Autophagy
·
2025
·
IF 14.3
Chenyu Luo,Haisheng Liang,Mintao Ji,Caiyong Ye,Yiping Lin,Yuhan Guo,Zhisen Zhang,Yinyin Shu,Xiaoni Jin,Shuangshuang Lu,Wanling Lu,Yazheng Dang,Hong Zhang,Bingyan Li,Guangming Zhou,Zengli Zhang,Lei Chang
Ferroptosis is an iron-dependent regulated form of cell death implicated in various diseases, including cancers, with its progression influenced by iron-dependent peroxidation of phospholipids and dysregulation of the redox system. Whereas the extracellular matrix of tumors provides mechanical cues influencing tumor initiation and progression, its impact on ferroptosis and its mechanisms remains largely unexplored. In this study, we reveal that heightened mechanical tension sensitizes cells to ferroptosis, whereas decreased mechanics confers resistance. Mechanistically, reduced mechanical tension reduces intracellular free iron levels by enhancing FTH1 protein expression. Additionally, low mechanics significantly diminishes NCOA4, pivotal in mediating FTH1 phase separation-induced ferritinophagy. Targeting NCOA4 effectively rescues ferroptosis susceptibility under low mechanical tension through modulation of FTH1 phase separation-driven autophagy. In conclusion, our findings demonstrate that mechanics regulates iron metabolism via NCOA4-FTH1 phase separation-mediated autophagy, thereby influencing ferroptosis sensitivity and offering promising therapeutic avenues for future exploration.
研究领域:
癌症生物学
·
细胞代谢
·
力学生物学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Ovarian Research
·
2024
·Vol. 17
·期 1
·1-17
·
IF 3.8
Sui Xue,Gao Bingqing,Zhang Liu,Wang Yanmin,Ma Junnan,Wu Xingchen,Zhou Chenyu,Liu Min,Zhang Lin
Background Cisplatin (DDP) is one of the most effective anticancer drugs, commonly used to treat advanced ovarian cancer (OC). However, DDP has significant limitations of platinum-based drugs, including chemical resistance and high-dose toxic side effects. Traditional Chinese medicines (TCMs) often presented in the form of formula, in which the herb pair was the basic unit. Scutellaria barbata D.Don and Hedyotis diffusa Willd (SB-HD) are famous TCMs herb pair that have been shown to help treat multiple types of cancers. However, the synergistic effects and mechanism of combination of SB-HD and DDP to enhance DDP chemosensitivity in OC are still unknown.Results In vitro, we found that the optimal proportion of SB-HD to inhibit the proliferation of OC cells was 2:1, SB-HD and DDP were shown to synergistically reduce the viability of OC cells, inhibit the colony formation, promote cell cycle arrest and apoptosis, as well as inhibit cell migration and invasion. In vivo, combination treatment significantly inhibited the growth of subcutaneous tumors in BALB/c nude mice and reduced the toxic side effects of DDP. Mechanistically, SB-HD and DDP combination treatment significantly promoted oxidative stress response, decreased MMP, inhibited ATP production, decreased ROS levels and increased SOD activity, increased the expression of NRF2, HO-1, ATG5 and LC3, decreased the expression of p62 and FTH1 both in OC cells and tumor tissue of mice. Inhibitor 3-MA (Methyladenine, autophagy inhibitor) and Fer-1 (Ferrostatin-1, iron ion inhibitor) can effectively reverse the expression changes of the key target proteins, but not ZnPP (Zinc protoporphyrin, HO-1 inhibitor). Through bioinformatics analysis, it was found that the abnormal expression level of NRF2 and FTH1 mRNA has a high prognostic value, at the same time, the other four key proteins respectively or interacting with NRF2 and FTH1, also play important roles in the occurrence and development of OC.Conclusion Our findings uncover a synergistic effect of SB-HD and DDP against OC through modulating oxidative stress via NRF2-FTH1 autophagic degradation pathway, which may provide an important theoretical foundation for the use of SB-HD and a new strategy for enhancing DDP chemosensitivity as well as reducing toxic side effects.
研究领域:
肿瘤学
·
药理学
·
传统中药学
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产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2023
·
IF 4.3
Kaiyuan Chen,Yahui Tang,Linhua Lan,Mengxuan Li,Zhongqiu Lu
Acute kidney injury (AKI) induced by diquat (DQ) progresses rapidly, leading to high mortality, and there is no specific antidote for this chemical. Our limited knowledge of the pathogenic toxicological mechanisms of DQ has hindered the development of treatments against DQ poisoning. Pyroptosis is a form of programmed cell death and was recently identified as a novel molecular mechanism of drug-induced AKI. To explore the role of pyroptosis in HK-2 cells exposed to DQ, the plasma membrane damage of the cells was detected by LDH release assay. Western blot was performed to detect the cleavage of GSDME. Proteomics analysis was performed to explore the mechanism of DQ induced nephrotoxicity . FerroOrange probe was used to measure the intracellular Fe 2+ levels. Herein, we show that DQ induces pyroptosis in HK-2 cells. Mechanistically, DQ induces the accumulation of mitochondrial ROS and initiates the cleavage of gasdermin E (GSDME) in an intrinsic mitochondrial pathway. Knockout of GSDME attenuated DQ-induced cell death. Further analysis revealed that loss of FTH1 induces Fe 2+ accumulation, contributing to DQ-induced pyroptosis. Knockdown LC3B could help restore the expression of FTH1 and improve cell viability . Moreover, we found DFO , an iron chelator , could reduce cellular Fe 2+ levels and inhibit pyroptosis. Collectively, these findings suggest an unrecognized mechanism for GSDME-dependent pyroptosis in DQ-induced AKI.
研究领域:
毒理学
·
细胞生物学
·
肾脏病学
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产品关联
DOI
PubMed
高影响因子
Pharmaceuticals
·
2022
·Vol. 15
·期 10
·1177
·
IF 5.215
Yini Dang,Qing He,Siyu Yang,Huaiqing Sun,Yin Liu,Wanting Li,Yi Tang,Yu Zheng,Ting Wu
Objectives: Despite significant advances in neuroscience, the mechanisms of AD are not fully understood. Single-cell RNA sequencing (scRNA-seq) techniques provide potential solutions to analyze cellular composition of complex brain tissue and explore cellular and molecular biological mechanisms of AD. Methods: We investigated cellular heterogeneity in AD via utilization of bioinformatic analysis of scRNA-seq in AD patients and healthy controls from the Gene Expression Omnibus (GEO) database. The “GOplot” package was applied to explore possible biological processes in oligodendrocytes, astrocytes, and oligodendrocyte progenitor cells (OPCs). Expression patterns and biological functions of differentially expressed genes (DEGs) from scRNA-seq data were validated in RNA sequencing data. DEGs in astrocytes interacted with ferroptosis-related genes in FerrDb. CCK-8 and EdU assays were performed to measure cell proliferation ability. ROS, Fe2+level, mitochondrial membrane potentials, iron concentrations, and total iron binding capacity (TIBC) in serum were evaluated. Y-maze and elevated maze were used to measure anxiety-like behavior. Autonomous and exploration behaviors or learning and memory ability in mice were analyzed using open field test and novel object recognition test. Results: Multiple clusters were identified, including oligodendrocytes, astrocytes, OPCs, neurons, microglia, doublets, and endothelial cells. Astrocytes were significantly decreased in AD, while oligodendrocytes and OPCs increased. Cell-to-cell ligand–receptor interaction analysis revealed that astrocytes, neurons, and OPCs mainly established contacts with other cells via the NRG3–ERBB4 ligand–receptor pair. GO and KEGG analyses found that astrocytes were enriched in the ferroptosis pathway. FTH1 and SAT1 in astrocytes were identified as hub mRNAs associated with ferroptosis. Serum iron concentration of 5xFAD mice was higher than that of WT, and emotional and cognitive function were significantly impaired as compared to WT. Serum iron concentration was negatively correlated with number of astrocytes and percentage of time spent entering the novelty arm in the Y-maze test, while it was positively correlated with percentage of time spent in the central area. Meanwhile, number of astrocytes was negatively correlated with percentage of time spent in the central area, while it was positively correlated with percentage of time spent entering the novelty arm. Conclusions: Through scRNA-seq analysis, we found that ferroptosis was activated in astrocytes and may contribute to the pathophysiological process in the entorhinal cortex. FTH1 and SAT1 were identified to impact astrocyte ferroptosis. Emotional and cognitive impairment in AD was associated with astrocyte ferroptosis. Our findings provide clues to reveal the pathophysiological processes following AD at the cellular level and highlight potential drug targets for the treatment of AD.Keywords:Alzheimer’s disease;single-cell RNA sequencing;astrocytes;ferroptosis
研究领域:
神经科学
·
分子生物学
·
生物信息学
·
神经退行性疾病
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DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Jingxuan Cui,Yujia Chen,Qiannan Yang,Peng Zhao,Mian Yang,Xiaoqi Wang,Ge Mang,Xiangyu Yan,Di Wang,Zhonghua Tong,Penghe Wang,Yingjin Kong,Naixin Wang,Dongni Wang,Nana Dong,Mingyang Liu,Mingyan E,Maomao Zhang,Bo Yu
Doxorubicin (DOX) is an effective anticancer agent, but its clinical utility is constrained by dose-dependent cardiotoxicity, partly due to cardiomyocyte ferroptosis. However, the progress of developing cardioprotective medications to counteract ferroptosis has encountered obstacles. Protosappanin A (PrA), an anti-inflammatory compound derived from hematoxylin, shows potential against DOX-induced cardiomyopathy (DIC). Here, it is reported that PrA alleviates myocardial damage and dysfunction by reducing DOX-induced ferroptosis and maintaining mitochondrial homeostasis. Subsequently, the molecular target of PrA through proteome microarray, molecular docking, and dynamics simulation is identified. Mechanistically, PrA physically binds with ferroptosis-related proteins acyl-CoA synthetase long-chain family member 4 (ACSL4) and ferritin heavy chain 1 (FTH1), ultimately inhibiting ACSL4 phosphorylation and subsequent phospholipid peroxidation, while also preventing FTH1 autophagic degradation and subsequent release of ferrous ions (Fe 2+ ) release. Given the critical role of ferroptosis in the pathogenesis of ischemia-reperfusion (IR) injury, this further investigation posits that PrA can confer a protective effect against IR-induced cardiac damage by inhibiting ferroptosis. Overall, a novel pharmacological inhibitor is unveiled that targets ferroptosis and uncover a dual-regulated mechanism for cardiomyocyte ferroptosis in DIC, highlighting additional therapeutic options for chemodrug-induced cardiotoxicity and ferroptosis-triggered disorders.
研究领域:
药理学
·
心脏病学
·
肿瘤学
·
分子生物学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2025
·
IF 4.5
Ying Chen,Qin Ma,Jun Zhang,Jianhang Li,Yu’e Wang,Yongchao Yao,Yang Ding,Xin Dai,Xinghong Luo,Linjing Wu,Ling Tao,Xiangchun Shen
Due to the increased expression of iron storage proteins in cancer cells, utilizing the endogenous iron-catalyzed Fenton reaction for cancer ferroptosis therapy has recently emerged as a prominent research focus. However, endogenous iron primarily exists within ferroxidase FTH1 in the Fe (III)-bound state, hindering the effective catalysis of the Fenton reaction. Herein, an endogenous iron(II) self-enriched Fenton nanocatalyst (BAI@cLANCs) is fabricated by encapsulating the FTH1 inhibitor baicalin (BAI) in cross-linked lipoic acid nanocarriers (cLANCs) to amplify endogenous ferroptosis. Once internalized, BAI@cLANCs are disrupted by glutathione (GSH) in tumor cells to release BAI, which inhibits FTH1 activity and hinders Fe2+ oxidation. Meanwhile, cLANCs degrade into dihydrolipoic acid (DHLA), which reduces Fe3+ to Fe2+, synergically enriching endogenous Fe2+. Simultaneously, both BAI and DHLA stimulate H2O2 production and facilitate the Fenton reaction to produce abundant ·OH, thereby triggering lipid peroxidation and inducing tumor ferroptosis. Moreover, the reduction of Fe3+ to Fe2+ depletes GSH, facilitating ·OH production and inactivating glutathione peroxidase-4, ultimately amplifying tumor ferroptosis. Overall, this work highlights the potential of an endogenous iron(II) self-enriched Fenton nanocatalyst for cancer ferroptosis therapy, providing a paradigm for amplifying endogenous ferroptosis by inhibiting FTH1 activity and reducing iron(III) to enrich endogenous iron(II).
研究领域:
癌症治疗
·
纳米技术
·
生物化学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2026
·
IF 6.1
Dong Fan,Zongming Wang,Shixue Luo,Xuanhao Huang,Xingyi Yuan,Yanan Wang,Zhongyu Wang,Huitong Chen,Weiwen Wang,Yuxin Ma,Chang Zhou,Xiaobao Jin,Jing Liu,Xin Wang
Background: Nonfunctioning pituitary adenoma (NFPA) is among the most prevalent intracranial tumors. As surgical resection remains the primary treatment, there is a need for new therapeutic strategies. Plumbagin (PLB), a bioactive naphthoquinone compound derived from the roots of Plumbaginaceae Juss, has been used in anti-tumor research in recent years, but its mechanism remains controversial.Purpose: The aim of this study was to explore the molecular mechanism of PLB-induced ferroptosis in NFPA.Methods: The cell viability of PLB against PDFS cells was first assessed by CCK-8, colony formation, and EDU assays. Network pharmacology, molecular docking, and molecular dynamics were then used to screen out targets associated with ferroptosis. Finally, the Nrf2/FTH1 pathway was validated by a 3D multicellular tumour spheroids (MCTSs) model, q-PCR, and Western blot in vitro and in vivo.Results: Compared to temozolomide (TMZ), PLB more potently inhibited the viability of PDFS cells. In vitro, PLB treatment was associated with downregulation of the Nrf2/FTH1 pathway, accompanied by increased lipid peroxidation and labile iron pool (LIP) accumulation. Furthermore, PLB treatment led to the upregulation of NCOA4 and an increase in intracellular free iron, consistent with ferritinophagy activation. These effects collectively point to the induction of ferroptosis.Conclusion: This study demonstrates that PLB may induce ferroptosis in PDFS cells. The mechanism involves suppression of the Nrf2/FTH1 pathway, subsequent upregulation of NCOA4, and ferritinophagy-driven iron overload. These results identify PLB as a potential ferroptosis inducer and warrant further investigation into its therapeutic potential for NFPA. The image shows a biochemical pathway illustrating ferritinophagy and ferroptosis. Iron in the form of Fe superscript 3 is transported by transferrin into the cell, where it is stored in ferritin. Ferritin is directed to the autolysosome, facilitated by Lamp2, where iron is released as Fe superscript 2. NCOA4 and LC3 are involved in ferritinophagy, leading to the labile iron pool. The Fenton reaction produces reactive oxygen species, contributing to ferroptosis. Nrf2 regulates FTH1, with arrows indicating promotion and inhibition. Plumbagin is shown affecting the pathway, with an illustration of a mouse receiving an injection, highlighting the interaction between NCOA4, FTH1 and Nrf2 in the brain. Arrows indicate promotion and inhibition effects within the pathway.Diagram of ferritinophagy and ferroptosis: iron regulation, NCOA4, FTH1, Nrf2 and plumbagin effects.
✓ 已验证
DOI
PubMed
高影响因子
Food & Function
·
2021
·Vol. 12
·期 24
·12671-12682
·
IF 5.396
Jing-yi Ren,Bo-wen Yin,Xiang Li,Si-qi Zhu,Jin-liang Deng,Yi-ting Sun,Zhen-ao Zhang,Zi-hao Guo,Huan-ting Pei,Fan Zhang,Rui-qiang Li,Feng-ge Chen,Yu-xia Ma
Objective: This study aimed to elucidate the pharmacological effects of sesamin (Ses) and its mechanism of action towards PM2.5-induced cardiovascular injuries. Method: Forty Sprague Dawley (SD) rats were randomly divided into five groups: a saline control group; a PM2.5 exposure group; and low-, middle-, and high-dose Ses pretreatment groups. The SD rats were pretreated with different concentrations of Ses for 21 days. Afterward, the rats were exposed to ambient PM2.5 by intratracheal instillation every other day for a total of three times. The levels of inflammatory markers, including tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and interleukin-6 (IL-6), and indicators related to oxidative responses, such as total superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA), were measured in the blood and heart. The expression of ferroptosis-related proteins in heart tissues was determined via western blot and immunohistochemistry. Results: Ses pretreatment substantially ameliorated cardiovascular injuries in rats as evidenced by the decrease in the pathological score and collagen area. The decreased levels of SOD, GSH, and GSH-Px in the heart and serum were inhibited by Ses. In addition, Ses not only notably increased the activity of antioxidant enzymes but also reduced the levels of MDA, CK, LDH, CK-MB, IL-6, TNF-α, IL-1β, and IL-6. Furthermore, Ses pretreatment upregulated the expression levels of GPX4, SLC7A11, TFRC, and FPN1 and inhibited the expression levels of FTH1 and FTL. Conclusion: Ses pretreatment could ameliorate PM2.5-induced cardiovascular injuries perhaps by inhibiting ferroptosis. Therefore, Ses pretreatment may be a novel strategy for the prevention and treatment of PM2.5-induced cardiovascular injury.
研究领域:
药理学
·
心脏病学
·
毒理学
·
环境健康
✓ 已验证
DOI
PubMed
高影响因子
DIGESTIVE DISEASES AND SCIENCES
·
2023
·
IF 3.1
Tian Xiaorong,Wang Yuxin,Yuan Mengshu,Zheng Weiping,Zuo Huaiwen,Zhang Xinru,Song Hongli
Background Ischemia–reperfusion injury (IRI) is an important cause of graft dysfunction post-liver transplantation, where donor liver with severe steatosis is more sensitive to IRI. Liver IRI involves ferroptosis and can be alleviated by heme oxygenase-1-modified bone marrow mesenchymal stem cells (HO-1/BMMSCs). Aims To explore the role and mechanism of HO-1/BMMSCs in severe steatotic liver IRI. Methods A severe steatotic liver IRI rat model and a hypoxia/reoxygenation (H/R) of severe steatosis hepatocyte model were established. Liver and hepatocyte damage was evaluated via liver histopathology and cell activity. Ferroptosis was evaluated through ferroptosis indexes. Nuclear factor erythroid 2-related factor 2 (Nrf2) was knocked down in severe steatotic hepatocytes. The role of Nrf2 and AMPK in HO-1/BMMSC inhibition of ferroptosis was examined using the AMP-activated protein kinase (AMPK) pathway inhibitor Compound C. Results The HO-1/BMMSCs alleviated severe steatotic liver IRI and ferroptosis. HO-1/BMMSCs promoted ferritin heavy chain 1(FTH1), Nrf2, and phosphorylated (p)-AMPK expression in the H/R severe steatotic hepatocytes. Nrf2 knockdown decreased FTH1 expression levels but did not significantly affect p-AMPK expression levels. The protective effect of HO-1/BMMSCs against H/R injury in severe steatotic hepatocytes and the inhibitory effect on ferroptosis were reduced. Compound C decreased p-AMPK, Nrf2, and FTH1 expression levels, weakened the HO-1/BMMSC protective effect against severe steatotic liver IRI and H/R-injured severe steatotic hepatocytes, and reduced the inhibition of ferroptosis. Conclusions Ferroptosis was involved in HO-1/BMMSC reduction of severe steatotic liver IRI. HO-1/BMMSCs protected against severe steatotic liver IRI by inhibiting ferroptosis through the AMPK–Nrf2–FTH1 pathway. Graphical Abstract HO-1/BMMSCs activate AMPK, which activates Nrf2, promotes its nuclear transcription, then promotes the expression of its downstream protein FTH1, thereby inhibiting ferroptosis and attenuating severe steatotic liver IRI in rats. Glu: glutamic acid; Cys: cystine; GSH: glutathione; GPX4: glutathione peroxidase 4; HO-1/BMMSCs: HO-1-modified BMMSCs; Fer-1: ferrostatin-1; DFO: deferoxamine; FTH1: ferritin heavy chain1; p-AMPK: phosphorylated AMP-activated protein kinase; Nrf2: nuclear factor erythroid 2-related factor 2; IRI: ischemia-reperfusion injury; MCD: methionine-choline deficiency
研究领域:
移植学
·
肝病学
·
干细胞生物学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Tongwen Huang,Ke Zhang,Junqiao Wang,Kaihong He,Xingtao Zhou,Shaoping Nie
Acrylamide (ACR) generated in carbohydrate-rich foods during thermal processing has been demonstrated to exhibit hepatotoxicity. As one of the most consumed flavonoids with diet, quercetin (QCT) possesses the ability to protect against ACR-induced toxicity, albeit its mechanism is unclear. Herein, we discovered that QCT alleviated ACR-induced elevated levels of reactive oxygen species (ROS), AST, and ALT in mice. RNA-seq analysis revealed that QCT reversed the ferroptosis signaling pathway upregulated by ACR. Subsequently, experiments indicated that QCT inhibited ACR-induced ferroptosis through the reduction of oxidative stress. With autophagy inhibitor chloroquine, we further confirmed that QCT suppressed ACR-induced ferroptosis by inhibiting oxidative stress-driven autophagy. Additionally, QCT specifically reacted with autophagic cargo receptor NCOA4, blocked the degradation of iron storage protein FTH1, and eventually downregulated the intracellular iron levels and the consequent ferroptosis. Collectively, our results presented a unique approach to alleviate ACR-induced liver injury by targeting ferroptosis with QCT.
研究领域:
毒理学
·
药理学
·
分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
FASEB JOURNAL
·
2022
·Vol. 36
·期 12
·e22665
·
IF 5.834
Yang Zheng,Tiejian Zhao,Jiaru Wang,Ruizhu Jiang,Jinbiao Huang,Weimin Li,Jiahui Wang
To explore the effect of curcumol on autophagy and ferroptosis of hepatic stellate cells, and to clarify the molecular mechanism of its anti-hepatic fibrosis. In the present study, we report that curcumol promotes the death of activated HSCs and reduces the deposition of extracellular matrix. Interestingly, curcumol treatment can trigger ferroptosis to eliminate activated HSCs characterized by iron overload, lipid ROS accumulation, glutathione depletion, and lipid peroxidation. Curcumol promotes HSC autophagy, which may be the key mechanism for its induction of ferroptosis. It is worth noting that the upregulation of nuclear receptor coactivator 4 (NCOA4) may play a key molecular mechanism. NCOA4 mediates the release of iron ions and induces the occurrence of ferroptosis. Overall, curcumol promotes autophagy in hepatic stellate cells, mediates the degradation of NCOA4 and FTH1 complexes, releases iron ions, leads to iron overload, and induces ferroptosis, which may be an important mechanism for its anti-hepatic fibrosis effect.
研究领域:
药理学
·
细胞生物学
·
分子生物学
·
肝病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
·
2026
·
IF 4.3
Leilei Qin,Yanli Guo,Yi Zhang,Nianting Tong,Chunning Zhao
Ribosomal L1 domain-containing protein 1 (RSL1D1) is an RNA-binding protein that relates to senescence. Nevertheless, the mechanism of RSL1D1 in modulating senescence and ferroptosis in diabetic retinopathy (DR) remains undefined. The DR mice were developed by intraperitoneal injection of STZ, and AAV targeting RPE was used for gene intervention. ARPE-19 cells were infected using oe-RSL1D1 and sh-FTH1 lentivirus before 30 mM high glucose (HG) exposure. Cell damage was assessed by measuring the expression of senescence and ferroptosis markers in ARPE-19 cells, along with oxidative stress indicators and Fe 2+ levels. RSL1D1 and FTH1 expression were significantly reduced in the retinal pigment epithelium (RPE) layer of diabetic mice and HG-induced ARPE-19 cells. Downregulation of RSL1D1 led to RPE cell senescence and dysregulated iron homeostasis-induced ferroptosis. HG treatment reduced the interaction between RSL1D1 protein and FTH1 mRNA in ARPE-19 cells, while RSL1D1 overexpression enhanced this interaction, thereby stabilizing FTH1 mRNA expression. The alleviating effects of RSL1D1 overexpression on retinal pigment epithelium cell senescence and ferroptosis in vitro and in vivo were compromised by FTH1 knockdown. Overall, this study unveils a posttranscriptional regulation of FTH1 by RSL1D1 and uncovers the implication of RSL1D1/FTH1 in cellular senescence and ferroptosis in DR.
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产品关联
DOI
PubMed
高影响因子
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