glutamine treatment attenuates endoplasmic reticulum stress and apoptosis in tnbs-induced colitis谷氨酰胺治疗变弱内质网应激和凋亡tnbs-induced结肠炎.pdfVIP

Glutamine Treatment Attenuates Endoplasmic Reticulum Stress and Apoptosis in TNBS-Induced Colitis 1,2 2 2 3 ´ 1,2 Irene Crespo , Beatriz San-Miguel , Carolina Prause , Norma Marroni , Marıa J. Cuevas , ´ 1,2 ´ ˜ ´ 1,2 Javier Gonzalez-Gallego , Marıa J. Tunon * ´ ´ ´ ´ ´ 1 Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBERehd), Leon, Spain, 2 Institute of Biomedicine (IBIOMED), University of Leon, ´ Leon, Spain, 3 Porto Alegre Clinical Hospital, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil Abstract Endoplasmic reticulum (ER) stress and apoptotic cell death play an important role in the pathogenesis and perpetuation of inflammatory bowel disease (IBD). We aimed to explore the potential of glutamine to reduce ER stress and apoptosis in a rat model of experimental IBD. Colitis was induced in male Wistar rats by intracolonic administration of 30 mg of 2,4,6- trinitrobenzene sulfonic acid (TNBS). Glutamine (25 mg/dL) was given by rectal route daily for 2 d or 7 d. Both oxidative stress (TBARS concentration and oxidised/reduced glutathione ratio) and ER stress markers (CHOP, BiP, calpain-1 and caspase-12 expression) increased significantly within 48 h of TNBS instillation, and glutamine attenuated the extent of the changes. Glutamine also inhibited the significant increases of ATF6, ATF4 and spliced XBP-1 mRNA levels induced by TNBS instillation. TNBS-colitis resulted in a si