期刊
FASEB JOURNAL
卷 17, 期 8, 页码 1310-+出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.02-0883fje
关键词
IEC-18; colorectal cancer; ulcerative colitis; epithelial hyperproliferation; microarray analysis
Hydrogen sulfide (H2S), produced by commensal sulfate-reducing bacteria, is an environmental insult that potentially contributes to chronic intestinal epithelial disorders. We tested the hypothesis that exposure of nontransformed intestinal epithelial cells (IEC-18) to the reducing agent sodium hydrogen sulfide (NaHS) activates molecular pathways that underlie epithelial hyperplasia, a phenotype common to both ulcerative colitis (UC) and colorectal cancer. Exposure of IEC-18 cells to NaHS rapidly increased the NADPH/NADP ratio, reduced the intracellular redox environment, and inhibited mitochondrial respiratory activity. The addition of 0.2-5 mM NaHS for 4 h increased the IEC-18 proliferative cell fraction (P<0.05), as evidenced by analysis of the cell cycle and proliferating cell nuclear antigen expression, while apoptosis occurred only at the highest concentration of NaHS. Thirty minutes of NaHS exposure increased (P<0.05) c-Jun mRNA concentrations, consistent with the observed activation of mitogen activated protein kinases (MAPK). Microarray analysis confirmed an increase (P<0.05) in MAPK-mediated proliferative activity, likely reflecting the reduced redox environment of NaHS-treated cells. These data identify functional pathways by which H2S may initiate epithelial dysregulation and thereby contribute to UC or colorectal cancer. Thus, it becomes crucial to understand how genetic background may affect epithelial responsiveness to this bacterial-derived environmental insult.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据