VX-induced cell death involves activation of caspase-3 in cultured rat cortical neurons.

Full Abstract

Exposure of cell cultures to organophosphorous compounds such as VX can result in cell death. However, it is not clear whether VX-induced cell death is necrotic or involves programmed cell death mechanisms. Activation of caspases, a family of cysteine proteases, is often involved in cell death, and in particular, caspase-3 activation appears to be a key event in programmed cell death processes including apoptosis. In this study, we investigated VX-induced neuronal cell death, as well as the underlying mechanism in terms of its effect on caspase-3 activity. Primary cortical neuronal cultures were prepared from gestational days 17 to 19 Sprague Dawley rat fetuses. At maturation, the cells were treated with varying concentrations of VX and cell death was evaluated by lactate dehydrogenase (LDH) release. VX induced an increase in LDH release in a concentration-dependent manner. Morphological VX-induced cell death was also characterized by using nuclear staining with propidium iodide and Hoechst 33342. VX induced a concentration- and time-dependent increase in caspase-3 activation. Caspase-3 activation was also confirmed by the proteolytic cleavage of poly(ADP-ribose)polymerase (PARP), an endogenous caspase-3 substrate. These data suggested that in rat cortical neurons, VX-induced cell death via a programmed cell death pathway that involves changes in caspase-3 protease.

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Author information

Author/s: Tenn, Catherine C (CC); Wang, Yushan (Y);

Affiliation: Medical Therapy Group, DRDC Suffield, P.O. Box 4000, Station Main, Medicine Hat, Alberta T1A 8K6, Canada. catherine.tenn(-atsign-)ddrdc-rddc.gc.ca

Journal and publication information

Publication Type: Journal Article

Journal: Neuroscience letters (Neurosci Lett), published in Ireland. (Language: eng)

Reference: 2007-May; vol 417 (issue 2) : pp 155-9

Dates: Created 2007/04/16; Completed 2007/07/25;

PMID: 17367932, status: MEDLINE (last retrieval date: 12/26/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Apoptosis - drug effects; physiology
Caspase 3 - drug effects; metabolism
Cells, Cultured
Cerebral Cortex - drug effects; enzymology; physiopathology
Cholinesterase Inhibitors - toxicity
Dose-Response Relationship, Drug
Enzyme Activation - drug effects; physiology

Indicators and Reagents
L-Lactate Dehydrogenase - metabolism
Neurons - drug effects; enzymology
Organothiophosphorus Compounds - toxicity
Poly(ADP-ribose) Polymerases - metabolism
Rats
Rats, Sprague-Dawley
Time Factors

Associated Chemicals: Cholinesterase Inhibitors (0) ; Indicators and Reagents (0) ; Organothiophosphorus Compounds (0) ; VX (50782-69-9) ; L-Lactate Dehydrogenase (EC 1.1.1.27) ; Adprt protein, rat (EC 2.4.2.30) ; Poly(ADP-ribose) Polymerases (EC 2.4.2.30) ; Caspase 3 (EC 3.4.22.-)

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