Altered expression of DJ-1 in the hippocampal cells following in vivo and in vitro neuronal damage induced by trimethyltin.
Trimethyltin chloride (TMT) is known to produce neuronal damage in the dentate gyrus at least in part via oxidative stress. DJ-1, an oncogene product, is known to act as an anti-oxidant to prevent neuronal damage in dopaminergic neurons. The aim of this study was to determine the alterations in DJ-1 expression in the hippocampal cells of mice after in vivo and in vitro treatment with TMT. In naïve animals, DJ-1 was ubiquitously expressed in the hippocampus, in which the CA1 pyramidal cell layer and dentate granule cell layer had lower and higher levels of it, respectively. An intraperitoneal injection of TMT at the dose of 2.8 mg/kg produced DJ-1 up-regulation in the CA1 pyramidal cell layer, CA3 stratum lucidum, dentate molecular layer, and dentate hilus, but not in the dentate granule cell layer, on day 3-5 post-treatment. Temporary depletion of endogenous glutathione by the prior subcutaneous injection of 2-cyclohexen-1-one was effective in facilitating neuronal damage and DJ-1 up-regulation in the dentate gyrus induced by an intraperitoneal injection of TMT at the dose of 2.0 mg/kg. In primary cultures of mouse hippocampal cells, DJ-1 was present in neurons, but not in astrocytes. TMT treatment produced a dramatic expression of DJ-1 in the astrocytes in the cultures. Taken together, our data suggest that the DJ-1 protein is positively regulated in response to oxidative stress induced by TMT.
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan.
Reiko
R
Nagashima
Chie
C
Sugiyama
Yuka
Y
Gotoh
Masanori
M
Yoneyama
Nobuyuki
N
Kuramoto
Takahiro
T
Taira
Hiroyoshi
H
Ariga
Kiyokazu
K
Ogita
D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D003512:Cyclohexanones / Q000494:pharmacology; D004347:Drug Interactions; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation / Q000187:drug effects*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology* / Q000293:injuries; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D054464:Peroxiredoxins; D000071617:Protein Deglycase DJ-1; D013997:Time Factors; D014298:Trimethyltin Compounds / Q000633:toxicity*
D003512:Cyclohexanones; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D015513:Oncogene Proteins; D014298:Trimethyltin Compounds; C028215:2-cyclohexen-1-one; C040533:trimethyltin chloride; D054464:Peroxiredoxins; C503466:PARK7 protein, mouse; D000071617:Protein Deglycase DJ-1