ArticleMolecular and cellular biology2015
Gossypol Acetic Acid Prevents Oxidative Stress-Induced Retinal Pigment Epithelial Necrosis by Regulating the FoxO3/Sestrin2 Pathway.
Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 38 citations in OpenAlex.
- Targeting LRPPRC to improve corneal wound healing via augmenting autophagy and suppressing TGF-β/Smad signaling post-alkali burn.Journal of translational medicine · 2026Article
- Eugenol alleviates renal ischemia-reperfusion injury induced-endoplasmic reticulum stress via activating Sestrin2.Clinics (Sao Paulo, Brazil) · 2025Article
- Gossypol Acetic Acid Alleviates the Ferroptosis of Chondrocytes in Osteoarthritis by Inhibiting GPX4 Methylation.Current medicinal chemistry · 2025Article
- Sestrin2 serves as a scaffold protein to maintain cardiac energy and metabolic homeostasis during pathological stress.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Review
- Research advances on molecular mechanism and natural product therapy of iron metabolism in heart failure.European journal of medical research · 2024Review
- The potential roles of gossypol as anticancer agent: advances and future directions.Chinese medicine · 2023Review
- A traditional gynecological medicine inhibits ovarian cancer progression and eliminates cancer stem cells via the LRPPRC-OXPHOS axis.Journal of translational medicine · 2023Article
- Sestrin2: multifaceted functions, molecular basis, and its implications in liver diseases.Cell death & disease · 2023Review
- Sestrin2 in diabetes and diabetic complications.Frontiers in endocrinology · 2023Review
- Oxidative stress and mitochondrial transfer: A new dimension towards ocular diseases.Genes & diseases · 2022Review
- Profiling the chemical nature of anti-oxytotic/ferroptotic compounds with phenotypic screening.Free radical biology & medicine · 2021Article
- Gossypol Acetic Acid Attenuates Cardiac Ischemia/Reperfusion Injury in Rats via an Antiferroptotic Mechanism.Biomolecules · 2021Article
- A trifunctional contraceptive gel enhances the safety and quality of sexual intercourse.Bioactive materials · 2021Article
- Target Sestrin2 to Rescue the Damaged Organ: Mechanistic Insight into Its Function.Oxidative medicine and cellular longevity · 2021Review
- Sestrins: Darkhorse in the regulation of mitochondrial health and metabolism.Molecular biology reports · 2020Review
- Enhanced Neuronal Survival and Neurite Outgrowth Triggered by Novel Small Organic Compounds Mimicking the LewisX Glycan.Molecular neurobiology · 2018Article
- Subretinal delivery of erythropoietin alleviates the N-methyl-N-nitrosourea-induced photoreceptor degeneration and visual functional impairments: an in vivo and ex vivo study.Drug delivery · 2017Article
- Retinal pigment epithelial cell necroptosis in response to sodium iodate.Cell death discovery · 2016Article
- 4-Acetoxyphenol Prevents RPE Oxidative Stress-Induced Necrosis by Functioning as an NRF2 Stabilizer.Investigative ophthalmology & visual science · 2015Article
- Sestrin 2 protects human lens epithelial cells from oxidative stress and apoptosis induced by hydrogen peroxide by regulating the mTOR/Nrf2 pathway.International journal of immunopathology and pharmacologyArticle
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The late stage of dry age-related macular degeneration (AMD), or geographic atrophy (GA), is characterized by extensive retinal pigment epithelial (RPE) cell death, and a cure is not available currently. We have recently demonstrated that RPE cells die from necrosis in response to oxidative stress, providing a potential novel mechanism for RPE death in AMD. In this study, we screened U.S. Food and Drug Administration-approved natural compounds and identified gossypol acetic acid (GAA) as a potent inhibitor of oxidative stress-induced RPE cell death. GAA induces antioxidative response and inhibits accumulation of excessive reactive oxygen species in cells, through which it prevents the activation of intrinsic necrotic pathway in response to oxidative stress. Sestrin2 (SESN2) is found to mediate GAA function in antioxidative response and RPE survival upon oxidative stress. Moreover, Forkhead box O3 transcription factor (FoxO3) is further found to be required for GAA-mediated SESN2 expression and RPE survival. Mechanistically, GAA promotes FoxO3 nuclear translocation and binding to the SESN2 enhancer, which in turn increases its transcriptional activity. Taken together, we have identified GAA as a potent inhibitor of oxidative stress-induced RPE necrosis by regulating the FoxO3/SESN2 pathway. This study may have significant implications in the therapeutics of age-related diseases, especially GA.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.