Exogenous H2S reduces oxidative stress induced by lipid mixture in HepG2 cells through USP22/SIRT1 axis
Open accessAbstract
H 2 S signal transduction involves various physiological processes, including promoting vasodilation, regulating lipid metabolism, inducing angiogenesis, improving oxidative stress and inflammatory response, and avoiding cell apoptosis. Oxidative stress is an important mechanism that causes the pathological progression of NAFLD. However, the effect and specific mechanism of exogenous H 2 S on oxidative stress in NAFLD are still unclear. Here, we investigated the specific regulatory mechanism of exogenous H 2 S on oxidative stress and inflammation induced by LM in HepG2 cells. HepG2 cells were stimulated with LM with or without GYY4137 (200 µM) treatment for 24 h. The levels of MDA, SOD, ROS, TNF-α, IL-6, and antioxidant related proteins of cells were detected. We found exogenous H 2 S remarkably reduced the levels of MDA, ROS, TNF-α and IL-6 and elevated SOD contents as well as the expression of antioxidant-related proteins in LM-induced HepG2 cells. Moreover, exogenous H 2 S improved the expression of USP22 protein in LM-induced HepG2 cells and inhibited the ubiquitination degradation of SIRT1 through USP22. After USP22 was knocked down, the efficacy of exogenous H 2 S on mitigating LM-induced oxidative damage and inflammatory reaction in HepG2 cells had been weakened. In conclusion, exogenous H 2 S inhibited SIRT1 ubiquitination degradation through USP22, thereby alleviating LM-induced oxidative stress and inflammatory responses in HepG2 cells.
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HepG2 is suitable for primary testing of intracellular TG and lipid droplet reduction, normalization of ER stress/ROS markers, restoration of mitochondrial function in lipotoxicity, and effects on transcriptional programs.
“Thus, HepG2 is suitable for primary testing of intracellular TG and lipid droplet reduction, normalization of ER stress/ROS markers, restoration of mitochondrial function in lipotoxicity, and effects on transcriptional programs (lipogenesis, β-oxidation, inflammation) [80,91,92,93,94].”
From The HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease (2026) · cites this paper as [92]
The Results (page not provided) show that lipid-mixture-treated HepG2 cells were used to assess lipid droplets, ROS, antioxidant markers and inflammatory factors, and that GYY4137 improved several of these measures. The paper does not establish this full testing scope: the cited results do not assess intracellular triglycerides, restoration of mitochondrial function, or transcriptional programs. ER stress is mentioned in the Introduction (page not provided) in connection with previous research, not measured in this study. (LLM, conf=0.88)
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The HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease
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- Authors
- Cui, X., Li, C., He, S., & Li, Y.
- Affiliations
- Second Affiliated Hospital of Xi'an Jiaotong University (CN)
- First Affiliated Hospital of Xi'an Jiaotong University (CN)
- Corresponding author
- He, Shuixiang
- Li, Yarui
- Venue
- Scientific Reports
- Published
- 2025-07-02
- Volume
- 15
- Issue
- 1
- Pages
- 23129-23129
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC12214682
- OpenAlex
- W4411856733
- Cited by
- 6
- References
- 32
- Citations by year
- 2026: 5 · 2025: 1
- FWCI
- 1.93
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Scientific Reports (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- the Key Research and Development Program of Shaanxi (2021ZDLSF02-06)
- the National Natural Science Foundation of China (No.82303169)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Keywords
- hydrogen sulfide, oxidative stress, non-alcoholic fatty liver disease, USP22, SIRT1, ubiquitination, lipid peroxidation, inflammation, TNF-α, interleukin-6, superoxide dismutase, GYY4137, HepG2 cells
- MeSH terms
- Humans, Lipids, Tumor Necrosis Factor-alpha, Signal Transduction, Reactive Oxygen Species, Oxidative Stress, Ubiquitin Thiolesterase, Ubiquitination, Sirtuin 1, Hep G2 Cells
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