Glutamate excitotoxicity activates the MAPK/ERK signaling pathway and induces the survival of rat hippocampal neurons in vivo

Abstract

The aim of this study was to determine how gossypol affects the viability and activity of polymorphonuclear leukocytes and monocytes in blood obtained from healthy donors. Loss of mitochondrial membrane potential (??m) and apoptosis was maximized in human polymorphonuclear leukocytes and monocytes after incubation with gossypol. Pretreatment with a caspase-9 inhibitor or antioxidants (superoxide dismutase or Trolox) inhibited gossypol-induced loss of the ??m and apoptosis. Likewise, we observed participation of caspase -3, -7, and -10 in gossypol-induced apoptosis. Expression of the proapoptotic genes bax, bak, bad and p53/Tp53 increased in polymorphonuclear leukocytes exposed to gossypol. The expression of the anti-apoptotic genes bcl- XL and mcl-1 was reduced when polymorphonuclear leukocytes and monocytes were treated with gossypol. Gossypol treatment also inhibited yeast phagocytosis by these cells. We concluded that gossypol induces apoptosis in phagocytic cells and that this effect was dose-dependent. The findings in this report may be important to consider in light of possible gossypol use in clinical strategies for cancer treatment. " 2009 Informa UK Ltd.",,,,,,"10.1080/08923970902718049",,,"http://hdl.handle.net/20.500.12104/41787","http://www.scopus.com/inward/record.url?eid=2-s2.0-70350680559&partnerID=40&md5=0a2363ef2952cde7785a4e10d67af7db",,,,,,"2",,"Immunopharmacology and Immunotoxicology",,"320

330",,"31",,"Scopus

WOS",,,,,,"Apoptosis; Caspases; Gossypol; Monocyte; Phagocytosis; Polymorphonuclear leukocyte; Reactive oxygen species",,,,,,"Gossypol induced apoptosis of polymorphonuclear leukocytes and monocytes: Involvement of mitochondrial pathway and reactive oxygen species",,"Article" "43587","123456789/35008",,"Pimienta, E., Departamento de Ecología, Ctro. de Cie. Biol. y Agropecuarias, Universidad de Guadalajara, Las Agujas, Zapopan, Jalisco, 45110, Mexico; Hernandez, G., Departamento de Ecología, Ctro. de Cie. Biol. y Agropecuarias, Universidad de Guadalajara, Las Agujas, Zapopan, Jalisco, 45110, Mexico; Domingues, A., Departamento de Ecología, Ctro. de Cie. Biol. y Agropecuarias, Universidad de Guadalajara, Las Agujas, Zapopan, Jalisco, 45110, Mexico; Nobel, P.S., Department of Biology, University of California, Los Angeles, CA 90095-1606, United States",,"Pimienta, E.

Hernandez, G.

Domingues, A.

Nobel, P.S.",,"1998",,"In Stenocereus queretaroensis (Weber) Buxbaum, an arborescent cactus cultivated in Jalisco, Mexico, for its fruits but studied here in wild populations, stem extension occurred in the autumn at the beginning of the dry season, flowering and fruiting occurred in the spring at the end of the dry season, and new roots grew in the summer during the wet season. The asynchrony of vegetative and reproductive growth reduces competitive sink effects, which may be advantageous for wild populations growing in infertile rocky soils. Seasonal patterns of sugars in the roots and especially the stems of S. queretaroensis were closely related to the main phenological stages, becoming lower in concentration during periods of major stem extension. Cessation of stem extension occurred in 100-year-old plants for which injection of GA3 reinitiated such growth. Isolated chlorenchyma cylinders had maximum extension in a bathing solution containing 0.1 ?M gibberellic acid.",,,,,,,,,"http://hdl.handle.net/20.500.12104/41808","http://www.scopus.com/inward/record.url?eid=2-s2.0-0031937281&partnerID=40&md5=67f060fbbcd78146a2aebedad0965515",,,,,,"1",,"Tree Physiology",,"59

64",,"18",,"Scopus

WOS",,,,,,"Phenology; Photosynthetic photon flux; Pitayos; Soluble sugars; Stem extension",,,,,,"Growth and development of the arborescent cactus Stenocereus queretaroensis in a subtropical semiarid environment, including effects of gibberellic acid",,"Article" "43560","123456789/35008",,"Ortuño-Sahagún, D., Laboratorio de Desarrollo y Regeneración Neural, Instituto de Neurobiología, Universidad de Guadalajara Camino Ing. R. Padilla Sánchez, 2100, Las Agujas, Zapopan 44600 Jalisco, Mexico; González, R.M., Laboratory of Cellular and Molecular Neurobiology, Division of Neuroscience, IMSS, Guadalajara Jalisco, Mexico; Verdaguer, E., Department of Cellular Biology, Faculty of Biology, Nucli Universitari de Pedralbes, 08028 Barcelona, Spain; Huerta, V.C., Laboratory of Cellular and Molecular Neurobiology, Division of Neuroscience, IMSS, Guadalajara Jalisco, Mexico; Torres-Mendoza, B.M., Centro de Investigación Biomédica de Occidente, IMSS, Universidad de Guadalajara, Guadalajara Jalisco, Mexico; Lemus, L., Depto. de Neonatología, Hosp. de Pediatría, IMSS, Guadalajara Jalisco, Mexico; Rivera-Cervantes, M.C., Dept. of Cell and Molec. Biology, Neurobiol. Inst., University of Guadalajara, Guadalajara Jalisco, Mexico; Camins, A., Unitat de Farmacologia i Farmacognòsia Facultat de Farmàcia, Institut de Biomedicina (IBUB), Nucli Universitari de Pedralbes, 08028 Barcelona, Spain; Zárate, C.B., Laboratorio de Desarrollo y Regeneración Neural, Instituto de Neurobiología, Universidad de Guadalajara Camino Ing. R. Padilla Sánchez, 2100, Las Agujas, Zapopan 44600 Jalisco, Mexico, Laboratory of Cellular and Molecular Neurobiology, Division of Neuroscience, IMSS, Guadalajara Jalisco, Mexico, Department of Cell and Molecular Biology, CUCBA, University of Guadalajara, Km. 15.5 Carr. Nogales, Zapopan Jalisco, Mexico",,"Ortuno-Sahagun, D.

Gonzalez, R.M.

Verdaguer, E.

Huerta, V.C.

Torres-Mendoza, B.M.

Lemus, L.

Rivera-Cervantes, M.C.

Camins, A.

Zarate, C.B.",,"2014",,"Current knowledge concerning the molecular mechanisms of the cellular response to excitotoxic insults in neurodegenerative diseases is insufficient. Although glutamate (Glu) has been widely studied as the main excitatory neurotransmitter and principal excitotoxic agent, the neuroprotective response enacted by neurons is not yet completely understood. Some of the molecular participants have been revealed, but the signaling pathways involved in this protective response are just beginning to be identified. Here, we demonstrate in vivo that, in response to the cell damage and death induced by Glu excitotoxicity, neurons orchestrate a survival response through the extracellular signal-regulated kinase (ERK) signaling pathway by increasing ERK expression in the rat hippocampal (CA1) region, allowing increased neuronal survival. In addition, this protective response is specifically reversed by U0126, an ERK inhibitor, which promotes cell death only when it is administered together with Glu. Our findings demonstrate that the ERK signaling pathway has a neuroprotective role in the response to Glu-induced excitotoxicity in hippocampal neurons. Therefore, the ERK signaling pathway may be activated as a cellular response to excitotoxic injury to prevent damage and neural loss, representing a novel therapeutic target in the treatment of neurodegenerative diseases. " 2013 Springer Science+Business Media New York.