1-BP inhibits NF-kappaB activity and Bcl-xL expression in astrocytes in vitro and reduces Bcl-xL expression in the brains of rats in vivo.
1-Bromopropane (1-BP) has been widely used as a substitute for chlorofluorocarbon that destroys the ozone layer. Although the central neurotoxicity of 1-BP has been recently reported, a molecular mechanism is not clear. In particular, the effects on cells in brain have not been fully analyzed. Here, we studied the effects of 1-BP on the activation of transcription factors involved in anti-apoptotic function or cell survival in astrocytes. Astrocytoma cell lines, U251, U373 and VM, or murine primary astrocytes were used for in vitro assay. DNA binding activities of NF-kappaB in these cells induced by interleukin (IL)-1 or LPS were inhibited by 1-BP. Consequently, the treatment of U251 cells with 1-BP resulted in suppression of NF-kappaB reporter activity. Furthermore, 1-BP blocked IkappaBalpha degradation, which is important for NF-kappaB activation. In addition, the level of Bcl-xL mRNA, which is known as an anti-apoptotic gene, were reduced in U251 treated with 1-BP or in the brain from rat exposed to 1-BP (400 ppm, 12 weeks). These results suggest that subchronic inhalation exposure to 1-BP vapor may affect the Bcl-xL expression in astrocytes.
Yoshida
Y
Y
Department of Immunology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Kitakyushu 807-8555, Japan. freude@med.uoeh-u.ac.jp
Liu
J Q
JQ
Nakano
Y
Y
Ueno
S
S
Ohmori
S
S
Fueta
Y
Y
Ishidao
T
T
Kunugita
N
N
Yamashita
U
U
Hori
H
H
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000633:toxicity; D020672:I-kappa B Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012997:Solvents / Q000633:toxicity*; D014162:Transfection; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism*
C494811:BCL2L1 protein, human; C494812:Bcl2l1 protein, mouse; C494813:Bcl2l1 protein, rat; D006842:Hydrocarbons, Brominated; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; C000606206:Nfkbia protein, rat; D012333:RNA, Messenger; D012997:Solvents; D051020:bcl-X Protein; D000072000:NF-KappaB Inhibitor alpha; C118559:1-bromopropane