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Titolo:
Effects of neuropathic and non-neuropathic isomers of tricresyl phosphate and their microsomal activation on the production of axon-like processes bydifferentiating mouse N2a neuroblastoma cells
Autore:
Fowler, MJ; Flaskos, J; McLean, WG; Hargreaves, AJ;
Indirizzi:
Nottingham Trent Univ, Dept Life Sci, Nottingham NG11 8NS, England Nottingham Trent Univ Nottingham England NG11 8NS gham NG11 8NS, England Aristotelian Univ Salonika, Fac Med Vet, Lab Biochem & Toxicol, GR-54006 Salonika, Greece Aristotelian Univ Salonika Salonika Greece GR-54006 006 Salonika, Greece Univ Liverpool, Dept Pharmacol & Therapeut, Liverpool L69 3BX, Merseyside,England Univ Liverpool Liverpool Merseyside England L69 3BX X, Merseyside,England
Titolo Testata:
JOURNAL OF NEUROCHEMISTRY
fascicolo: 3, volume: 76, anno: 2001,
pagine: 671 - 678
SICI:
0022-3042(200102)76:3<671:EONANI>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
ORTHO-CRESYL PHOSPHATE; INDUCED DELAYED NEUROTOXICITY; ORGANOPHOSPHORUS ESTERS; NEURITE OUTGROWTH; PC12 CELLS; IN-VITRO; PROTEINS; NEUROFILAMENTS; OPIDN; DEGRADATION;
Keywords:
axon outgrowth; neurofilament heavy chain; tricresyl phosphate and metabolic activation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Hargreaves, AJ Nottingham Trent Univ, Dept Life Sci, Clifton Lane, Nottingham NG11 8NS, England Nottingham Trent Univ Clifton Lane Nottingham England NG11 8NS
Citazione:
M.J. Fowler et al., "Effects of neuropathic and non-neuropathic isomers of tricresyl phosphate and their microsomal activation on the production of axon-like processes bydifferentiating mouse N2a neuroblastoma cells", J NEUROCHEM, 76(3), 2001, pp. 671-678

Abstract

The aim of this work was to investigate the sublethal neuropathic effects of tricresyl phosphate (TCP: mixed isomers), triorthocresyl phosphate (TOCP) and triparacresyl phosphate (TPCP) on differentiating mouse N2a neuroblastoma cells. This was achieved by a combination of measurements of cell viability, axon outgrowth and the levels of cytoskeletal proteins detectable onwestern blots of extracts from cells induced to differentiate in the presence and absence of the compounds. In a time-course experiment TCP inhibitedthe outgrowth of axon-like processes following exposure times of 24 h or longer. Dose-response experiments indicated that TCP and TOCP exhibited similar sustained levels of toxicity following both 24 and 48h exposure, with no significant difference between their respective IC50 values. By contrast,TPCP demonstrated a transient effect on the outgrowth of axon-like processes, which was detectable after 24 but not 48 h of exposure. Isomer-specificpatterns of toxicity were also evident at earlier time-points, with only the ortho isomer showing significant levels of inhibition of axon outgrowth following 4-8h exposure. Probing of western blots with antibodies against cytoskeletal proteins indicated that the inhibition of axon outgrowth by these compounds was associated with a sustained reduction in the levels of phosphorylated neurofilament heavy chain. The inhibitory effect on axon outgrowth of TOCP but not TPCP was enhanced in the presence of a microsomal activation system. Since TOCP is the most neuropathic of the isomers of TCP in vivo, differentiating N2a cells provide a useful cellular system for mechanistic studies of the neurodegenerative effects of this organophosphate.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/09/20 alle ore 10:40:57