ArticleEnvironmental science and pollution research international2021
MEHP induces pyroptosis and autophagy alternation by cathepsin B activation in INS-1 cells.
Article in Environmental science and pollution research international, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 21 citations in OpenAlex.
- Macrophage-derived cathepsin B disrupts intestinal tight junctions through occludin degradation and promotes alcohol-associated liver disease.Journal of hepatology · 2026Article
- Mechanistic insights and ameliorative strategies: advances in DEHP-induced metabolic toxicity and intervention by natural bioactive compounds and probiotics.Lipids in health and disease · 2026Review
- Targeting Cathepsin B-mediated pyroptosis in fibroblasts alleviate ultraviolet-induced skin inflammation and injury.Cell communication and signaling : CCS · 2025Article
- Environmental pollutant Di-(2-ethylhexyl) phthalate induces asthenozoospermia: new insights from network toxicology.Molecular diversity · 2025Article
- Review
- Endocrine disruptors in plastics alter β-cell physiology and increase the risk of diabetes mellitus.American journal of physiology. Endocrinology and metabolism · 2023Review
- β Cell and Autophagy: What Do We Know?Biomolecules · 2023Review
- The Role of Cathepsin B in Pathophysiologies of Non-tumor and Tumor tissues: A Systematic Review.Journal of Cancer · 2023Review
- Cathepsin B deteriorates diabetic cardiomyopathy induced by streptozotocin via promoting NLRP3-mediated pyroptosis.Molecular therapy. Nucleic acids · 2022Article
- Role of adiponectin in osteoarthritis.Frontiers in cell and developmental biology · 2022Review
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Mono-(2-ethylhexyl) phthalate (MEHP) is a primary metabolite of di-(2-ethyl hexyl) phthalate (DEHP) in the organism, which is a major component of plasticizers used worldwide. Exposure to DEHP causes pancreatic beta-cell (INS-1 cells) dysfunction, which is associated with insulin resistance and type 2 diabetes. The present study shows that MEHP decreases the cell viability of INS-1 cells in a concentration-dependent manner and induces pyroptosis at 400 μM. Furthermore, the 400 μM MEHP causes increased lysosomal membrane permeability and cathepsin B (CTSB) release, resulting in NLRP3 activation and pyroptosis. Additionally, low concentration of MEHP (50-200 μM) induces upregulation of autophagy, while 400 μM MEHP reduces autophagy level in INS-1 cells via altering mTORC1 phosphorylation. Surprisingly, CTSB contributes to mTORC1 activation in INS-1 cells treated with 400 μM MEHP. Furthermore, autophagy can alleviate inflammatory response by reducing CTSB activation in MEHP-treated INS-1 cells. These results indicate that exposure to MEHP induces pyroptosis and upregulates autophagy levels in a CTSB-dependent manner, and autophagy plays an essential role in pyroptosis onset in INS-1 cells. Our findings provide a new perspective of the connection between CTSB and autophagy.
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