Inhalation of low-level formaldehyde increases the Bcl-2/Bax expression ratio in the hippocampus of immunologically sensitized mice.
OBJECTIVE
A recent study from our research group showed that repeated exposure to low-level formaldehyde (FA) increases the production of nerve growth factor, involving the survival and maintenance of neurons, in the hippocampus of immunized mice. In the present study, we examined the effects of FA on apoptotic mechanisms regulating survival and death of cells and on N-methyl-D-aspartate (NMDA) receptors related to hippocampal functions in the mouse hippocampus.


METHODS
Western blot analyses were performed for Bcl-2, Bax and NMDA receptor subtypes 2A and 2B of the hippocampus taken from C3H mice exposed to 0 or 400 ppb of FA with or without ovalbumin (OVA) immunization. Immunohistochemical analysis for active caspase-3 was also carried out for these mice.


RESULTS
The ratio of Bcl-2 to Bax expression levels significantly increased with 400-ppb FA exposure in OVA-immunized mice but not in mice without OVA immunization, although differences in each protein level were not significant among groups. Active caspase- 3-immunoreactive cells were found in the hippocampus. However, the number was only a few and not significantly affected by FA exposure and OVA immunization. NMDA receptor type 2A and 2B expression levels of FA-exposed mice were sustained at comparative levels with those for the control mice with or without OVA immunization.


CONCLUSIONS
These results indicate that changes in the Bcl-2/Bax expression ratio, which occurs with low-level FA exposure and immunization and may follow enhancement of nerve growth factor production, exerts a protective effect against cell death by apoptosis.
Tsukahara
Shinji
S
National Institute for Environmental Studies, Tsukuba, Japan.
Yamamoto
Shoji
S
Tin-Tin-Win-Shwe
Ahmed
Sohel
S
Kunugita
Naoki
N
Arashidani
Keiichi
K
Fujimaki
Hidekazu
H
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects / Q000378:metabolism*; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D019610:Cytoprotection / Q000187:drug effects / Q000276:immunology*; D005260:Female; D005557:Formaldehyde / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D007114:Immunization; D051379:Mice; D008809:Mice, Inbred C3H; D009410:Nerve Degeneration / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000633:toxicity; D010047:Ovalbumin / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D053148:Caspase 3; D005557:Formaldehyde; D020932:Nerve Growth Factor; D009498:Neurotoxins; D010047:Ovalbumin; D019253:Proto-Oncogene Proteins c-bcl-2; D016194:Receptors, N-Methyl-D-Aspartate; D051028:bcl-2-Associated X Protein; C121001:NR2B NMDA receptor; C505409:Casp3 protein, mouse