Fungus-derived hydroxyl radicals kill hepatic cells by enhancing nuclear transglutaminase.
Fungus-derived hydroxyl radicals kill hepatic cells by enhancing nuclear transglutaminase.
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真菌衍生的羟基自由基通过增强核转谷氨酰胺酶杀死肝细胞
DOI：
10.1038/s41598-017-04630-8
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发表时间：
2017-07-06
影响因子：
4.6
通讯作者：
Kojima S
中科院分区：
文献类型：
--
作者：
Shrestha R;Shrestha R;Qin XY;Kuo TF;Oshima Y;Iwatani S;Teraoka R;Fujii K;Hara M;Li M;Takahashi-Nakaguchi A;Chibana H;Lu J;Cai M;Kajiwara S;Kojima S
我们先前报道了诱导核转氨酶（TG）2活性的重要性，这导致肝细胞死亡，在乙醇诱导的肝损伤。在这里，我们发现，无论是人肝细胞或小鼠原代肝细胞来源于野生型，但不是TG 2 −/−小鼠与致病真菌白色念珠菌和C。glabrata，而不是面包酵母酿酒酵母，诱导宿主细胞的细胞死亡，通过增强细胞，特别是核，TG活性。进一步的药理学和遗传学方法表明，这种现象部分是由活性氧（ROS），如羟基自由基的产生介导的，如荧光探针和电子自旋共振检测。活性氧清除剂，N-乙酰半胱氨酸，主要在细胞核中阻断增强的TG活性并抑制细胞死亡。相反，C. glabrata nox-1编码ROS生成酶，导致不能诱导相同现象的菌株。在C.白色念珠菌感染的小鼠。抗氧化剂玉米肽馏分抑制肝细胞中的这些现象。这些结果解决了ROS产生病原体在诱导核TG 2相关肝损伤中的影响，这为预防和治疗酒精性肝病提供了新的治疗靶点。
We previously reported the importance of induced nuclear transglutaminase (TG) 2 activity, which results in hepatic cell death, in ethanol-induced liver injury. Here, we show that co-incubation of either human hepatic cells or mouse primary hepatocytes derived from wild-type but not TG2−/−mice with pathogenic fungiCandida albicansandC. glabrata, but not baker’s yeastSaccharomyces cerevisiae, induced cell death in host cells by enhancing cellular, particularly nuclear, TG activity. Further pharmacological and genetic approaches demonstrated that this phenomenon was mediated partly by the production of reactive oxygen species (ROS) such as hydroxyl radicals, as detected by a fluorescent probe and electron spin resonance. A ROS scavenger, N-acetyl cysteine, blocked enhanced TG activity primarily in the nuclei and inhibited cell death. In contrast, deletion ofC. glabrata nox-1, which encodes a ROS-generating enzyme, resulted in a strain that failed to induce the same phenomena. A similar induction of hepatic ROS and TG activities was observed inC. albicans-infected mice. An antioxidant corn peptide fraction inhibited these phenomena in hepatic cells. These results address the impact of ROS-generating pathogens in inducing nuclear TG2-related liver injuries, which provides novel therapeutic targets for preventing and curing alcoholic liver disease.
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影响因子：
3.4
作者：
Brunke S;Hube B
通讯作者：
Hube B
DOI：
10.1016/j.jcmgh.2015.04.003
发表时间：
2015-05-01
影响因子：
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作者：
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通讯作者：
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作者：
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DOI：
10.1016/s0006-291x(03)00835-0
发表时间：
2003-06-06
影响因子：
3.1
作者：
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通讯作者：
Ha, KS