Nitric oxide (NO) is a potentially powerful weapon against Candida albicans, and the regulation of intracellular NO levels is therefore important for controlling its physiological functions. Lactoferricin B like peptide (LBLP) is a 23‐mer antimicrobial peptide (AMP) derived from the Scolopendra subspinipes mutilans. We confirmed that LBLP treatment led to the generation of endogenous NO in C. albicans, which was associated with the NO synthase pathway. Here, we examined the antifungal activity of LBLP with focus on intracellular NO. Total glutathione levels were measured to evaluate cellular defense capacity against NO. LBLP decreased total glutathione levels, leading to nitrosative stress. LBLP also inhibited mitochondrial respiration and altered the NAD+/NADH ratios. Inhibition of mitochondrial respiration induced mitochondrial membrane depolarization, thus leading to calcium homeostasis disruption and mitochondrial superoxide anion accumulation. Consequently, treatment of C. albicans with LBLP resulted in apoptosis. These physiological changes were attenuated when NO generation was inhibited. Our data strongly indicate that LBLP mediates apoptosis by affecting intracellular NO homeostasis. These results on antifungal activity of LBLP and its mechanism indicate the therapeutic promise of this AMP and support the role of NO in cell death regulation.

中文翻译：

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乳铁蛋白 B 样肽通过抑制白色念珠菌中一氧化氮积累下的呼吸来触发线粒体破坏介导的细胞凋亡

一氧化氮 (NO) 是对抗白色念珠菌的潜在强大武器，因此调节细胞内 NO 水平对于控制其生理功能很重要。乳铁蛋白 B 样肽 (LBLP) 是一种 23 聚体抗菌肽 (AMP)，来源于 Scolopendra subspinipes muutilans。我们证实 LBLP 处理导致白色念珠菌中内源性 NO 的产生，这与 NO 合酶途径有关。在这里，我们检查了 LBLP 的抗真菌活性，重点是细胞内 NO。测量总谷胱甘肽水平以评估细胞对 NO 的防御能力。LBLP 降低总谷胱甘肽水平，导致亚硝化应激。LBLP 还抑制线粒体呼吸并改变 NAD+/NADH 比率。抑制线粒体呼吸诱导线粒体膜去极化，从而导致钙稳态破坏和线粒体超氧阴离子积累。因此，用 LBLP 处理白色念珠菌导致细胞凋亡。当 NO 生成受到抑制时，这些生理变化就会减弱。我们的数据强烈表明 LBLP 通过影响细胞内 NO 稳态介导细胞凋亡。这些关于 LBLP 抗真菌活性及其机制的结果表明了这种 AMP 的治疗前景，并支持 NO 在细胞死亡调节中的作用。我们的数据强烈表明 LBLP 通过影响细胞内 NO 稳态介导细胞凋亡。这些关于 LBLP 抗真菌活性及其机制的结果表明了这种 AMP 的治疗前景，并支持 NO 在细胞死亡调节中的作用。我们的数据强烈表明 LBLP 通过影响细胞内 NO 稳态介导细胞凋亡。这些关于 LBLP 抗真菌活性及其机制的结果表明了这种 AMP 的治疗前景，并支持 NO 在细胞死亡调节中的作用。