Pro-apoptotic action of macrophage inhibitory cytokine 1 and counteraction of activating transcription factor 3 in carrageenan-exposed enterocytes

Autor: Hwi-Gon Kim, Yong Sik Kim, Seong-Hwan Park, Kee Hun Do, Seungjoon Lee, Chang Gyu Oh, Yuseok Moon, Soon Cheol Ahn, Jiyeon Park, Juil Kim, Hye Jin Choi, Young Chul Park
Rok vydání: 2014
Předmět:
Zdroj: Toxicology Letters. 231:1-8
ISSN: 0378-4274
DOI: 10.1016/j.toxlet.2014.08.022
Popis: Carrageenan (CGN), a widely used food additive, has been shown to injure the epithelial barrier in animal models. This type of damage is a clinical feature of inflammatory bowel disease (IBD) in humans. In the present study, the effects of CGN on pro-apoptotic responses associated with macrophage inhibitory cytokine 1 (MIC-1) regulation in human enterocytes were evaluated. CGN up-regulated the expression of MIC-1 that promoted epithelial cell apoptosis. Although MIC-1 induction was dependent on pro-apoptotic p53 protein, the pro-survival protein activating transcription factor 3 (ATF3) was negatively regulated by p53 expression. However, MIC-1 enhanced the expression of the pro-survival protein ATF3 in enterocytes exposed to CGN. Functionally, MIC-1-mediated epithelial cell apoptosis was counteracted by the pro-survival action of ATF3 in response to CGN exposure. These findings demonstrated that the counterbalance between MIC-1 and ATF3 is critical for deciding the fate of enterocytes under the food chemical stress.
Databáze: OpenAIRE