研究発表を行った学会；第７７回日本生化学会大会
２００４年１０月１３日〜１０月１６日（横浜）
タイトル；THE ER STRESS PATHWAY INVOLVING CHOP, IS ACTIVATED IN THE LUNG OF SEPTIC SHOCK MODEL MOUSE
発表者；遠藤　元誉　氏
　　　（熊本大学　大学院医学薬学研究部　分子遺伝分野　and　呼吸器病態学分野）
Abstract；
CHOP is a C/EBP family transcription factor, which is involved in endoplasmic reticulum (ER) stress-mediated apoptosis. We previously reported that nitric oxide (NO) -induced apoptosis is mediated by the ER stress pathway involving ATF6 activation and CHOP induction (1). In septic shock lung, inducible form NO synthase (iNOS) is induced and a large amount of NO is produced. Therefore, we asked whether the ER stress pathway is activated and is involved in the pathogenesis of the septic shock lung.
Wild and chop knockout mice were injected with bacterial lipopolysaccharide (LPS) intraperitoneally. In wild mice, iNOS mRNA was induced in the lung at 2 h after LPS treatment. Under these conditions, mRNAs for ATF4 and Xbp-1, transcriptional activators of the chop gene, were also induced at 2 h. CHOP mRNA was induced a little later and reached a maximum at 6 h. In chop knockout mice, these mRNAs except CHOP were induced as in wild mice. In wild mice, CHOP-positive cells including type II epithelial cells were detected at 12 h by immunohistochemical analysis. We also detected apoptotic cells in the LPS-treated mouse lung at 12h by TUNEL staining. Apoptotic cells detected in the chop knockout mouse lung decreased compared with wild mouse. Besides, we showed that transfection of CHOP induce apoptosis in the human lung-derived A549 cells. These results show that the ER stress pathway involving CHOP is activated and the induced CHOP plays a key role in the pathogenesis of septic shock lung.
(1) Gotoh, T., et al. (2002), JBC 277, 12343-12350.