a role in the lower implantation rates observed in women with endometriosis, and also could be related to the altered cell death, which favor the augmented cell viability facilitating the characteristic endometrial implantation and growth outside the uterus in this disease.

关键词： Endometriosis Eutopic Endometrium TNF sTNFR1 sTNFR2

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