Baydoun Zahraa A, Rao Muddanna, Khan Islam
Department of Biochemistry, College of Medicine, Kuwait University, Kuwait City, Kuwait.
Department of Anatomy, College of Medicine, Kuwait University, Kuwait City, Kuwait.
Med Princ Pract. 2025;34(1):39-47. doi: 10.1159/000541791. Epub 2024 Nov 4.
Inflammatory bowel diseases which are characterized by endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) signaling pathway are commonly treated with 5-amino salicylic acid (5-ASA). The objective of this study was to investigate the role of 5-amino salicylic acid in the UPR-signaling pathway in experimental colitis.
Colitis was induced in male Sprague-Dawley rats by intrarectal instillation of trinitrobenzene sulfonic acid. Animals received 5-amino salicylic acid (100 mg/kg body weight) 2 h before the induction of colitis and repeated daily until day 7. The animals were sacrificed on day 7 and tissues were collected for analysis.
The expression of protein kinase R (PKR)-like ER kinase (PERK), a mediator of UPR signaling increased significantly (p < 0.05), while inositol-requiring enzyme type-1 (IRE1) and the CCAAT/enhancer-binding homologous protein (CHOP) remained unaltered in the inflamed colon. The expression of glucose-regulated protein-78, activator of transcription factor-4, and phosphorylated-eukaryotic initiation factor-2α (eIF2αP) increased (p < 0.05) in the inflamed colon. However, the levels of eIF2α protein and mRNA expression remained unchanged. Myeloperoxidase activity, colon weight, and infiltration of inflammatory cells increased significantly (p < 0.05) in the submucosa whereas the body weight decreased. These changes were significantly inhibited by 5-amino salicylate treatment.
These findings suggest that the anti-inflammatory properties of 5-amino salicylic acid are mediated through the inhibition of the PERK signaling pathway.
Inflammatory bowel diseases which are characterized by endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) signaling pathway are commonly treated with 5-amino salicylic acid (5-ASA). The objective of this study was to investigate the role of 5-amino salicylic acid in the UPR-signaling pathway in experimental colitis.
Colitis was induced in male Sprague-Dawley rats by intrarectal instillation of trinitrobenzene sulfonic acid. Animals received 5-amino salicylic acid (100 mg/kg body weight) 2 h before the induction of colitis and repeated daily until day 7. The animals were sacrificed on day 7 and tissues were collected for analysis.
The expression of protein kinase R (PKR)-like ER kinase (PERK), a mediator of UPR signaling increased significantly (p < 0.05), while inositol-requiring enzyme type-1 (IRE1) and the CCAAT/enhancer-binding homologous protein (CHOP) remained unaltered in the inflamed colon. The expression of glucose-regulated protein-78, activator of transcription factor-4, and phosphorylated-eukaryotic initiation factor-2α (eIF2αP) increased (p < 0.05) in the inflamed colon. However, the levels of eIF2α protein and mRNA expression remained unchanged. Myeloperoxidase activity, colon weight, and infiltration of inflammatory cells increased significantly (p < 0.05) in the submucosa whereas the body weight decreased. These changes were significantly inhibited by 5-amino salicylate treatment.
These findings suggest that the anti-inflammatory properties of 5-amino salicylic acid are mediated through the inhibition of the PERK signaling pathway.
以内质网（ER）应激和未折叠蛋白反应（UPR）信号通路激活为特征的炎症性肠病通常用5-氨基水杨酸（5-ASA）治疗。本研究的目的是探讨5-氨基水杨酸在实验性结肠炎的UPR信号通路中的作用。
通过直肠内注入三硝基苯磺酸在雄性Sprague-Dawley大鼠中诱导结肠炎。动物在诱导结肠炎前2小时接受5-氨基水杨酸（100mg/kg体重），并每天重复给药直至第7天。在第7天处死动物并收集组织进行分析。
UPR信号的介质蛋白激酶R（PKR）样内质网激酶（PERK）的表达显著增加（p<0.05），而在炎症结肠中，肌醇需求酶1型（IRE1）和CCAAT/增强子结合同源蛋白（CHOP）保持不变。炎症结肠中葡萄糖调节蛋白78、转录因子4激活剂和磷酸化真核起始因子2α（eIF2αP）的表达增加（p<0.05）。然而，eIF2α蛋白水平和mRNA表达保持不变。黏膜下层髓过氧化物酶活性、结肠重量和炎症细胞浸润显著增加（p<0.05），而体重下降。这些变化被5-氨基水杨酸盐治疗显著抑制。
这些发现表明5-氨基水杨酸的抗炎特性是通过抑制PERK信号通路介导的。
以内质网（ER）应激和未折叠蛋白反应（UPR）信号通路激活为特征的炎症性肠病通常用5-氨基水杨酸（5-ASA）治疗。本研究的目的是探讨5-氨基水杨酸在实验性结肠炎的UPR信号通路中的作用。
通过直肠内注入三硝基苯磺酸在雄性Sprague-Dawley大鼠中诱导结肠炎。动物在诱导结肠炎前2小时接受5-氨基水杨酸（100mg/kg体重），并每天重复给药直至第7天。在第7天处死动物并收集组织进行分析。
UPR信号的介质蛋白激酶R（PKR）样内质网激酶（PERK）的表达显著增加（p<0.05），而在炎症结肠中，肌醇需求酶1型（IRE1）和CCAAT/增强子结合同源蛋白（CHOP）保持不变。炎症结肠中葡萄糖调节蛋白78、转录因子4激活剂和磷酸化真核起始因子2α（eIF2αP）的表达增加（p<0.05）。然而，eIF2α蛋白水平和mRNA表达保持不变。黏膜下层髓过氧化物酶活性、结肠重量和炎症细胞浸润显著增加（p<0.05），而体重下降。这些变化被5-氨基水杨酸盐治疗显著抑制。
这些发现表明5-氨基水杨酸的抗炎特性是通过抑制PERK信号通路介导的。
