Streptolysin S induces mitochondrial damage and macrophage death through inhibiting degradation of glycogen synthase kinase-3β in Streptococcus pyogenes infection

Nina Tsao, Chih Feng Kuo, Miao Hui Cheng, Wei Chen Lin, Chiou Feng Lin, Yee Shin Lin

研究成果: 雜誌貢獻文章

2 引文 斯高帕斯(Scopus)

摘要

Group A Streptococcus (GAS) infection is associated with a variety of human diseases. Previous studies indicate GAS infection leads to RAW264.7 cell death, but the mechanism is unclear. Here, analyzing the timing of reactive oxygen species (ROS) production and using mitochondrial ROS scavenger, we found the wild type GAS-induced RAW264.7 cell death was associated with mitochondrial ROS. The wild type GAS infection could activate glycogen synthase kinase-3β (GSK-3β). Inhibition of GSK-3β activity by lithium chloride or decreasing GSK-3β expression by lentivirus-mediated short hairpin RNA for GSK-3β could not only decrease the wild type GAS-induced mitochondrial ROS generation, mitochondria damage and cell death, but also reduced GAS intracellular replication. Streptolysin S (SLS), a GAS toxin, played the important role on GAS-induced macrophage death. Compared to the wild type GAS with its isogenic sagB mutant (SLS mutant)-infected macrophages, we found sagB mutant infection caused less mitochondrial ROS generation and cell death than those of the wild type GAS-infected ones. Furthermore, the sagB mutant, but not the wild type or the sagB-complementary mutant, could induce GSK-3β degradation via a proteasome-dependent pathway. These results suggest that a new mechanism of SLS-induced macrophage death was through inhibiting GSK-3β degradation and further enhancing mitochondrial damage.
原文英語
文章編號5371
期刊Scientific Reports
9
發行號1
DOIs
出版狀態已發佈 - 十二月 1 2019

ASJC Scopus subject areas

  • General

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