| RRC ID |
54856
|
| 著者 |
Kurata K, Kawahara H, Nishimura K, Jisaka M, Yokota K, Shimizu H.
|
| タイトル |
Skatole regulates intestinal epithelial cellular functions through activating aryl hydrocarbon receptors and p38.
|
| ジャーナル |
Biochem Biophys Res Commun
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| Abstract |
Intestinal bacteria produce skatole (3-methylindole) from tryptophan in dietary proteins and ingesting large quantities of animal protein is associated with increased fecal skatole concentrations. Although possibly associated with disrupted intestinal homeostasis, the influence of skatole on intestinal epithelial cellular function has not been characterized in detail. The present study aimed to determine whether skatole induces intestinal epithelial cell (IEC) dysfunction. We found that skatole dose-dependently caused IEC death and time-dependently induced IEC apoptosis. Since skatole directly interacts with aryl hydrocarbon receptors (AhR), we investigated whether these receptors influence the skatole-induced death of IEC. In addition to increased AhR transcriptional activity induced by skatole, the AhR antagonist CH223191 partially suppressed of skatole-induced IEC death. Extracellular signal-related kinase (ERK), p38 and c-Jun N-terminal kinase (JNK) are mitogen-activated protein kinases (MAPK) induced by skatole. None of them were repressed by CH223191, whereas the p38 inhibitor SB203580 promoted skatole-induced IEC death. These findings together indicated that skatole induces both AhR-dependent activation pathways and the AhR-independent activation of p38, consequently regulating the amount of IEC death. Accumulating evidence indicates that consuming large amounts of animal protein is associated with the pathogenesis and progression of inflammatory bowel diseases (IBD). Thus, intestinal skatole production induced by large amounts of dietary animal protein might be associated via IEC death with intestinal pathologies such as IBD.
|
| 巻・号 |
510(4)
|
| ページ |
649-655
|
| 公開日 |
2019-3-19
|
| DOI |
10.1016/j.bbrc.2019.01.122
|
| PII |
S0006-291X(19)30151-2
|
| PMID |
30739789
|
| MeSH |
Apoptosis
Basic Helix-Loop-Helix Transcription Factors / metabolism*
Caco-2 Cells
Cell Death
Enzyme Activation
Humans
Intestinal Mucosa / cytology*
Intestinal Mucosa / metabolism
Intestines / microbiology*
Receptors, Aryl Hydrocarbon / metabolism*
Skatole / metabolism*
p38 Mitogen-Activated Protein Kinases / metabolism*
|
| IF |
2.705
|
| 引用数 |
1
|
| リソース情報 |
| ヒト・動物細胞 |
CACO-2(RCB0988) |
