Regulatory mechanism of the flavoprotein Tah18-dependent nitric oxide synthesis and cell death in yeast

Yoshikawa, Yasuhiro; Nasuno, Ryo; Kawahara, Nobuhiro; Nishimura, Akira; Watanabe, Dai; Takagi, Hiroshi

doi:10.1016/j.niox.2016.04.003

Cited by 24 publications

(28 citation statements)

References 34 publications

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“…It can affect DNA, enzymes, virulence factors, and the replication machinery 25 . To investigate change in NO levels caused by LBLP, a NO‐selective probe (DAF‐FM DA) that has been used to detect NO in yeast was used 14 . Incubated cells with LBLP caused significant changes in C. albicans NO levels (33.26%), indicating that NO is produced upon LBLP treatment.…”

Section: Resultsmentioning

confidence: 99%

“…Incubated cells with LBLP caused significant changes in C. albicans NO levels (33.26%), indicating that NO is produced upon LBLP treatment. NOS can be inhibited by L‐NAME to prevent the generation of NO radicals 14 . Pretreatment with the L‐NAME caused NO production to be reduced by 24.12% (Figure 1a).…”

Section: Resultsmentioning

confidence: 99%

“…In the current study, we investigated the effects of LBLP‐induced NO on cell death. LBLP‐induced NO decreased when treated with NOS inhibitor in C. albicans , which indicates that this fungus may produce NO by catalyzing the conversion of l ‐arginine into NO and l ‐citrulline 14,38 . These results prompted us to hypothesize that the enhanced intracellular antifungal activity of LBLP is mediated by increased NO.…”

Section: Discussionmentioning

confidence: 99%

“…After resuspending the cells in PBS, 4‐amino‐5‐methylamino‐2′,7′‐difluorofluorescein diacetate (DAF‐FM DA) (Molecular Probes, Eugene, OR) was added to a final concentration of 10 μM and incubated at 28°C for 30 min. Following centrifugation and resuspension in PBS, the samples were analyzed using a FACSVerse flow cytometer (Becton Dickinson, NJ) 14 …”

Section: Methodsmentioning

confidence: 99%

“…NO is produced by nitric oxide synthase (NOS), which catalyzes the conversion of l ‐arginine into NO and l ‐citrulline 13 . In yeast, NOS‐like enzyme has been identified and its activity is regulated in a manner similar to NOS in mammalian cells 14 . Relatively low concentrations of NO are crucial to facilitate signal transduction.…”

Section: Introductionmentioning

confidence: 99%

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Lactoferricin B like peptide triggers mitochondrial disruption‐mediated apoptosis by inhibiting respiration under nitric oxide accumulation inCandida albicans

2020

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Lactoferricin B like peptide triggers mitochondrial disruption‐mediated apoptosis by inhibiting respiration under nitric oxide accumulation inCandida albicans

2020

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Construction of Baker’s Yeast Strains with Enhanced Tolerance to Baking-Associated Stresses

Takagi

2017

Biotechnology of Yeasts and Filamentous Fungi

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Nitric oxide signaling in yeast

Astuti

Nasuno

Takagi

2016

Appl Microbiol Biotechnol

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As a cellular signaling molecule, nitric oxide (NO) is widely conserved from microorganisms, such as bacteria, yeasts, and fungi, to higher eukaryotes including plants and mammals. NO is mainly produced by NO synthase (NOS) or nitrite reductase (NIR) activity. There are several NO detoxification systems, including NO dioxygenase (NOD) and S-nitrosoglutathione reductase (GSNOR). NO homeostasis based on the balance between NO synthesis and degradation is important for the regulation of its physiological functions because an excess level of NO causes nitrosative stress due to the high reactivity of NO and NO-derived compounds. In yeast, NO may be involved in stress responses, but NO and its signaling have been poorly understood due to the lack of mammalian NOS orthologs in the genome. Even though the activities of NOS and NIR have been observed in yeast cells, the gene encoding NOS and the NO production mechanism catalyzed by NIR remain unclear. On the other hand, yeast cells employ NOD and GSNOR to maintain an intracellular redox balance following endogenous NO production, exogenous NO treatment, or environmental stresses. This article reviews NO metabolism (synthesis, degradation) and its regulation in yeast. The physiological roles of NO in yeast, including the oxidative stress response, are also discussed here. Such investigations into NO signaling are essential for understanding the NO-dependent genetic and physiological modulations. In addition to being responsible for the pathology and pharmacology of various degenerative diseases, NO signaling may be a potential target for the construction and engineering of industrial yeast strains.

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Regulatory mechanism of the flavoprotein Tah18-dependent nitric oxide synthesis and cell death in yeast

Cited by 24 publications

References 34 publications

Lactoferricin B like peptide triggers mitochondrial disruption‐mediated apoptosis by inhibiting respiration under nitric oxide accumulation inCandida albicans

Lactoferricin B like peptide triggers mitochondrial disruption‐mediated apoptosis by inhibiting respiration under nitric oxide accumulation inCandida albicans

Construction of Baker’s Yeast Strains with Enhanced Tolerance to Baking-Associated Stresses

Nitric oxide signaling in yeast

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