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博士論文 / Roles of vacuolar H+-ATPase in the oxidative stress response of Candida glabrata 病原真菌Candida glabrataの液胞膜 H+-ATPaseが酸化ストレス応答に及ぼす影響

著者

書誌事項

タイトル

Roles of vacuolar H+-ATPase in the oxidative stress response of Candida glabrata

タイトル別名

病原真菌Candida glabrataの液胞膜 H+-ATPaseが酸化ストレス応答に及ぼす影響

著者名

西川博

学位授与大学

Nagasaki University (長崎大学) (大学ID:0073) (CAT機関ID:KI000877)

取得学位

博士(医学)

学位授与番号

乙医歯薬第50号

学位授与年月日

2017-09-06

注記・抄録

Vacuolar H+-ATPase (V-ATPase) is responsible for the acidification of eukaryotic intracellular compartments and plays an important role in oxidative stress response (OSR), but its molecular bases are largely unknown. Here, we investigated how V-ATPase is involved in the OSR by using a strain lacking VPH2, which encodes an assembly factor of V-ATPase, in the pathogenic fungus Candida glabrata. The loss of Vph2 resulted in increased H2O2 sensitivity and intracellular reactive oxygen species (ROS) level independently of mitochondrial functions. The Δvph2 mutant also displayed growth defects under alkaline conditions accompanied by the accumulation of intracellular ROS and these phenotypes were recovered in the presence of the ROS scavenger N-acetyl-l-cysteine. Both expression and activity levels of mitochondrial manganese superoxide dismutase (Sod2) and catalase (Cta1) were decreased in the Δvph2 mutant. Phenotypic analyses of strains lacking and overexpressing these genes revealed that Sod2 and Cta1 play a predominant role in endogenous and exogenous OSR, respectively. Furthermore, supplementation of copper and iron restored the expression of SOD2 specifically in the Δvph2 mutant, suggesting that the homeostasis of intracellular cupper and iron levels maintained by V-ATPase was important for the Sod2-mediated OSR. This report demonstrates novel roles of V-ATPase in the OSR in C. glabrata.

開始ページ : fow054

元資料の権利情報 : © FEMS 2016. All rights reserved.

元資料の権利情報 : This is a pre-copyedited, author-produced version of an article accepted for publication in FEMS Yeast Research following peer review. The version of record FEMS Yeast Research, 16(5), fow054; 2016 is available online at: http://dx.doi.org/10.1093/femsyr/fow054.

Vacuolar H+-ATPase (V-ATPase) is responsible for the acidification of eukaryotic intracellular compartments and plays an important role in oxidative stress response (OSR), but its molecular bases are largely unknown. Here, we investigated how V-ATPase is involved in the OSR by using a strain lacking VPH2, which encodes an assembly factor of V-ATPase, in the pathogenic fungus Candida glabrata. The loss of Vph2 resulted in increased H2O2 sensitivity and intracellular reactive oxygen species (ROS) level independently of mitochondrial functions. The Δvph2 mutant also displayed growth defects under alkaline conditions accompanied by the accumulation of intracellular ROS and these phenotypes were recovered in the presence of the ROS scavenger N-acetyl-l-cysteine. Both expression and activity levels of mitochondrial manganese superoxide dismutase

(Sod2) and catalase (Cta1) were decreased in the Δvph2 mutant. Phenotypic analyses of strains lacking and overexpressing these genes revealed that Sod2 and Cta1 play a predominant role in endogenous and exogenous OSR, respectively. Furthermore, supplementation of copper and iron restored the expression of SOD2 specifically in the Δvph2 mutant, suggesting that the homeostasis of intracellular cupper and iron levels maintained by V-ATPase was important for the Sod2-mediated OSR. This report demonstrates novel roles of V-ATPase in the OSR in C. glabrata.

キーワード

superoxide dismutase, Candida glabrata, vacuolar H+-ATPase, catalase, oxidative stress response

各種コード

NII論文ID(NAID)

500001045174

NII著者ID(NRID)
  • 8000001153853
DOI (出版社)

10.1093/femsyr/fow054

DOI

info:doi/10.1093/femsyr/fow054

本文言語コード

eng

データ提供元

機関リポジトリ / NDLデジタルコレクション

外部リンク

DOI

博士論文 / 長崎大学 / 医学

博士論文 / 長崎大学

博士論文 / 医学

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