Lysosome-associated membrane protein-2 deficiency increases the risk of reactive oxygen species-induced ferroptosis in retinal pigment epithelial cells

Jong Jer Lee, Kenji Ishihara, Shoji Notomi, Nikolaos E. Efstathiou, Takashi Ueta, Daniel Maidana, Xiaohong Chen, Yasuhiro Iesato, Alberto Caligiana, Demetrios G. Vavvas

研究成果: ジャーナルへの寄稿記事

抄録

Lysosome-associated membrane protein-2 (LAMP2), is a highly glycosylated lysosomal membrane protein involved in chaperone mediated autophagy. Mutations of LAMP2 cause the classic triad of myopathy, cardiomyopathy and encephalopathy of Danon disease (DD). Additionally, retinopathy has also been observed in young DD patients, leading to vision loss. Emerging evidence show LAMP2-deficiency to be involved in oxidative stress (ROS) but the mechanism remains obscure. In the present study, we found that tert-butyl hydroperoxide or antimycin A induced more cell death in LAMP2 knockdown (LAMP2-KD) than in control ARPE-19 cells. Mechanistically, LAMP2-KD reduced the concentration of cytosolic cysteine, resulting in low glutathione (GSH), inferior antioxidant capability and mitochondrial lipid peroxidation. ROS induced RPE cell death through ferroptosis. Inhibition of glutathione peroxidase 4 (GPx4) increased lethality in LAMP2-KD cells compared to controls. Cysteine and glutamine supplementation restored GSH and prevented ROS-induced cell death of LAMP2-KD RPE cells.

元の言語英語
ページ(範囲)414-419
ページ数6
ジャーナルBiochemical and Biophysical Research Communications
521
発行部数2
DOI
出版物ステータス出版済み - 1 8 2020

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Lysosome-Associated Membrane Glycoproteins
Protein Deficiency
Retinal Pigments
Reactive Oxygen Species
Epithelial Cells
Glycogen Storage Disease Type IIb
Cell death
Cell Death
phospholipid-hydroperoxide glutathione peroxidase
Cysteine
Antimycin A
tert-Butylhydroperoxide
Oxidative stress
Autophagy
Brain Diseases
Muscular Diseases
Glutamine
Cardiomyopathies
Lipid Peroxidation
Glutathione

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

これを引用

Lysosome-associated membrane protein-2 deficiency increases the risk of reactive oxygen species-induced ferroptosis in retinal pigment epithelial cells. / Lee, Jong Jer; Ishihara, Kenji; Notomi, Shoji; Efstathiou, Nikolaos E.; Ueta, Takashi; Maidana, Daniel; Chen, Xiaohong; Iesato, Yasuhiro; Caligiana, Alberto; Vavvas, Demetrios G.

:: Biochemical and Biophysical Research Communications, 巻 521, 番号 2, 08.01.2020, p. 414-419.

研究成果: ジャーナルへの寄稿記事

Lee, Jong Jer ; Ishihara, Kenji ; Notomi, Shoji ; Efstathiou, Nikolaos E. ; Ueta, Takashi ; Maidana, Daniel ; Chen, Xiaohong ; Iesato, Yasuhiro ; Caligiana, Alberto ; Vavvas, Demetrios G. / Lysosome-associated membrane protein-2 deficiency increases the risk of reactive oxygen species-induced ferroptosis in retinal pigment epithelial cells. :: Biochemical and Biophysical Research Communications. 2020 ; 巻 521, 番号 2. pp. 414-419.
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abstract = "Lysosome-associated membrane protein-2 (LAMP2), is a highly glycosylated lysosomal membrane protein involved in chaperone mediated autophagy. Mutations of LAMP2 cause the classic triad of myopathy, cardiomyopathy and encephalopathy of Danon disease (DD). Additionally, retinopathy has also been observed in young DD patients, leading to vision loss. Emerging evidence show LAMP2-deficiency to be involved in oxidative stress (ROS) but the mechanism remains obscure. In the present study, we found that tert-butyl hydroperoxide or antimycin A induced more cell death in LAMP2 knockdown (LAMP2-KD) than in control ARPE-19 cells. Mechanistically, LAMP2-KD reduced the concentration of cytosolic cysteine, resulting in low glutathione (GSH), inferior antioxidant capability and mitochondrial lipid peroxidation. ROS induced RPE cell death through ferroptosis. Inhibition of glutathione peroxidase 4 (GPx4) increased lethality in LAMP2-KD cells compared to controls. Cysteine and glutamine supplementation restored GSH and prevented ROS-induced cell death of LAMP2-KD RPE cells.",
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AU - Efstathiou, Nikolaos E.

AU - Ueta, Takashi

AU - Maidana, Daniel

AU - Chen, Xiaohong

AU - Iesato, Yasuhiro

AU - Caligiana, Alberto

AU - Vavvas, Demetrios G.

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