Redox Biology最新文献

{"title":"Oxidative stress promotes oral carcinogenesis via Thbs1-mediated M1-like tumor-associated macrophages polarization","authors":"","doi":"10.1016/j.redox.2024.103335","DOIUrl":"10.1016/j.redox.2024.103335","url":null,"abstract":"<div><p>Although oxidative stress is closely associated with tumor invasion and metastasis, its’ exact role and mechanism in the initial stage of oral cancer remain ambiguous. Glutamine uptake mediated by alanine-serine-cysteine transporter 2 (ASCT2) participates in glutathione synthesis to resolve oxidative stress. Currently, we firstly found that ASCT2 deletion caused oxidative stress in oral mucosa and promoted oral carcinogenesis induced by 4-Nitroquinoline-1-oxide (4-NQO) using transgenic mice of ASCT2 knockout in oral epithelium. Subsequently, we identified an upregulated gene Thbs1 linked to macrophage infiltration by mRNA sequencing and immunohistochemistry. Importantly, multiplex immunohistochemistry showed M1-like tumor-associated macrophages (TAMs) were enriched in cancerous area. Mechanically, targeted ASCT2 effectively curbed glutamine uptake and caused intracellular reactive oxygen species (ROS) accumulation, which upregulated Thbs1 in oral keratinocytes and then activated p38, Akt and SAPK/JNK signaling to polarize M1-like TAMs via exosome-transferred pathway. Moreover, we demonstrated M1-like TAMs promoted malignant progression of oral squamous cell carcinoma (OSCC) both in <em>vitro</em> and in <em>vivo</em> by a DOK transformed cell line induced by 4-NQO. All these results establish that oxidative stress triggered by ASCT2 deletion promotes oral carcinogenesis through Thbs1-mediated M1 polarization, and indicate that restore redox homeostasis is a new approach to prevent malignant progression of oral potentially malignant disorders.</p></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213231724003136/pdfft?md5=5dc2129c56e2ce8d0bd36ebe22e43356&pid=1-s2.0-S2213231724003136-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142158480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipocalin-2 aggravates blood-brain barrier dysfunction after intravenous thrombolysis by promoting endothelial cell ferroptosis via regulating the HMGB1/Nrf2/HO-1 pathway","authors":"","doi":"10.1016/j.redox.2024.103342","DOIUrl":"10.1016/j.redox.2024.103342","url":null,"abstract":"<div><h3>Background</h3><p>Disruption of the blood-brain barrier (BBB) is a major contributor to hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS) following intravenous thrombolysis (IVT). However, the clinical therapies aimed at BBB protection after IVT remain limited.</p></div><div><h3>Methods</h3><p>One hundred patients with AIS who underwent IVT were enrolled (42 with HT and 58 without HT 24 h after IVT). Based on the cytokine chip, the serum levels of several AIS-related proteins, including LCN2, ferritin, matrix metalloproteinase-3, vascular endothelial-derived growth factor, and X-linked inhibitor of apoptosis, were detected upon admission, and their associations with HT were analyzed. After finding that LCN2 was related to HT in patients with IVT, we clarified whether the modulation of LCN2 influenced BBB dysfunction and HT after thrombolysis and investigated the potential mechanism.</p></div><div><h3>Results</h3><p>In patients with AIS following IVT, logistic regression analysis showed that baseline serum LCN2 (<em>p</em> = 0.023) and ferritin (<em>p</em> = 0.046) levels were independently associated with HT. A positive correlation between serum LCN2 and ferritin levels was identified in patients with HT. In experimental studies, recombinant LCN2 (rLCN2) significantly aggravated BBB dysfunction and HT in the thromboembolic stroke rats after thrombolysis, whereas LCN2 inhibition by ZINC006440089 exerted opposite effects. Further mechanistic studies showed that, LCN2 promoted endothelial cell ferroptosis, accompanied by the induction of high mobility group box 1 (HMGB1) and the inhibition of nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins. Ferroptosis inhibitor ferrostatin-1 (fer-1) significantly restricted the LCN2-mediated BBB disruption. Transfection of LCN2 and HMGB1 siRNA inhibited the endothelial cell ferroptosis, and this effects was reversed by Nrf2 siRNA.</p></div><div><h3>Conclusion</h3><p>LCN2 aggravated BBB disruption after thrombolysis by promoting endothelial cell ferroptosis via regulating the HMGB1/Nrf2/HO-1 pathway, this may provide a promising therapeutic target for the prevention of HT after IVT.</p></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213231724003203/pdfft?md5=c5ed40abbe10d315e6e07e5cbfdccb8a&pid=1-s2.0-S2213231724003203-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142163126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the ferroptosis pathways in dorsal root ganglia of Friedreich ataxia models. The role of LKB1/AMPK, KEAP1, and GSK3β in the impairment of the NRF2 response","authors":"","doi":"10.1016/j.redox.2024.103339","DOIUrl":"10.1016/j.redox.2024.103339","url":null,"abstract":"<div><p>Friedreich ataxia (FA) is a rare neurodegenerative disease caused by decreased levels of the mitochondrial protein frataxin. Frataxin has been related in iron homeostasis, energy metabolism, and oxidative stress. Ferroptosis has recently been shown to be involved in FA cellular degeneration; however, its role in dorsal root ganglion (DRG) sensory neurons, the cells that are affected the most and the earliest, is mostly unknown. In this study, we used primary cultures of frataxin-deficient DRG neurons as well as DRG from the FXN^I151F mouse model to study ferroptosis and its regulatory pathways. A lack of frataxin induced upregulation of transferrin receptor 1 and decreased ferritin and mitochondrial iron accumulation, a source of oxidative stress. However, there was impaired activation of NRF2, a key transcription factor involved in the antioxidant response pathway. Decreased total and nuclear NRF2 explains the downregulation of both SLC7A11 (a member of the system Xc, which transports cystine required for glutathione synthesis) and glutathione peroxidase 4, responsible for increased lipid peroxidation, the main markers of ferroptosis. Such dysregulation could be due to the increase in KEAP1 and the activation of GSK3β, which promote cytosolic localization and degradation of NRF2. Moreover, there was a deficiency in the LKB1/AMPK pathway, which would also impair NRF2 activity. AMPK acts as a positive regulator of NRF2 and it is activated by the upstream kinase LKB1. The levels of LKB1 were reduced when frataxin decreased, in agreement with reduced pAMPK (Thr172), the active form of AMPK. SIRT1, a known activator of LKB1, was also reduced when frataxin decreased. MT-6378, an AMPK activator, restored NRF2 levels, increased GPX4 levels and reduced lipid peroxidation. In conclusion, this study demonstrated that frataxin deficiency in DRG neurons disrupts iron homeostasis and the intricate regulation of molecular pathways affecting NRF2 activation and the cellular response to oxidative stress, leading to ferroptosis.</p></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213231724003173/pdfft?md5=85156d203fb368053c5061c8d47285b5&pid=1-s2.0-S2213231724003173-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142144415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative stress-mediated protein sulfenylation in human diseases: Past, present, and future","authors":"","doi":"10.1016/j.redox.2024.103332","DOIUrl":"10.1016/j.redox.2024.103332","url":null,"abstract":"<div><p>Reactive Oxygen Species (ROS) refer to a variety of derivatives of molecular oxygen that play crucial roles in regulating a wide range of physiological and pathological processes. Excessive ROS levels can cause oxidative stress, leading to cellular damage and even cell demise. However, moderately elevated levels of ROS can mediate the oxidative post-translational modifications (oxPTMs) of redox-sensitive proteins, thereby affecting protein functions and regulating various cellular signaling pathways. Among the oxPTMs, ROS-induced reversible protein sulfenylation represents the initial form of cysteine oxidation for sensing redox signaling. In this review, we will summarize the discovery, chemical formation, and detection approaches of protein sulfenylation. In addition, we will highlight recent findings for the roles of protein sulfenylation in various diseases, including thrombotic disorders, diabetes, cardiovascular diseases, neurodegenerative diseases, and cancer.</p></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213231724003100/pdfft?md5=ef265da7f1a6af6efdc55056522b0cbd&pid=1-s2.0-S2213231724003100-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142096295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of dietary inflammation index and composite dietary antioxidant index with preserved ratio impaired spirometry in US adults and the mediating roles of triglyceride-glucose index: NHANES 2007–2012","authors":"","doi":"10.1016/j.redox.2024.103334","DOIUrl":"10.1016/j.redox.2024.103334","url":null,"abstract":"<div><h3>Background</h3><p>Previous studies have shown that inflammatory and antioxidant dietary patterns can modify the risk of COPD, yet few studies have examined the association of these diets with its early signs (PRISm), and the potential role of metabolic disorders remains to be elucidated.</p></div><div><h3>Methods</h3><p>Data from 9529 individuals who participated in the 2007–2012 National Health and Nutrition Examination Survey (NHANES) were analyzed. The Dietary Inflammation Index (DII) and the Dietary Antioxidant Composite Index (CDAI) were assessed using 24-h dietary recall, multiple metabolic indicators were calculated according to biochemical markers, and lung function parameters defined PRISm cases. Individual and joint effects of DII and CDAI were evaluated by generalized linear models and binary logistic regression models, and mediation effects of metabolic indicators were further explored by causal mediation analysis.</p></div><div><h3>Results</h3><p>Increased DII was associated with decreased lung function (FEV1: β = −18.82, FVC: β = −29.2; OR = 1.04) and increased metabolic indicators (β = 0.316, 0.036, 0.916, 0.033, and 0.145 on MAP, UA, TC, TyG, and MS, respectively). Contrary to this, CDAI were positively and negatively associated with lung function (FEV1: β = 3.42; FVC: β = 4.91; PRISm: OR = 0.99) and metabolic indicators (β &lt; 0), respectively. Joint effects of DII and CDAI indicated the minimal hazard effects of DII on TyG (β = −0.11), FEV1 (β = 72.62), FVC (β = 122.27), and PRISm (OR = 0.79) in subjects with high CDAI when compared with those with low CDAI (low DII + high CDAI vs. high DII + low CDAI). Furthermore, TyG mediated 13.74 %, 8.29 %, and 21.70 % of DII- and 37.30 %, 20.90 %, and 12.32 % of CDAI-FEV1, -FVC, and -PRISm associations, respectively.</p></div><div><h3>Conclusions</h3><p>These findings indicated that CDAI can attenuate the adverse effects of DII on metabolic disorders and lung function decline, which provides new insight for diet modification in preventing early lung dysfunction.</p></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213231724003124/pdfft?md5=718d6c3a36cae5dfcde9a2332fdb56f4&pid=1-s2.0-S2213231724003124-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142096298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liver-secreted FGF21 induces sarcopenia by inhibiting satellite cell myogenesis via klotho beta in decompensated cirrhosis","authors":"","doi":"10.1016/j.redox.2024.103333","DOIUrl":"10.1016/j.redox.2024.103333","url":null,"abstract":"<div><h3>Background &amp; aims</h3><p>Sarcopenia, a prevalent condition, significantly impacts the prognosis of patients with decompensated cirrhosis (DC). Serum fibroblast growth factor 21 (FGF21) levels are significantly higher in DC patients with sarcopenia. Satellite cells (SCs) play a role in aging- and cancer-induced sarcopenia. Here, we investigated the roles of FGF21 and SCs in DC-related sarcopenia as well as the underlying mechanisms.</p></div><div><h3>Methods</h3><p>We developed two DC mouse models and performed in vivo and in vitro experiments. Klotho beta (KLB) knockout mice in SCs were constructed to investigate the role of KLB downstream of FGF21. In addition, biological samples were collected from patients with DC and control patients to validate the results.</p></div><div><h3>Results</h3><p>Muscle wasting and impaired SC myogenesis were observed in the DC mouse model and patients with DC. Elevated circulating levels of liver-derived FGF21 were observed, which were significantly negatively correlated with skeletal muscle mass/skeletal muscle index. Liver-secreted FGF21 induces SC dysfunction, contributing to sarcopenia. Mechanistically, FGF21 in the DC state exhibits enhanced interactions with KLB on SC surfaces, leading to downstream phosphatase and tensin homolog upregulation. This inhibits the protein kinase B (PI3K/Akt) pathway, hampering SC proliferation and differentiation, and blocking new myotube formation to repair atrophy. Neutralizing circulating FGF21 using neutralizing antibodies, knockdown of hepatic FGF21 by adeno-associated virus, or knockout of KLB in SCs effectively improved or reversed DC-related sarcopenia.</p></div><div><h3>Conclusions</h3><p>Hepatocyte-derived FGF21 mediates liver-muscle crosstalk, which impairs muscle regeneration via the inhibition of the PI3K/Akt pathway, thereby demonstrating a novel therapeutic strategy for DC-related sarcopenia.</p></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213231724003112/pdfft?md5=dc6982b977379b43cd22cebf1547c570&pid=1-s2.0-S2213231724003112-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142122245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new paradigm in intracellular immunology: Mitochondria emerging as leading immune organelles","authors":"","doi":"10.1016/j.redox.2024.103331","DOIUrl":"10.1016/j.redox.2024.103331","url":null,"abstract":"<div><p>Mitochondria, traditionally recognized as cellular 'powerhouses' due to their pivotal role in energy production, have emerged as multifunctional organelles at the intersection of bioenergetics, metabolic signaling, and immunity. However, the understanding of their exact contributions to immunity and inflammation is still developing. This review first introduces the innovative concept of intracellular immunity, emphasizing how mitochondria serve as critical immune signaling hubs. They are instrumental in recognizing and responding to pathogen and danger signals, and in modulating immune responses. We also propose mitochondria as the leading immune organelles, drawing parallels with the broader immune system in their functions of antigen presentation, immune regulation, and immune response. Our comprehensive review explores mitochondrial immune signaling pathways, their therapeutic potential in managing inflammation and chronic diseases, and discusses cutting-edge methodologies for mitochondrial research. Targeting a broad readership of both experts in mitochondrial functions and newcomers to the field, this review sets forth new directions that could transform our understanding of intracellular immunity and the integrated immune functions of intracellular organelles.</p></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213231724003094/pdfft?md5=bd9439adcc52307f69f46d7918284e52&pid=1-s2.0-S2213231724003094-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142096294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intermittent ozone inhalation during house dust mite-induced sensitization primes for adverse asthma phenotype","authors":"","doi":"10.1016/j.redox.2024.103330","DOIUrl":"10.1016/j.redox.2024.103330","url":null,"abstract":"<div><p>The ability of air pollution to induce acute exacerbation of asthma is well documented. However, the ability of ozone (O₃), the most reactive gaseous component of air pollution, to function as a modulator during sensitization is not well established. C57BL/6 J male mice were intranasally sensitized to house dust mite (HDM) (40 μg/kg) for 3 weeks on alternate days in parallel with once-a-week O₃ exposure (1 ppm). Mice were euthanized 24 h following the last HDM challenge. Lung lavage, histology, lung function (both forced oscillation and forced expiration-based), immune cell profiling, inflammation (pulmonary and systemic), and immunoglobulin production were assessed. Compared to HDM alone, HDM + O₃ leads to a significant increase in peribronchial inflammation (p &lt; 0.01), perivascular inflammation (p &lt; 0.001) and methacholine-provoked large airway hyperreactivity (p &lt; 0.05). Serum total IgG and IgE and HDM-specific IgG1 were 3–5 times greater in HDM + O₃ co-exposure compared to PBS and O₃-exposed groups. An increase in activated/mature lung total and monocyte-derived dendritic cells (p &lt; 0.05) as well as T-activated, and T memory lymphocyte subset numbers (p &lt; 0.05) were noted in the HDM + O₃ group compared to HDM alone group. Concurrent O₃ inhalation and HDM sensitization also caused significantly greater (p &lt; 0.05) lung tissue interleukin-17 pathway gene expression and mediator levels in the serum. Redox imbalance was manifested by impaired lung antioxidant defense and increased oxidants. O₃ inhalation during allergic sensitization coalesces in generating a significantly worse T_H17 asthmatic phenotype.</p></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213231724003082/pdfft?md5=5faf371eda1b4b43c02be72e2434e148&pid=1-s2.0-S2213231724003082-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142148358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Mitofusin 1 in mediating reactive oxygen species in alveolar macrophages during Streptococcus pneumoniae","authors":"","doi":"10.1016/j.redox.2024.103329","DOIUrl":"10.1016/j.redox.2024.103329","url":null,"abstract":"<div><p>Alveolar macrophages (AM) are key effectors of the immune response and are essential for host responses to <em>S. pneumoniae.</em> Mitochondria are highly dynamic organelles whose function aids in regulating the cell cycle, innate immunity, autophagy, redox signaling, calcium homeostasis, and mitochondrial quality control in AM. In response to cellular stress, mitochondria can engage in stress-induced mitochondrial hyperfusion (SIMH). The current study aimed to investigate the role of Mfn1 on mitochondrial control of reactive oxygen species (ROS) in AMs and the role of Mfn1 deficiency on immune responses to <em>S. pneumoniae</em>. Compared to Mfn1^FloxCre− controls, there were distinct histological differences in lung tissue collected from Mfn1^{Floxed; CreLysM} mice, with less injury and inflammation observed in mice with Mfn1 deficient myeloid cells. There was a significant decrease in lipid peroxidation and ROS production in Mfn1 deficient AM that was associated with increased superoxide dismutase (SOD) and antioxidant activity. Our findings demonstrate that Mfn1 deficiency in myeloid cells decreased inflammation and lung tissue injury during <em>S. pneumoniae</em> infection.</p></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213231724003070/pdfft?md5=23708ce69501646eb9b09d409d1803cd&pid=1-s2.0-S2213231724003070-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142089743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic induction of ferroptosis by targeting HERC1-NCOA4 axis to enhance the photodynamic sensitivity of osteosarcoma","authors":"","doi":"10.1016/j.redox.2024.103328","DOIUrl":"10.1016/j.redox.2024.103328","url":null,"abstract":"<div><p>Over the past 30 years, the survival rate for osteosarcoma (OS) has remained stagnant, indicating persistent challenges in diagnosis and treatment. Photodynamic therapy (PDT) has emerged as a novel and promising treatment modality for OS. Despite apoptosis being the primary mechanism attributed to PDT, it fails to overcome issues such as low efficacy and resistance. Ferroptosis, a Fe²⁺-dependent cell death process, has the potential to enhance PDT's efficacy by increasing reactive oxygen species (ROS) through the Fenton reaction. In this study, we investigated the anti-tumor mechanism of PDT and introduced an innovative therapeutic strategy that synergistically induces apoptosis and ferroptosis. Furthermore, we have identified HERC1 as a pivotal protein involved in the ubiquitination and degradation of NCOA4, while also uncovering a potential regulatory factor involving NRF2. Ultimately, by targeting the HERC1-NCOA4 axis during PDT, we successfully achieved full activation of ferroptosis, which significantly enhanced the anti-tumor efficacy of PDT. In conclusion, these findings provide new theoretical evidence for further characterizing mechanism of PDT and offer new molecular targets for the treatment of OS.</p></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213231724003069/pdfft?md5=4811240ae33f647745a8aebbd51f7ca1&pid=1-s2.0-S2213231724003069-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142096296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}