Treptow-van Lishaut S, Rechkemmer G, Rowland I, Dolara P, Pool-Zobel B L
Institute of Nutritional Physiology, Federal Research Centre for Nutrition, Karlsruhe, Germany.
Eur J Nutr. 1999 Apr;38(2):76-83. doi: 10.1007/s003940050047.
Glutathione S-transferases (GSTs)* are an important class of phase II, predominantly detoxifying, enzymes. The supergene family is composed of several isoenzymes, hetero- and homodimers, with tissue specific distribution and levels of expression. The hypothesis is that a higher expression of individual proteins within a specific tissue may be associated with a decreased burden of exposure to reactive carcinogens and ultimately with a decreased cancer risk in this tissue.
Since nutrition is expected to contribute to the gene expression, it was the aim of this study to investigate the impact of dietary factors, especially resistant starch, and of the gut microflora, which may be influenced by diet, on the GSTs in colon cells of rats.
For this, a technique using high pressure liquid chromatography was established with which for the first time GST isoenzymes were analysed in colon cells and compared to the levels of the corresponding proteins in the liver of the same rat.
It was found that colon cells contain mainly GST pi and low amounts of mu but not GST alpha. In contrast, the predominant form of GSTs in the liver was alpha, then mu and hardly and pi Altogether, liver cells had approximately tenfold more total GSTs than colon cells. The feeding of "Crystalean", a retrograded, high amylose starch which alters the fermentation profile and the composition of the microflora, led to higher levels of GST pi in the colon. Furthermore, the comparison of GSTs in colon cells of germ-free rats revealed they were much lower than those observed in rats with conventional microflora.
These findings clearly demonstrate that the gut bacteria, or their metabolic products, enhance GST expression. The studies support the hypothesis that nutrition--by affecting the gut flora--may induce this potentially protective and important class of phase II enzymes in important tumor target cells.
谷胱甘肽S-转移酶(GSTs)*是一类重要的II期酶,主要起解毒作用。这个超基因家族由几种同工酶、异源二聚体和同源二聚体组成,具有组织特异性分布和表达水平。假说是特定组织内单个蛋白质的高表达可能与活性致癌物暴露负担的降低相关,最终与该组织中癌症风险的降低相关。
由于营养有望影响基因表达,本研究的目的是调查饮食因素,尤其是抗性淀粉,以及可能受饮食影响的肠道微生物群对大鼠结肠细胞中GSTs的影响。
为此,建立了一种使用高压液相色谱的技术,首次对结肠细胞中的GST同工酶进行分析,并与同一只大鼠肝脏中相应蛋白质的水平进行比较。
发现结肠细胞主要含有GST π,含有少量的GST μ,但不含GST α。相比之下,肝脏中GSTs的主要形式是α,然后是μ,几乎没有π。总体而言,肝细胞中的总GSTs比结肠细胞多大约十倍。喂食“Crystalean”(一种回生的高直链淀粉,可改变发酵谱和微生物群组成)会导致结肠中GST π水平升高。此外,对无菌大鼠结肠细胞中GSTs的比较显示,其水平远低于具有传统微生物群的大鼠。
这些发现清楚地表明,肠道细菌或其代谢产物可增强GST表达。这些研究支持以下假说:营养通过影响肠道菌群,可能在重要的肿瘤靶细胞中诱导这类具有潜在保护作用的重要II期酶。