Methylglyoxal causes strong weakening of detoxifying capacity and apoptotic cell death in rat hippocampal neurons. (Articolo in rivista)

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  • Methylglyoxal causes strong weakening of detoxifying capacity and apoptotic cell death in rat hippocampal neurons. (Articolo in rivista) (literal)
Anno
  • 2008-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1016/j.biocel.2007.07.019 (literal)
Alternative label
  • S. Di Loreto a; V. Zimmitti b; P. Sebastiani a; C. Cervelli c; S. Falone d; F. Amicarelli b (2008)
    Methylglyoxal causes strong weakening of detoxifying capacity and apoptotic cell death in rat hippocampal neurons.
    in International journal of biochemistry & cell biology; Pergamon-Elsevier Science Ltd., Oxford (Regno Unito)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • S. Di Loreto a; V. Zimmitti b; P. Sebastiani a; C. Cervelli c; S. Falone d; F. Amicarelli b (literal)
Pagina inizio
  • 245 (literal)
Pagina fine
  • 257 (literal)
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  • 40 (literal)
Rivista
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  • 12 (literal)
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  • 2 (literal)
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  • Scopu (literal)
  • Google Scholar (literal)
  • ISI Web of Science (WOS) (literal)
  • PubMe (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • a CNR, ITIO, I-67100 Laquila, Italy b Univ Aquila, Dept Basic & Appl Biol, I-67100 Laquila, Italy c Reg Ctr Immunohaematol & Tissue Typing ASL 4, Laquila, Italy d Fac Med G Annunzio, Excellent Ctr Aging Studies, Dept Biomed Sci, I-66013 Chieti, Italy (literal)
Titolo
  • Methylglyoxal causes strong weakening of detoxifying capacity and apoptotic cell death in rat hippocampal neurons. (literal)
Abstract
  • The hippocampus is known to play a crucial role in learning and memory. Recent data from literature showthat cognitive problems, common to aged or diabetic patients, may be related to accumulation of toxic ?-oxoaldehydes such as methylglyoxal. Thus, it is possible that methylglyoxal could be, at least in part, responsible for the impairment of cognitive functions, and the knowledge of the mechanisms through which this compound elicits neuronal toxicity could be useful for the development of possible therapeutic strategies. We previously reported a high susceptibility of hippocampal neurons to methylglyoxal, through an oxidation-dependent mechanism. In the present study,we extend our investigation on the molecular mechanisms which underlie methylglyoxal toxicity, focusing on possible effects on expression and activity of glyoxalases, its main detoxifying enzymes, and glutathione peroxidase, as well as on the levels of reduced glutathione. We also investigate methylglyoxal-induced modulation of brain derived neurotrophic factor and proinflammatory cytokines. Our results show that methylglyoxal causes a dramatic depletion of reduced glutathione and a significant inhibition of both glyoxalase and glutathione peroxidase activities. Furthermore, methylglyoxal treatment seems to affect the expression of inflammatory cytokines and survival factors. In conclusion, our findings suggest that methylglyoxal-induced neurotoxicity occurs through the impairment of detoxification pathway and depletion of reduced glutathione. This, in turn, triggers widespread apoptotic cell death, occurring through the convergence of both mitochondrial and Fas-receptor pathways. (literal)
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