Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba 271-8587, Japan.
J Dent Res. 2010 Jul;89(7):689-94. doi: 10.1177/0022034510365456. Epub 2010 May 3.
Reactive oxygen species (ROS) are essential for the induction of T-cell apoptosis by butyric acid, an extracellular metabolite of periodontopathic bacteria. To determine the involvement of oxidative stress in apoptosis pathways, we investigated the contribution of ROS in mitochondrial signaling pathways, death-receptor-initiated signaling pathway, and endoplasmic reticulum stress in butyric-acid-induced T-cell apoptosis. N-acetyl-L-Cysteine (NAC) abrogated mitochondrial injury, cytochrome c, AIF, and Smac release, and Bcl-2 and Bcl-xL suppression and Bax and Bad activation induced by butyric acid. However, the decrease in cFLIP expression by butyric acid was not restored by treatment with NAC; increases in caspase-4 and -10 activities by butyric acid were completely abrogated by NAC. NAC also affected the elevation of GRP78 and CHOP/GADD153 expression by butyric acid. These results suggest that butyric acid is involved in mitochondrial-dysfunction- and endoplasmic reticulum stress-mediated apoptosis in human Jurkat T-cells via a ROS-dependent mechanism.
活性氧（ROS）对于牙周病病原体的细胞外代谢产物丁酸诱导 T 细胞凋亡至关重要。为了确定氧化应激在凋亡途径中的作用，我们研究了 ROS 在线粒体信号通路、死亡受体起始信号通路和内质网应激中的作用，以研究丁酸诱导的 T 细胞凋亡。N-乙酰-L-半胱氨酸（NAC）可阻断丁酸诱导的线粒体损伤、细胞色素 c、AIF 和 Smac 的释放，以及 Bcl-2 和 Bcl-xL 的抑制和 Bax 和 Bad 的激活。然而，丁酸引起的 cFLIP 表达下降不能通过 NAC 恢复；NAC 完全阻断了丁酸引起的 caspase-4 和 -10 活性的增加。NAC 还影响了丁酸引起的 GRP78 和 CHOP/GADD153 表达的升高。这些结果表明，丁酸通过 ROS 依赖性机制参与了人 Jurkat T 细胞中线粒体功能障碍和内质网应激介导的凋亡。
