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Deubiquitinating Enzyme USP19 Regulates Ferroptosis and Mitochondrial Damage in SH-SY5Y Cells by Targeting the NOX4 Protein.
Yu, Wenzhen; Zhuang, Shuting; Zhan, Mengxiong; Chen, Yong; Zhang, Jieping; Chen, Ling; Tu, Chunxiang; Zheng, Linfei; Chen, Shi.
Afiliación
  • Yu W; College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fu Zhou, China.
  • Zhuang S; College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fu Zhou, China.
  • Zhan M; Department of Neurosurgery, Fuzhou Second Hospital, Fu Zhou, China.
  • Chen Y; College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fu Zhou, China.
  • Zhang J; College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fu Zhou, China.
  • Chen L; College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fu Zhou, China.
  • Tu C; College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fu Zhou, China.
  • Zheng L; Department of Neurosurgery, Fuzhou Second Hospital, Fu Zhou, China.
  • Chen S; Department of Neurosurgery, Fuzhou Second Hospital, Fu Zhou, China.
J Alzheimers Dis ; 100(3): 799-808, 2024.
Article en En | MEDLINE | ID: mdl-38943386
ABSTRACT

Background:

Ferroptosis is extremely relevant to the progression of neurodegenerative pathologies such as Alzheimer's disease (AD). Ubiquitin-specific proteases (USP) can affect the NADPH oxidase family.

Objective:

Our study aimed to elucidate the potential role and molecular basis of a certain USP19 in reducing ferroptosis and mitochondrial injury in AD cells by targeting NOX4 stability.

Methods:

The deubiquitinase USP family gene USP19, which affects the stability of NOX4 protein, was first screened. The cell model of AD was constructed after interfering with SH-SY5Y cells by Aß1-40, and then SH-SY5Y cells were infected with lentiviral vectors to knock down USP19 and overexpress NOX4, respectively. Finally, the groups were tested for cell viability, changes in cellular mitochondrial membrane potential, lipid reactive oxygen species, intracellular iron metabolism, and NOX4, Mf1, Mf2, and Drp1 protein expression.

Results:

5 µmol/L Aß1-40 intervened in SH-SY5Y cells for 24 h to construct a cell model of AD. Knockdown of USP19 decreased the expression of NOX4 protein, promoted the expression of mitochondrial fusion proteins Mnf1 and Mnf2, and inhibited the expression of the splitting protein Drp1. Furthermore, USP19 knockdown decreased mitochondrial membrane potential, SOD, MDA, intracellular iron content and increased GSH/GSSG ratio in SH-SY5Y cells. Our study revealed that NOX4 protein interacts with USP19 and knockdown of USP19 enhanced ubiquitination to maintain NOX4 protein stability.

Conclusions:

USP19 attenuates mitochondrial damage in SH-SY5Y cells by targeting NOX4 protein with Aß1-40.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos beta-Amiloides / NADPH Oxidasa 4 / Ferroptosis / Mitocondrias Límite: Humans Idioma: En Revista: J Alzheimers Dis Asunto de la revista: GERIATRIA / NEUROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos beta-Amiloides / NADPH Oxidasa 4 / Ferroptosis / Mitocondrias Límite: Humans Idioma: En Revista: J Alzheimers Dis Asunto de la revista: GERIATRIA / NEUROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos