Release of endogenous hydrogen sulfide in enteric nerve cells suppresses intestinal motility during severe acute pancreatitis

• 来源期刊: 生物化学与生物物理学报（英文版）
• 关键词: hydrogen sulfide enteric nerve cells intestinal motility inflammation severe acute pancreatitis
• 年，卷（期）: 2020,（1）
• 页码范围: 64-71
• 页数: 8页
• 语种: 英文
• DOI: 10.1093/abbs/gmz139

摘要

Previous studies have shown that during severe acute pancreatitis (SAP) attacks,hydrogen sulfide (H2S) is released in the colon.However,the roles played by H2S in regulating enteric nerves remain unclear.In this study,we examined the association between SAP-induced H2S release and loss of intestinal motility,and also explored the relevant mechanism in enteric nerve cells.A rat SAP model was constructed and enteric nerve cells were prepared.Intestinal mobility was evaluated by measuring the number of bowel movements at indicated time points and by performing intestinal propulsion tests.The production of inflammatory cytokines during a SAP attack was quantified by ELISA,and the levels of cystathionine-y-lyase (CSE) and cystathionine-β-synthase (CBS) were examined by immunohistochemistry and western blot analysis.In vivo studies showed that PI3K/Akt/Sp1 signaling in enteric nerve cells was blocked,confirming the mechanism of endogenous H2S formation by western blot analysis and immunofluorescence.Our results also showed that rats with SAP symptoms had reduced intestinal motility.Furthermore,PI3K/Akt/Sp1 signaling was triggered and CSE expression was up-regulated,and these changes were associated with H2S formation in the colon.In addition,propargylglycine reduced the levels of inflammatory cytokines and suppressed the release of H2S.Enteric nerve cells that were incubated with LY294002 and transfected with a Sp1-knockdown vector displayed decreased levels of CSE production,which led to a decrease in H2S production.These results suggest that SAP symptoms suppressed the intestinal motility of rats via the release of H2S in enteric nerve cells,which was dependent on the inflammation-induced PI3K/Akt/Sp1 signaling pathway.