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2 results on '"Bosch-Morato, M"'

1. Methylglyoxal Produced by Amyloid-beta Peptide-Induced Nitrotyrosination of Triosephosphate Isomerase Triggers Neuronal Death in Alzheimer's Disease

Author

Tajes, M, Eraso-Pichot, A, Rubio-Moscardo, F, Guivernau, B, Ramos-Fernandez, E, Bosch-Morato, M, Guix, FX, Clarimon, J, Miscione, GP, Boada, M, Gil-Gomez, G, Suzuki, T, Molina, H, Villa-Freixa, J, Vicente, R, and Munoz, FJ

Subjects
3-nitrotyrosine, apoptosis, methylglyoxal, amyloid, Alzheimer's disease, triose-phosphate isomerase
Abstract

Amyloid-beta peptide (A beta) aggregates induce nitro-oxidative stress, contributing to the characteristic neurodegeneration found in Alzheimer's disease (AD). One of the most strongly nitrotyrosinated proteins in AD is the triosephosphate isomerase (TPI) enzyme which regulates glycolytic flow, and its efficiency decreased when it is nitrotyrosinated. The main aims of this study were to analyze the impact of TPI nitrotyrosination on cell viability and to identify the mechanism behind this effect. In human neuroblastoma cells (SH-SY5Y), we evaluated the effects of A beta(42) oligomers on TPI nitrotyrosination. We found an increased production of methylglyoxal (MG), a toxic byproduct of the inefficient nitro-TPI function. The proapoptotic effects of A beta(42) oligomers, such as decreasing the protective Bcl2 and increasing the proapoptotic caspase-3 and Bax, were prevented with a MG chelator. Moreover, we used a double mutant TPI (Y165F and Y209F) to mimic nitrosative modifications due to A beta action. Neuroblastoma cells transfected with the double mutant TPI consistently triggered MG production and a decrease in cell viability due to apoptotic mechanisms. Our data show for the first time that MG is playing a key role in the neuronal death induced by A beta oligomers. This occurs because of TPI nitrotyrosination, which affects both tyrosines associated with the catalytic center.

Published
2014

2. Nitro-Oxidative Stress after Neuronal Ischemia Induces Protein Nitrotyrosination and Cell Death

Author

Tajes, M, Ill-Raga, G, Palomer, E, Ramos-Fernandez, E, Guix, FX, Bosch-Morato, M, Guivernau, B, Jimenez-Conde, J, Ois, A, Perez-Asensio, F, Reyes-Navarro, M, Caballo, C, Galan, AM, Alameda, F, Escolar, G, Opazo, C, Planas, A, Roquer, J, Valverde, MA, Munoz, FJ, Tajes, M, Ill-Raga, G, Palomer, E, Ramos-Fernandez, E, Guix, FX, Bosch-Morato, M, Guivernau, B, Jimenez-Conde, J, Ois, A, Perez-Asensio, F, Reyes-Navarro, M, Caballo, C, Galan, AM, Alameda, F, Escolar, G, Opazo, C, Planas, A, Roquer, J, Valverde, MA, and Munoz, FJ

Abstract

Ischemic stroke is an acute vascular event that obstructs blood supply to the brain, producing irreversible damage that affects neurons but also glial and brain vessel cells. Immediately after the stroke, the ischemic tissue produces nitric oxide (NO) to recover blood perfusion but also produces superoxide anion. These compounds interact, producing peroxynitrite, which irreversibly nitrates protein tyrosines. The present study measured NO production in a human neuroblastoma (SH-SY5Y), a murine glial (BV2), a human endothelial cell line (HUVEC), and in primary cultures of human cerebral myocytes (HC-VSMCs) after experimental ischemia in vitro. Neuronal, endothelial, and inducible NO synthase (NOS) expression was also studied up to 24 h after ischemia, showing a different time course depending on the NOS type and the cells studied. Finally, we carried out cell viability experiments on SH-SY5Y cells with H2O2, a prooxidant agent, and with a NO donor to mimic ischemic conditions. We found that both compounds were highly toxic when they interacted, producing peroxynitrite. We obtained similar results when all cells were challenged with peroxynitrite. Our data suggest that peroxynitrite induces cell death and is a very harmful agent in brain ischemia.

Published
2013

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