Hatayama Hajime, Iwashita Jun, Kuwajima Akiko, Abe Tatsuya
Molecular Biology Laboratory, Faculty of Bioresource Sciences, Akita Prefectural University, Akita 010-0195, Japan.
Biochem Biophys Res Commun. 2007 May 11;356(3):599-603. doi: 10.1016/j.bbrc.2007.03.025. Epub 2007 Mar 12.
The short fatty acid, butyrate, which is produced by intestinal anaerobic bacteria in the colon, has inhibitory activity on histone deacetylases (HDACs). Treatment of the human colon cancer cell line, LS174T, with 1-2 mM sodium butyrate stimulated MUC2 mucin production, as determined by histological PAS staining of carbohydrate chains of mucin, and confirmed at the protein and mRNA levels by immunoblotting with anti-MUC2 antibody and real-time RT-PCR, respectively. Increases in acetylated histone H3 in the LS174T cells treated with butyrate suggest inhibition of HDACs in these cells. Butyrate-stimulated MUC2 production in the LS174T cells was inhibited by the MEK inhibitor, U0126, implicating the involvement of extracellular signal-regulated kinase (ERK) cascades in this process. Proliferation of the LS174T cells was inhibited by butyrate treatment. Although apoptotic nuclear DNA fragmentation could not be detected, cell-cycle arrest at the G0/G1 phase in the butyrate-treated cells was demonstrated by flow cytometry. Thus butyrate, an HDAC inhibitor, inhibits proliferation of LS174T cells but stimulates MUC2 production in individual cells.
短链脂肪酸丁酸由结肠中的肠道厌氧菌产生，对组蛋白脱乙酰酶（HDAC）具有抑制活性。用1-2 mM丁酸钠处理人结肠癌细胞系LS174T，可刺激MUC2粘蛋白的产生，这通过对粘蛋白碳水化合物链进行组织学PAS染色来确定，并分别通过用抗MUC2抗体进行免疫印迹和实时RT-PCR在蛋白质和mRNA水平上得到证实。用丁酸盐处理的LS174T细胞中乙酰化组蛋白H3的增加表明这些细胞中的HDAC受到抑制。丁酸盐刺激的LS174T细胞中MUC2的产生受到MEK抑制剂U0126的抑制，这表明细胞外信号调节激酶（ERK）级联反应参与了这一过程。丁酸盐处理可抑制LS174T细胞的增殖。虽然未检测到凋亡性核DNA片段化，但通过流式细胞术证明丁酸盐处理的细胞在G0/G1期出现细胞周期停滞。因此，HDAC抑制剂丁酸盐可抑制LS174T细胞的增殖，但可刺激单个细胞中MUC2的产生。
