| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
E-mail contact: hgaskins{at}uiuc.edu
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.
Key words: IEC-18 • colorectal cancer • ulcerative colitis • epithelial hyperproliferation • microarray analysis
This article has been cited by other articles:
|
|
 |
|
  H. Zhang, S. M. Moochhala, and M. Bhatia Endogenous Hydrogen Sulfide Regulates Inflammatory Response by Activating the ERK Pathway in Polymicrobial Sepsis J. Immunol., September 15, 2008; 181(6): 4320 - 4331. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-X. Shi, Y. Chen, Y.-Z. Zhu, G.-Y. Huang, P. K. Moore, S.-H. Huang, T. Yao, and Y.-C. Zhu Chronic sodium hydrosulfide treatment decreases medial thickening of intramyocardial coronary arterioles, interstitial fibrosis, and ROS production in spontaneously hypertensive rats Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2093 - H2100. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-J. Cai, M.-J. Wang, P. K. Moore, H.-M. Jin, T. Yao, and Y.-C. Zhu The novel proangiogenic effect of hydrogen sulfide is dependent on Akt phosphorylation Cardiovasc Res, October 1, 2007; 76(1): 29 - 40. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Yang, W. Yang, L. Wu, and R. Wang H2S, Endoplasmic Reticulum Stress, and Apoptosis of Insulin-secreting Beta Cells J. Biol. Chem., June 1, 2007; 282(22): 16567 - 16576. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Zhi, A. D. Ang, H. Zhang, P. K. Moore, and M. Bhatia Hydrogen sulfide induces the synthesis of proinflammatory cytokines in human monocyte cell line U937 via the ERK-NF-{kappa}B pathway J. Leukoc. Biol., May 1, 2007; 81(5): 1322 - 1332. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Attene-Ramos, E. D. Wagner, H. R. Gaskins, and M. J. Plewa Hydrogen Sulfide Induces Direct Radical-Associated DNA Damage Mol. Cancer Res., May 1, 2007; 5(5): 455 - 459. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Baskar, L. Li, and P. K. Moore Hydrogen sulfide-induces DNA damage and changes in apoptotic gene expression in human lung fibroblast cells FASEB J, January 1, 2007; 21(1): 247 - 255. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Cao, S. Adhikari, A. D. Ang, P. K. Moore, and M. Bhatia Mechanism of induction of pancreatic acinar cell apoptosis by hydrogen sulfide Am J Physiol Cell Physiol, September 1, 2006; 291(3): C503 - C510. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ramasamy, S. Singh, P. Taniere, M. J. S. Langman, and M. C. Eggo Sulfide-detoxifying enzymes in the human colon are decreased in cancer and upregulated in differentiation Am J Physiol Gastrointest Liver Physiol, August 1, 2006; 291(2): G288 - G296. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Ridlon, D.-J. Kang, and P. B. Hylemon Bile salt biotransformations by human intestinal bacteria J. Lipid Res., February 1, 2006; 47(2): 241 - 259. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Attene-Ramos, E. D. Wagner, M. J. Plewa, and H. R. Gaskins Evidence That Hydrogen Sulfide Is a Genotoxic Agent Mol. Cancer Res., January 1, 2006; 4(1): 9 - 14. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Yang, K. Cao, L. Wu, and R. Wang Cystathionine {gamma}-Lyase Overexpression Inhibits Cell Proliferation via a H2S-dependent Modulation of ERK1/2 Phosphorylation and p21Cip/WAK-1 J. Biol. Chem., November 19, 2004; 279(47): 49199 - 49205. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Huycke and H. R. Gaskins Commensal Bacteria, Redox Stress, and Colorectal Cancer: Mechanisms and Models Exp Biol Med, July 1, 2004; 229(7): 586 - 597. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
