T‐2 Toxin‐Mediated β‐Arrestin‐1 O‐GlcNAcylation Exacerbates Glomerular Podocyte Injury via Regulating Histone Acetylation

Abstract: T‐2 toxin causes renal dysfunction with proteinuria and glomerular podocyte damage. This work explores the role of metabolic disorder/reprogramming‐mediated epigenetic modification in the progression of T‐2 toxin‐stimulated podocyte injury. A metabolomics experiment is performed to assess metabolic responses to T‐2 toxin infection in human podocytes. Roles of protein O‐linked‐N‐acetylglucosaminylation (O‐GlcNAcylation) in regulating T‐2 toxin‐stimulated podocyte injury in mouse and podocyte models are assessed. O‐GlcNAc target proteins are recognized by mass spectrometry and co‐immunoprecipitation experiments. Moreover, histone acetylation and autophagy levels are measured. T‐2 toxin infection upregulates glucose transporter type 1 (GLUT1) expression and enhances hexosamine biosynthetic pathway in glomerular podocytes, resulting in a significant increase in β‐arrestin‐1 O‐GlcNAcylation. Decreasing β‐arrestin‐1 or O‐GlcNAc transferase (OGT) effectively prevents T‐2 toxin‐induced renal dysfunction and podocyte injury. Mechanistically, O‐GlcNAcylation of β‐arrestin‐1 stabilizes β‐arrestin‐1 to activate the mammalian target of rapamycin (mTOR) pathway as well as to inhibit autophagy during podocyte injury by promoting H4K16 acetylation. To sum up, OGT‐mediated β‐arrestin‐1 O‐GlcNAcylation is a vital regulator in the development of T‐2 toxin‐stimulated podocyte injury via activating the mTOR pathway to suppress autophagy. Targeting β‐arrestin‐1 or OGT can be a potential therapy for T‐2 toxin infection‐associated glomerular injury, especially podocyte injury.

Objekt anzeigen

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch

Verweise und Beziehungen

• Erschienen in: T‐2 Toxin‐Mediated β‐Arrestin‐1 O‐GlcNAcylation Exacerbates Glomerular Podocyte Injury via Regulating Histone Acetylation ; day:11 ; month:12 ; year:2023 ; extent:17 ; Advanced science ; (11.12.2023) (gesamt 17)

Beteiligte, Orts- und Zeitangaben

• Urheber: Li, Tushuai ; Sun, Wenxue ; Zhu, Shenglong ; He, Chengsheng ; Chang, Tong ; Zhang, Jie ; Chen, Yongquan

Weitere Informationen

• DOI: 10.1002/advs.202307648
• URN: urn:nbn:de:101:1-2023121214242698235195
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.