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Hydrogen sulfide induces serum‐independent cell cycle entry in nontransformed rat intestinal epithelial cells
Author(s) -
Deplancke Bart,
Gaskins H. Rex
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0883fje
Subject(s) - mapk/erk pathway , microbiology and biotechnology , chemistry , cell growth , apoptosis , biology , signal transduction , cancer research , biochemistry
Hydrogen sulfide (H 2 S), 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 H 2 S 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.