School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan.
Medical Mycology Research Center, Chiba University, Chiba, Japan.
Med Mycol. 2020 Jul 1;58(5):679-689. doi: 10.1093/mmy/myz105.
NADPH oxidases (Nox) generate reactive oxygen species (ROS) such as superoxide anion radical (O2-) and hydrogen peroxide (H2O2). The pathogenic fungi Candida albicans and Candida glabrata enhance cellular transglutaminase 2 (TG2) activity levels in co-cultured human hepatic cells in a ROS-mediated manner. Deletion of NOX1 (CgNOX1) in C. glabrata blocks the ability of C. glabrata to induce TG2 activity. Here, we investigated whether Nox proteins from C. albicans and Saccharomyces cerevisiae are related with induction of TG2 activity in hepatic cells. C. albicans CFL11 (CaCFL11) was identified as a key factor in this fungus for hepatic TG2 induction in the co-cultures. The cfl11 mutant of C. albicans did not induce TG2 activity in hepatocytes. In addition, overexpression of YNO1, a homolog of CgNOX1, in S. cerevisiae led to induction of ROS generation and TG2 activity in hepatic cells in co-incubation experiments. These findings indicated that a fungal Nox plays a role in enhancing TG2 activity in human hepatocytes and leads to apoptosis.
NADPH 氧化酶（Nox）产生活性氧（ROS），如超氧阴离子自由基（O2-）和过氧化氢（H2O2）。致病性真菌白色念珠菌和光滑念珠菌以 ROS 介导的方式增强共培养的人肝细胞中的细胞转谷氨酰胺酶 2（TG2）活性水平。在光滑念珠菌中敲除 NOX1（CgNOX1）会阻止光滑念珠菌诱导 TG2 活性的能力。在这里，我们研究了来自白色念珠菌和酿酒酵母的 Nox 蛋白是否与诱导肝细胞中 TG2 活性有关。鉴定出白色念珠菌 CFL11（CaCFL11）是该真菌在共培养物中诱导肝 TG2 的关键因素。白色念珠菌的 cfl11 突变体不会诱导肝细胞中的 TG2 活性。此外，在酿酒酵母中过表达 CgNOX1 的同源物 YNO1 导致在共孵育实验中 ROS 的产生和肝细胞中 TG2 活性的诱导。这些发现表明真菌 Nox 在增强人肝细胞中的 TG2 活性并导致细胞凋亡方面发挥作用。
