Next Article in Journal
Phytoconstituents of Androstachys johnsonii Prain Prevent Reactive Oxygen Species Production and Regulate the Expression of Inflammatory Mediators in LPS-Stimulated RAW 264.7 Macrophages
Next Article in Special Issue
Studying the Changes in Physical Functioning and Oxidative Stress-Related Molecules in People Living with HIV after Switching from Triple to Dual Therapy
Previous Article in Journal
Light-Induced Antioxidant Phenolic Changes among the Sprouts of Lentil Cultivar
Previous Article in Special Issue
Development of New Resolvin D1 Analogues for Osteoarthritis Therapy: Acellular and Computational Approaches to Study Their Antioxidant Activities
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Antioxidants
Volume 13
Issue 4
10.3390/antiox13040400
antioxidants-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
Correction published on 10 February 2026, see Antioxidants 2026, 15(2), 228.
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Glutathione Induces Keap1 S-Glutathionylation and Mitigates Oscillating Glucose-Induced β-Cell Dysfunction by Activating Nrf2

by
Xiufang Chen
1,*,†,
Qian Zhou
1,†,
Huamin Chen
1,
Juan Bai
1,
Ruike An
1,
Keyi Zhang
1,
Xinyue Zhang
2,
Hui An
2,
Jitai Zhang
2,
Yongyu Wang
3 and
Ming Li
2,*
1
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, China
2
Cardiac Regeneration Research Institute, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, China
3
Institute of Hypoxia Medicine, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Antioxidants 2024, 13(4), 400; https://doi.org/10.3390/antiox13040400
Submission received: 3 March 2024 / Revised: 20 March 2024 / Accepted: 25 March 2024 / Published: 27 March 2024 / Corrected: 10 February 2026
(This article belongs to the Special Issue Antioxidants and Oxidative Stress in the Development of Diseases and Therapy)
Browse Figures
Versions Notes

Abstract

Glutathione (GSH), a robust endogenous antioxidant, actively participates in the modulation of the redox status of cysteine residues in proteins. Previous studies have indicated that GSH can prevent β-cell failure and prediabetes caused by chronic oscillating glucose (OsG) administration. However, the precise mechanism underlying the protective effect is not well understood. Our current research reveals that GSH is capable of reversing the reduction in Nrf2 levels, as well as downstream genes Grx1 and HO-1, in the islet β-cells of rats induced by chronic OsG. In vitro experiments have further demonstrated that GSH can prevent β-cell dedifferentiation, apoptosis, and impaired insulin secretion caused by OsG. Additionally, GSH facilitates the translocation of Nrf2 into the nucleus, resulting in an upregulation of Nrf2-targeted genes such as GCLC, Grx1, HO-1, and NQO1. Notably, when the Nrf2 inhibitor ML385 is employed, the effects of GSH on OsG-treated β-cells are abrogated. Moreover, GSH enhances the S-glutathionylation of Keap1 at Cys273 and Cys288, but not Cys151, in OsG-treated β-cells, leading to the dissociation of Nrf2 from Keap1 and facilitating Nrf2 nuclear translocation. In conclusion, the protective role of GSH against OsG-induced β-cell failure can be partially attributed to its capacity to enhance Keap1 S-glutathionylation, thereby activating the Nrf2 signaling pathway. These findings provide novel insights into the prevention and treatment of β-cell failure in the context of prediabetes/diabetes, highlighting the potential of GSH.
Keywords: prediabetes; glucotoxicity; β-cell; glutathione; S-glutathionylation; Keap1; Nrf2 prediabetes; glucotoxicity; β-cell; glutathione; S-glutathionylation; Keap1; Nrf2

Share and Cite

MDPI and ACS Style

Chen, X.; Zhou, Q.; Chen, H.; Bai, J.; An, R.; Zhang, K.; Zhang, X.; An, H.; Zhang, J.; Wang, Y.; et al. Glutathione Induces Keap1 S-Glutathionylation and Mitigates Oscillating Glucose-Induced β-Cell Dysfunction by Activating Nrf2. Antioxidants 2024, 13, 400. https://doi.org/10.3390/antiox13040400

AMA Style

Chen X, Zhou Q, Chen H, Bai J, An R, Zhang K, Zhang X, An H, Zhang J, Wang Y, et al. Glutathione Induces Keap1 S-Glutathionylation and Mitigates Oscillating Glucose-Induced β-Cell Dysfunction by Activating Nrf2. Antioxidants. 2024; 13(4):400. https://doi.org/10.3390/antiox13040400

Chicago/Turabian Style

Chen, Xiufang, Qian Zhou, Huamin Chen, Juan Bai, Ruike An, Keyi Zhang, Xinyue Zhang, Hui An, Jitai Zhang, Yongyu Wang, and et al. 2024. "Glutathione Induces Keap1 S-Glutathionylation and Mitigates Oscillating Glucose-Induced β-Cell Dysfunction by Activating Nrf2" Antioxidants 13, no. 4: 400. https://doi.org/10.3390/antiox13040400

APA Style

Chen, X., Zhou, Q., Chen, H., Bai, J., An, R., Zhang, K., Zhang, X., An, H., Zhang, J., Wang, Y., & Li, M. (2024). Glutathione Induces Keap1 S-Glutathionylation and Mitigates Oscillating Glucose-Induced β-Cell Dysfunction by Activating Nrf2. Antioxidants, 13(4), 400. https://doi.org/10.3390/antiox13040400

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop