Acute exposure of toluene transiently potentiates p42/44 mitogen-activated protein kinase (MAPK) activity in cultured rat cortical astrocytes.
It has been shown that the inhalation of toluene in rats can cause neuronal apoptosis in the central nervous system. However, the cellular and molecular effects of toluene directly on astrocytes are relatively unknown. We used primary cultures of astrocytes isolated from the neonatal rat cortex as a model to study the toluene effects on cell outcome and associated signal transduction pathways using immunostaining and Western blotting. We observed that acute toluene exposure significantly induced caspase-dependent cell apoptosis and transiently stimulated the activation of p42/44 mitogen-activated protein kinase (MAPK) in the primary astrocytes. Interestingly, the inhibition of the p42/44 MAPK signaling cascade by PD98059 in conjunction with the toluene treatment evoked more cellular apoptosis than toluene alone, suggesting that the toluene-induced transient MAPK activation may play a role in promoting cell survival during the toluene exposure.
Lin
H J
HJ
Center for Bio/Molecular Science and Engineering, Naval Research Laboratory, Code 6910, 4555 Overlook Avenue SW, Washington, DC, USA. jlin@ccs.nrl.navy.mil
Shaffer
K M
KM
Chang
Y H
YH
Barker
J L
JL
Pancrazio
J J
JJ
Stenger
D A
DA
Ma
W
W
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology*; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005419:Flavonoids / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D012997:Solvents; D013268:Stimulation, Chemical; D014050:Toluene / Q000494:pharmacology*
D005419:Flavonoids; D005904:Glial Fibrillary Acidic Protein; D012997:Solvents; D014050:Toluene; D019950:Mitogen-Activated Protein Kinase 1; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one