SO2 inhalation modulates the expression of apoptosis-related genes in rat hippocampus via its derivatives in vivo.
The possible neurotoxicity of SO(2) has been implicated by determining morphological change, oxidative stress, DNA damage and membrane channel alteration in previous studies, however, its detailed mechanisms remain unclear. In the present study, we investigated SO(2) inhalation-induced effects on the transcription and translation of several apoptosis-related genes (p53, bax, bcl-2, c-fos, and c-jun) in rat hippocampus, using real-time RT-PCR analysis and western blotting technique, respectively. The results demonstrate that SO(2) statistically increased p53 expression and the ratio of bax to bcl-2 in a concentration-dependent manner. Also, mRNA and protein levels of c-fos and c-jun significantly elevated in proportion to exposure concentration. Then, we treated primary cultured hippocampal neurons with SO(2) derivatives (bisulfite and sulfite, 3:1 M/M), and examined mRNA levels of above genes. The results show that P53, c-fos, c-jun mRNA expression and the ratio of bax to bcl-2 augmented as functions of SO(2) derivative concentration and exposure time, and confirm that SO(2) affected the transcription and translation process of apoptosis-related genes in central nervous system via its derivatives in vivo. The present data provide further evidence for SO(2)-caused neurological insults, and imply that two major pathways associated with p53 and AP-1 might play important roles in the pathogenesis.
Yun
Yang
Y
College of Environment and Resource, Center of Environmental Science and Engineering, Shanxi University, Taiyuan, Shanxi, People's Republic of China.
Li
Hongyan
H
Li
Guangke
G
Sang
Nan
N
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D019254:Genes, bcl-2 / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology*; D019570:Inhalation Exposure / Q000009:adverse effects*; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013447:Sulfites / Q000008:administration & dosage / Q000633:toxicity; D013458:Sulfur Dioxide / Q000008:administration & dosage* / Q000633:toxicity; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
D019253:Proto-Oncogene Proteins c-bcl-2; D013447:Sulfites; D051028:bcl-2-Associated X Protein; D013458:Sulfur Dioxide; C042345:hydrogen sulfite