Browsing by Author "Fernández, V"

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    PC12 and neuro 2a cells have different susceptibilities to acetylcholinesterase-amyloid complexes, amyloid25-35 fragment, glutamate, and hydrogen peroxide
    (1999) Calderón, FH; Bonnefont, A; Muñoz, FJ; Fernández, V; Videla, LA; Inestrosa, NC
    This work addresses the differential effects of several oxidative insults on two neuronal cell lines, PC12 and Neuro 2a cells, extensively used as neuronal models in vitro, We measured cellular damage using the cytotoxic assays for MTT reduction and LDH release and found that acetylcholinesterase (AChE)-amyloid-beta-peptide (AP) complexes, A beta(25-35) fragment, glutamate and H2O2 were over 200-fold more toxic to PC12 than to Neuro 2a cells, 17 alpha and 17 beta estradiol were able to protect both cell types from damage caused by H2O2 or glutamate, By contrast, other insults not related to oxidative stress, such as those caused by the nonionic detergent Triton X-100 and serum deprivation, induced a similar level of damage in both PC12 and Neuro 2a cells, Considering that the AP peptide, H2O2 and glutamate are cellular insults that cause an increase In reactive oxygen species (ROS), the intracellular levels of the antioxidant compound, glutathione were verified, Neuro 2a cells were found to have 4- to 5-fold more glutathione than PC12 cells, Our results suggest that Neuro 2a cells are less susceptible to exposure to AChE-A beta complexes, A beta(25-35) fragment, glutamate and H2O2 than PC12 cells, due to higher intracellular levels of antioxidant defense factors. (C) 1999 Wiley-Liss, Inc.
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    Vitamin E but not 17β-estradiol protects against vascular toxicity induced by β-amyloid wild type and the Dutch amyloid variant
    (2002) Muñoz, FJ; Opazo, C; Gil-Gómez, G; Tapia, G; Fernández, V; Valverde, MA; Inestrosa, NC
    Amyloid beta-peptide (Abeta) fibril deposition on cerebral vessels produces cerebral amyloid angiopathy that appears in the majority of Alzheimer's disease patients. An early onset of a cerebral amyloid angiopathy variant called hereditary cerebral hemorrhage with amyloidosis of the Dutch type is caused by a point mutation in Abeta yielding Abeta(Glu22-->Gln). The present study addresses the effect of amyloid fibrils from both wild-type and mutated Abeta on vascular cells, as well as the putative protective role of antioxidants on amyloid angiopathy. For this purpose, we studied the cytotoxicity induced by Abeta(1-40 Glu22-->Gln) and Abeta(1-40 wild-type) fibrils on human venule endothelial cells and rat aorta smooth muscle cells. We observed that Abeta(Glu22-->Gln) fibrils are more toxic for vascular cells than the wild-type fibrils. We also evaluated the cytotoxicity of Abeta fibrils bound with acetylcholinesterase (AChE), a common component of amyloid deposits. Abeta(1-40 wild-type)-AChE fibrillar complexes, similar to neuronal cells, resulted in an increased toxicity on vascular cells. Previous reports showing that antioxidants are able to reduce the toxicity of Abeta fibrils on neuronal cells prompted us to test the effect of vitamin E, vitamin C, and 17beta-estradiol on vascular damage induced by Abeta(wild-type) and Abeta(Glu22-->Gln). Our data indicate that vitamin E attenuated significantly the Abeta-mediated cytotoxicity on vascular cells, although 17beta-estradiol and vitamin C failed to inhibit the cytotoxicity induced by Abeta fibrils.