SSBP1 drives high fructose-induced glomerular podocyte ferroptosis via activating DNA-PK/p53 pathway
2022
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- Autor(en) / Beteiligte
- Titel
- SSBP1 drives high fructose-induced glomerular podocyte ferroptosis via activating DNA-PK/p53 pathway
- Ist Teil von
- Redox biology, 2022-06, Vol.52, p.102303-102303, Article 102303
- Ort / Verlag
- Netherlands: Elsevier B.V
- Erscheinungsjahr
- 2022
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- High fructose consumption is a significant risking factor for glomerular podocyte injury. However, the causes of high fructose-induced glomerular podocyte injury are still unclear. In this study, we reported a novel mechanism by which high fructose induced ferroptosis, a newly form of programmed cell death, in glomerular podocyte injury. We performed quantitative proteomic analysis in glomeruli of high fructose-fed rats to identify key regulating proteins involved in glomerular injury, and found that mitochondrial single-strand DNA-binding protein 1 (SSBP1) was markedly upregulated. Depletion of SSBP1 could alleviate high fructose-induced ferroptotic cell death in podocytes. Subsequently, we found that SSBP1 positively regulated a transcription factor p53 by interacting with DNA-dependent protein kinase (DNA-PK) and p53 to drive ferroptosis in high fructose-induced podocyte injury. Mechanically, SSBP1 activated DNA-PK to induce p53 phosphorylation at serine 15 (S15) to promote the nuclear accumulation of p53, and thereby inhibited expression of ferroptosis regulator solute carrier family 7 member 11 (SLC7A11) in high fructose-exposed podocytes. Natural antioxidant pterostilbene was showed to downregulate SSBP1 and then inhibit DNA-PK/p53 pathway in its alleviation of high fructose-induced glomerular podocyte ferroptosis and injury. This study identified SSBP1 as a novel intervention target against high fructose-induced podocyte ferroptosis and suggested that the suppression of SSBP1 by pterostilbene may be a potential therapy for the treatment of podocyte ferroptosis in glomerular injury. [Display omitted]
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2213-2317eISSN: 2213-2317DOI: 10.1016/j.redox.2022.102303Titel-ID: cdi_doaj_primary_oai_doaj_org_article_dcf9afb8514b4139854518fbe9886beb
- Format
- –
- Schlagworte
- Animals, DNA - metabolism, DNA-Activated Protein Kinase - metabolism, DNA-Binding Proteins - metabolism, DNA-PK, Female, Ferroptosis, Fructose - adverse effects, High fructose, Humans, Kidney Diseases - metabolism, Male, Mitochondrial Proteins - metabolism, p53, Podocyte ferroptosis, Podocytes - metabolism, Proteomics, Pterostilbene, Rats, Research Paper, SSBP1, Tumor Suppressor Protein p53 - genetics, Tumor Suppressor Protein p53 - metabolism