Detrimental effects for colonocytes of an increased exposure to luminal hydrogen sulfide: The adaptive response
Detrimental effects for colonocytes of an increased exposure to luminal hydrogen sulfide: The adaptive response
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DOI：
10.1016/j.freeradbiomed.2016.01.028
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发表时间：
2016-04-01
影响因子：
7.4
通讯作者：
Blachier, Francois
中科院分区：
文献类型：
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作者：
Beaumont, Martin;Andriamihaja, Mireille;Blachier, Francois
肠道微生物群的蛋白质发酵在大肠腔中释放各种氨基酸衍生的代谢物。其中，过量的硫化氢（H2S）被怀疑对结肠上皮细胞能量代谢和DNA完整性有害。本研究的第一个目的是评估大鼠上皮细胞对H2S暴露增加的反应。来自结肠细胞孵育和结肠内滴注的实验表明，低毫摩尔浓度的硫化物供体NaHS可逆地抑制结肠细胞线粒体耗氧量，并增加缺氧诱导因子1 α（Hif-1 α）以及炎症相关基因即诱导型一氧化氮合酶（iNos）和白细胞介素-6（IL-6）的基因表达。此外，大鼠结肠细胞H2S解毒能力严重受损的一氧化氮的存在下。基于γ H（2）AX ICW技术，NaHS不诱导结肠细胞DNA损伤。由于H2S是由肠道微生物群从含硫氨基酸中产生的，因此本研究的第二个目的是研究高蛋白饮食（HPD）对大肠腔硫化物含量和结肠细胞中参与H2S解毒的基因表达的影响。我们发现，HPD显着增加大肠中的H2S含量，但伴随的内容物质量的增加维持了管腔硫化物浓度。HPD还引起结肠细胞中硫化物醌还原酶（Sqr）基因表达的增加，表明对H2S细菌产量增加的适应性反应。总之，低毫摩尔NaHS浓度严重影响结肠细胞呼吸，与肠道炎症相关基因表达增加有关。虽然HPD增加了大肠的硫化物含量，但结肠对这种修饰的适应性反应限制了上皮暴露于这种有害的细菌代谢物。(C)2016 Elsevier Inc. All rights reserved.
Protein fermentation by the gut microbiota releases in the large intestine lumen various amino-acid derived metabolites. Among them, hydrogen sulfide (H2S) in excess has been suspected to be detrimental for colonic epithelium energy metabolism and DNA integrity. The first objective of this study was to evaluate in rats the epithelial response to an increased exposure to H2S. Experiments from colonocyte incubation and intra-colonic instillation indicate that low millimolar concentrations of the sulfide donor NaHS reversibly inhibited colonocyte mitochondrial oxygen consumption and increased gene expression of hypoxia inducible factor 1 alpha (Hif-1 alpha) together with inflammation-related genes namely inducible nitric oxide synthase (iNos) and interleukin-6 (Il-6). Additionally, rat colonocyte H2S detoxification capacity was severely impaired in the presence of nitric oxide. Based on the gamma H(2)AX ICW technique, NaHS did not induce DNA damage in colonocytes. Since H2S is notably produced by the gut microbiota from sulfur containing amino acids, the second objective of the study was to investigate the effects of a high protein diet (HPD) on large intestine luminal sulfide content and on the expression of genes involved in H2S detoxification in colonocytes. We found that HPD markedly increased H2S content in the large intestine but the concomitant increase of the content mass maintained the luminal sulfide concentration. HPD also provoked an increase of sulfide quinone reductase (Sqr) gene expression in colonocytes, indicating an adaptive response to increased H2S bacterial production. In conclusion, low millimolar NaHS concentration severely affects colonocyte respiration in association with increased expression of genes associated with intestinal inflammation. Although HPD increases the sulfide content of the large intestine, the colonic adaptive responses to this modification limit the epithelial exposure to this deleterious bacterial metabolite. (C) 2016 Elsevier Inc. All rights reserved.