ニシマツ　シンイチロウ   Shinichiro Nishimatsu   西松　伸一郎    所属   川崎医科大学  医学部 一般教養　自然科学    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Paraquat-induced gene expression in rat lung tissues using a differential display reverse transcription-polymerase chain reaction.
掲載誌名	正式名：Archives of toxicology 略　 称：Arch Toxicol ISSNコード：03405761/14320738
巻・号・頁	76(9),pp.530-537
著者・共著者	Tomita Masafumi, Nohno Tsutomu, Okuyama Toshiko, Nishimatsu Shin-ichiro, Adachi Junko
発行年月	2002/09
概要	Increased formation of reactive oxygen species is a cause of paraquat (PQ)-induced injury and also provides a link between the signaling pathways and transcriptional events that regulate the expression of a large number of genes. However, the molecular mechanisms involved in PQ-induced injury remain unclear. To investigate the changes in gene expression at the onset of PQ injury, we used the differential display-polymerase chain reaction (PCR) method. Rats were treated intra-peritoneally with 20 mg/kg PQ, and after 3 h the lungs were immediately excised. Samples of mRNA from normal and treated rats were used to prepare radiolabeled cDNAs, which were electrophoresed. Then the transcription levels were compared. We isolated 26 fragments of cDNA that were potentially affected by PQ, and determined their nucleotide sequences. Six clones of interest were selected and analyzed further. The reverse transcript-PCR based on their sequence information confirmed the differential expression for five clones: four clones were up-regulated and one was down-regulated. We were particularly interested in two genes that had homology with the known gene: TATA box-binding protein-associated factor, RNA polymerase II, B, 150 kDa (TAFIIB), and a candidate gene for lipodystrophy, Lpin2. Both genes were significantly up-regulated within 3 h of PQ intake and the stimulation continued during our 24-h observation period. In addition, up-regulation of Lpin2 was observed in the lungs, but not in the liver and kidneys. In situ hybridization using lung sections showed that the expression of both genes was strongly visualized in Clara cells and in alveolar macrophages. These findings suggest a stimulation of transcription levels and changes in lipid metabolism in Clara cells and in macrophages in the lungs, which result in their playing a crucial role at the onset of PQ-driven pulmonary injury.
DOI	10.1007/s00204-002-0379-x
文献番号	12242611