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杀真菌剂Bac8c引发线粒体稳态的减弱和半胱天冬酶依赖性凋亡死亡。

Fungicide Bac8c triggers attenuation of mitochondrial homeostasis and caspase-dependent apoptotic death.

作者信息

Lee Heejeong, Lee Dong Gun

机构信息

School of Life Sciences, BK 21 Plus KNU BioResearch Group, College of Natural Sciences, Kyungpook National University, 80 Daehakro, Bukgu, Daegu, 41566, Republic of Korea.

School of Life Sciences, BK 21 Plus KNU BioResearch Group, College of Natural Sciences, Kyungpook National University, 80 Daehakro, Bukgu, Daegu, 41566, Republic of Korea.

出版信息

Biochimie. 2017 Feb;133:80-86. doi: 10.1016/j.biochi.2016.12.013. Epub 2016 Dec 25.

Abstract

Bac8c (RIWVIWRR-NH), an 8-mer peptide modified from amino acids 4-11 of Bac2a, shows broad-spectrum activity against pathogenic bacteria and yeast, and it has been the focus of attention owing to its low cost of synthesis. Although Bac8c is effective against Candida albicans, its mode of action needs to be investigated further. Bac8c causes yeast cell death in a dose-dependent manner by eliciting the production of reactive oxygen species, thereby attenuating the antioxidant defense system. It is also involved in Ca signaling, and produces apoptotic features, such as phosphatidylserine externalization and DNA fragmentation. Bac8c induces cell death by oxidative stress-dependent apoptotic death via disruption of mitochondrial homeostasis and metacaspase activation. This suggests that the concentration of Bac8c is important for the induction of apoptotic death, which is not necessarily accompanied by cell cycle arrest in C. albicans.

摘要

Bac8c(RIWVIWRR-NH)是一种从Bac2a的4-11位氨基酸修饰而来的八聚体肽,对病原菌和酵母具有广谱活性,且因其合成成本低而备受关注。尽管Bac8c对白色念珠菌有效,但其作用方式仍需进一步研究。Bac8c通过引发活性氧的产生以剂量依赖的方式导致酵母细胞死亡,从而削弱抗氧化防御系统。它还参与钙信号传导,并产生凋亡特征,如磷脂酰丝氨酸外翻和DNA片段化。Bac8c通过破坏线粒体稳态和metacaspase激活,经由氧化应激依赖性凋亡死亡诱导细胞死亡。这表明Bac8c的浓度对于诱导凋亡死亡很重要,而在白色念珠菌中凋亡死亡不一定伴随着细胞周期停滞。

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