Free Radical Research最新文献_第9页

Protective effects of sinensetin against oxidative stress damage induced by AAPH in the brain-gut. 青肠素对AAPH诱导的脑-肠氧化应激损伤的保护作用。

IF 3.6 3区生物学

Free Radical Research Pub Date : 2025-05-01 Epub Date: 2025-06-10 DOI: 10.1080/10715762.2025.2514799

Tingting Jin, Menghui He, Na Li, Ying He, Feng He

引用次数: 0

Dioscin induces ferroptosis to suppress the metastasis of gastric cancer through the SLC7A11/GPX4 axis. 薯蓣皂苷诱导铁下垂通过SLC7A11/GPX4轴抑制胃癌转移。

IF 3.6 3区生物学

Free Radical Research Pub Date : 2025-05-01 Epub Date: 2025-06-13 DOI: 10.1080/10715762.2025.2515202

Doudou Lu, Ling Yuan, Zhaozhao Wang, Duojie Xu, Fandi Meng, Shumin Jia, Yahong Li, Weiqiang Li, Yi Nan

{"title":"Dioscin induces ferroptosis to suppress the metastasis of gastric cancer through the SLC7A11/GPX4 axis.","authors":"Doudou Lu, Ling Yuan, Zhaozhao Wang, Duojie Xu, Fandi Meng, Shumin Jia, Yahong Li, Weiqiang Li, Yi Nan","doi":"10.1080/10715762.2025.2515202","DOIUrl":"10.1080/10715762.2025.2515202","url":null,"abstract":"The prognosis of gastric cancer (GC) remains poor due to metastases and resistance to chemotherapy. Ferroptosis is a novel cell death regulation mode characterized by iron dependence and lipid peroxidation. Dioscin, a compound extracted from the Paris polyphylla rhizomes roots, has been shown to have an inhibitory effect on cancers. However, whether it induces ferroptosis to participate in anti-cancer metastasis remains unclear. The ability of gastric cancer cells to invade and migrate was evaluated by wound healing and transwell assays. Malondialdehyde (MDA), glutathione (GSH) assay kit, and dichlorofluorescin diacetate (DCFH-DA) fluorescent probes were used to detect ferroptosis in gastric cancer cells. The expression levels of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot methods. The rescue assay was performed by adding Ferrostatin-1 (Fer-1) co-treatment to verify that Dioscin inhibited gastric cancer metastasis by participating in ferroptosis. Dioscin inhibited gastric cancer cells' wound healing, migration, and invasion process. In addition, Dioscin increased the level of reactive oxygen species (ROS) and MDA while decreasing GSH level, and induced ferroptosis of gastric cancer cells. Fer-1, an inhibitor of ferroptosis, could reverse the effect of Dioscin. In terms of mechanism, Dioscin induced ferroptosis through SLC7A11/GPX4 axis and was involved in the regulation of inhibiting metastasis of gastric cancer. These results suggested that Dioscin was involved in anti-cancer metastasis by inducing ferroptosis.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"426-441"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Selenomethionine enhances transplant organ preservation by attenuating oxidative stress-induced proteolysis in rats. 硒代蛋氨酸通过减弱大鼠氧化应激诱导的蛋白水解而增强移植器官保存。

IF 3.6 3区生物学

Free Radical Research Pub Date : 2025-05-01 Epub Date: 2025-06-11 DOI: 10.1080/10715762.2025.2516844

Paul Emir Hasuoka, Franco Tonelli, Leonardo Mariño-Repizo, Pablo Pacheco

{"title":"Selenomethionine enhances transplant organ preservation by attenuating oxidative stress-induced proteolysis in rats.","authors":"Paul Emir Hasuoka, Franco Tonelli, Leonardo Mariño-Repizo, Pablo Pacheco","doi":"10.1080/10715762.2025.2516844","DOIUrl":"10.1080/10715762.2025.2516844","url":null,"abstract":"Selenomethionine (SeMet) increases glutathione peroxidase (GPx) activity, a seleno-enzyme with an antioxidant function that counteracts reactive oxygen species (ROS). After ablation, transplant organs generate ROS during irrigation-reperfusion injury. GPx1 can be downregulated during hypoxia in ablated organs. ROS can oxidize proteins, inducing proteolysis, which compromises the transplant outcome. SeMet administration to living donors can decrease proteolysis in transplant organs, improving their preservation. Accordingly, SeMet was administered to rats for 7 days. After this period, the liver, heart, and kidneys were ablated, and proteins extracted at different postmortem intervals (PMI). Total protein analysis showed a lower protein concentration decrease in kidneys and heart from SeMet-supplemented rats after a 6 hs PMI. Molecular weight changes of proteins to proteolysis products (PPs) were studied by size exclusion chromatography (SEC). SeMet decreased PPs (<29.5 kDa) in the liver, kidneys, and heart. Specific analysis of GPx1 proteolysis by affinity chromatography coupled to inductively coupled plasma mass spectrometry (AF-ICP-MS) showed that SeMet administration decreased GPx1 proteolysis 24% in the liver and 16.8% in the heart. SeMet administration reduced the proteolysis velocity of GPx1 (VGPx1) in heart. SeMet administration to living donors for seven days decreased proteolysis in transplant organs, improving its conservation.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"442-451"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enhanced cytotoxicity against cancer cells by acetylation of a planar catechin analog. 平面儿茶素类似物乙酰化增强对癌细胞的细胞毒性。

IF 2.9 3区生物学

Free Radical Research Pub Date : 2025-05-01 Epub Date: 2025-07-04 DOI: 10.1080/10715762.2025.2525185

Hiromu Ito, Yoshimi Shoji, Yuki Itabashi, Ken-Ichiro Matsumoto, Kei Ohkubo, Kiyoshi Fukuhara, Ikuo Nakanishi

{"title":"Enhanced cytotoxicity against cancer cells by acetylation of a planar catechin analog.","authors":"Hiromu Ito, Yoshimi Shoji, Yuki Itabashi, Ken-Ichiro Matsumoto, Kei Ohkubo, Kiyoshi Fukuhara, Ikuo Nakanishi","doi":"10.1080/10715762.2025.2525185","DOIUrl":"10.1080/10715762.2025.2525185","url":null,"abstract":"Catechin is a major antioxidant and also shows anti-cancer effect. We have synthesized a catechin analog possessing a planar structure, planar catechin, which has 10-fold larger radical-scavenging activity than the parental (+)-catechin, and demonstrated that the planar catechin showed a significant cytotoxicity in cancer cells. However, the planar catechin has a possibility to lose the innate activity before reaching target cells, because of the higher reactivity with other biological molecules. In this study, we introduced acetyl groups to the phenolic hydroxy groups, which are considered as active sites of the planar catechin, in order to protect from the oxidation of the planar catechin, and examined the effects on cells regarding the toxicity. The acetylated planar catechin showed a remarkable cytotoxicity compared to the original planar catechin, especially in cancer cells, whereas the superoxide scavenging activity of the acetylated planar catechin was weak. On the other hand, after the acetylated planar catechin was treated with esterase, the enhanced superoxide scavenging activity was confirmed by an electron paramagnetic resonance technique. These results indicate that the activity of the planar catechin was maintained by acetylation of the phenolic hydroxy groups and the deprotection by intracellular esterase restored the activity, leading to the induction of the severe cytotoxicity.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"480-486"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Thioredoxin improves contact dermatitis through an anti-inflammatory mechanism different from glucocorticoids. 硫氧还蛋白通过不同于糖皮质激素的抗炎机制改善接触性皮炎。

IF 2.9 3区生物学

Free Radical Research Pub Date : 2025-05-01 Epub Date: 2025-07-26 DOI: 10.1080/10715762.2025.2536295

Cuixue Wang, Jinquan Wang, Jiedong Zhou, Zhenbo Gong, Atsushi Fukunaga, Junji Yodoi, Akira Yamauchi, Hai Tian

{"title":"Thioredoxin improves contact dermatitis through an anti-inflammatory mechanism different from glucocorticoids.","authors":"Cuixue Wang, Jinquan Wang, Jiedong Zhou, Zhenbo Gong, Atsushi Fukunaga, Junji Yodoi, Akira Yamauchi, Hai Tian","doi":"10.1080/10715762.2025.2536295","DOIUrl":"10.1080/10715762.2025.2536295","url":null,"abstract":"Thioredoxin (TRX), a redox-regulatory protein of 12 kDa, plays an essential role in modulating oxidative stress and mediating inflammatory processes. In this study, we compared and analyzed the anti-inflammatory effects of topically applied recombinant human TRX (rhTRX), hydrocortisone, and their combination on murine models of contact dermatitis (CD). Topical application of rhTRX, hydrocortisone, and their synergistic combination notably ameliorated ear edema, reduced neutrophilic infiltration within the ear tissues and suppressed the production of cytokines. We explored the distinct anti-inflammatory mechanisms of rhTRX versus hydrocortisone in phorbol-12-myristate-13-acetate (PMA)-induced PAM212 cells. These treatments collectively downregulated the phosphorylation of p-JNK and p-P38 mitogen-activated protein kinases (MAPKs) in the cells. In addition, rhTRX did not impact the proliferation of CD4+ and CD8+ T lymphocytes. Notably, rhTRX directly downregulated macrophage migration inhibitory factor (MIF), whereas it had no effects on the glucocorticoid-induced leucine zipper (GILZ). Collectively, these findings delineated that rhTRX ameliorated CD by curtailing MAPK pathway, and enhancing glucocorticoid responsiveness through the targeted downregulation of MIF. Consequently, it holds promise as a therapeutic agent for the treatment of CD and warrants further investigation in translational research.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"518-530"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144663887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Heated tobacco product emissions induce DNA damage in human bronchial epithelial cells via radical formation. 加热烟草制品排放通过自由基形成诱导人支气管上皮细胞DNA损伤。

IF 2.9 3区生物学

Free Radical Research Pub Date : 2025-05-01 Epub Date: 2025-06-23 DOI: 10.1080/10715762.2025.2521633

Michele Davigo, Victoria Claudino Bastos, Kato Mengels, Alex Mommers, Frederik-Jan van Schooten, Jacco J Briedé, Phyllis Jessen, Antoon Opperhuizen, Reinskje Talhout, Sabine A S Langie, Alexander H V Remels

{"title":"Heated tobacco product emissions induce DNA damage in human bronchial epithelial cells via radical formation.","authors":"Michele Davigo, Victoria Claudino Bastos, Kato Mengels, Alex Mommers, Frederik-Jan van Schooten, Jacco J Briedé, Phyllis Jessen, Antoon Opperhuizen, Reinskje Talhout, Sabine A S Langie, Alexander H V Remels","doi":"10.1080/10715762.2025.2521633","DOIUrl":"10.1080/10715762.2025.2521633","url":null,"abstract":"IQOS is a heated tobacco product (HTP) claimed to be less harmful than regular cigarettes. It is unknown whether IQOS emissions contain radicals, cause DNA damage or affect the expression of DNA repair markers in human bronchial epithelial cells. This has important implications as IQOS diffusion is quickly growing, but little toxicological and genotoxic information on its emissions is available. Therefore, we determined the presence of radicals in cigarette smoke extract (CSE) and IQOS extract (IQOSE) by Electron Spin Resonance (ESR) spectroscopy and measured their levels of Tobacco-Specific Nitrosamines (TSNAs) with liquid chromatography-mass spectrometry (LC-MS). Next, DNA damage induced by CSE and IQOSE was determined by means of the Fpg-modified comet assay in human bronchial epithelial cells (BEAS-2B). Finally, the mRNA and protein levels of DNA repair markers in response to both extracts were evaluated. CSE contained significantly more reactive oxygen species (ROS) and TSNAs, whereas more carbon/nitrogen-centered radicals were detected in IQOSE. After 1 h exposure, 3%CSE and 5%IQOSE caused DNA oxidation, while 5%IQOSE also induced DNA strand breaks and alkali-labile sites. Exposure of cells to 1% and 3% IQOSE for 4 h upregulated the expression of DNA repair genes, whereas no significant impact on DNA repair protein levels was observed. This study shows that IQOS extract contains significant amounts of radicals and TSNAs, can induce DNA damage and increase the expression of DNA repair genes in human bronchial epithelial cells. Whether IQOS use is associated with higher risk of developing lung cancer remains to be determined.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"463-479"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mitochondrial electron transport chain disruption and oxidative stress in lipopolysaccharide-induced cardiac dysfunction in rats and mice. 脂多糖诱导大鼠和小鼠心功能障碍的线粒体电子传递链断裂和氧化应激。

IF 3.6 3区生物学

Free Radical Research Pub Date : 2025-05-01 Epub Date: 2025-05-15 DOI: 10.1080/10715762.2025.2503844

Agda Aline Pereira de Sousa, Leonardo da Silva Chaves, Heberty Tarso Facundo

{"title":"Mitochondrial electron transport chain disruption and oxidative stress in lipopolysaccharide-induced cardiac dysfunction in rats and mice.","authors":"Agda Aline Pereira de Sousa, Leonardo da Silva Chaves, Heberty Tarso Facundo","doi":"10.1080/10715762.2025.2503844","DOIUrl":"10.1080/10715762.2025.2503844","url":null,"abstract":"Sepsis, characterized by severe systemic inflammation and an excessive immune response to infection, is frequently triggered by bacterial endotoxins like lipopolysaccharide (LPS) from Gram-negative bacteria. Moreover, sepsis-induced cardiac dysfunction remains a leading cause of mortality. This study aims to elucidate the effects of LPS-induced cardiac injury on mitochondrial damage, oxidative stress, and subsequent cardiac dysfunction. LPS injections (in rats and mice) for three days (1.5 mg/kg) impacted the body weight and increased cardiac TNF-α. Additionally, it decreased mitochondrial complexes I and II activities while complexes III and IV remained unaffected. Disturbed in mitochondrial electron transport chain leads to an increase in reactive oxygen species (ROS). Indeed, LPS treatment significantly increased mitochondrial hydrogen peroxide production, reduced the activity of antioxidant enzymes catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase activity. This was accompanied by decreased mitochondrial and cytosolic sulfhydryl proteins and parallel increased cellular lipid peroxidation in the presence or absence of Fe2+. LPS-treated samples had increased glutathione s-transferase activity, which may be an attempt of the cell to remove toxic lipid peroxidation products. In a more acute Langendorff-perfused rat hearts, LPS infusion (0.5 μg/mL) induced a significant elevation in left ventricular end-diastolic pressure and a decrease in left ventricular developed pressure. These findings elucidate the harmful mitochondrial and oxidative effects of LPS in cardiac tissue and could help the development of targeted therapies to mitigate the adverse effects of sepsis-induced cardiac dysfunction.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"377-391"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Distal substituents effect of 4-oxo-TEMPO derivatives bearing a benzyl group at the 2-position on the reduction resistance toward ascorbate. 远端取代基2位含苄基的4-氧- tempo衍生物对抗坏血酸还原抗性的影响。

IF 3.6 3区生物学

Free Radical Research Pub Date : 2025-05-01 Epub Date: 2025-05-16 DOI: 10.1080/10715762.2025.2503839

Karin Nagahama, Toshihide Yamasaki, Kohei Sano, Takahiro Mukai

{"title":"Distal substituents effect of 4-oxo-TEMPO derivatives bearing a benzyl group at the 2-position on the reduction resistance toward ascorbate.","authors":"Karin Nagahama, Toshihide Yamasaki, Kohei Sano, Takahiro Mukai","doi":"10.1080/10715762.2025.2503839","DOIUrl":"10.1080/10715762.2025.2503839","url":null,"abstract":"Nitroxides, which have unpaired electrons, find diverse applications owing to their characteristic redox and radical chemistries. To fine-tune the properties of nitroxide compounds for various applications, we investigated the effect of distant substituents on their reactivity. We synthesized 4-oxo-2,2,6,6-tetramethylpiperidine-N-oxyl (4-oxo-TEMPO) derivatives with electron-donating or electron-withdrawing groups at the para position of the benzyl group attached to the 2-position. The reactivities of these compounds were evaluated by measuring their second-order reaction rate constants with ascorbate using ESR spectroscopy. Density functional theory (DFT) calculations for each compound revealed a correlation between the charge of the N-O moiety and the second-order reaction rate constant. Notably, even substituents positioned far from the nitroxide center significantly affected the reductive reactivity with ascorbate. These findings suggest that both proximal and distal structural modifications can be leveraged to fine-tune nitroxide properties, providing a basis for the rational design of nitroxides with tailored reactivities.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"369-376"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Luteolin protects human ARPE-19 retinal pigment epithelium cells from blue light-induced phototoxicity through activation of Nrf2/Keap1 signaling. 木犀草素通过激活Nrf2/Keap1信号通路保护人ARPE-19视网膜色素上皮细胞免受蓝光诱导的光毒性。

IF 3.6 3区生物学

Free Radical Research Pub Date : 2025-03-01 Epub Date: 2025-05-14 DOI: 10.1080/10715762.2025.2503832

Ryo Hayakawa, Takeshi Ishii, Taiki Fushimi, Yuki Kamei, Ai Yamaguchi, Kenji Sugimoto, Hitoshi Ashida, Mitsugu Akagawa

{"title":"Luteolin protects human ARPE-19 retinal pigment epithelium cells from blue light-induced phototoxicity through activation of Nrf2/Keap1 signaling.","authors":"Ryo Hayakawa, Takeshi Ishii, Taiki Fushimi, Yuki Kamei, Ai Yamaguchi, Kenji Sugimoto, Hitoshi Ashida, Mitsugu Akagawa","doi":"10.1080/10715762.2025.2503832","DOIUrl":"10.1080/10715762.2025.2503832","url":null,"abstract":"Age-related macular degeneration (AMD), a serious physical and mental health problem worldwide, is the leading cause of irreversible, severe vision impairment and loss in older people. AMD is associated with multiple risk factors, many of which are closely linked to increased oxidative stress. Some studies have suggested that long-term and excessive exposure to blue light may be a potential risk factor for the development or progression of AMD. Recently, we demonstrated that blue light irradiation caused oxidative stress in all-trans-retinal (atRAL)-exposed human ARPE-19 retinal pigment epithelium cells by generating singlet oxygen (1O2), leading to apoptotic cell death. Luteolin, a flavonoid found in various edible plants, has been reported to possess divergent health-promoting properties including anti-oxidative and chemopreventive effects by up-regulating anti-oxidative and phase II detoxifying enzymes through activation of Keap1/Nrf2 signaling. Herein, we verified the cytoprotective action of luteolin against blue light irradiation using atRAL-exposed ARPE-19 cells. Our results established that luteolin effectively prevented blue light-induced apoptosis of ARPE-19 cells by mitigating oxidative stress. We also confirmed that luteolin suppressed intracellular accumulation of 1O2 and formation of atRAL-derived lipofuscin by increased expression of heme oxygenase-1 and aldehyde dehydrogenase 1A1 through activation of Keap1/Nrf2 signaling. Furthermore, our data implied that the luteolin-provoked activation of Keap1/Nrf2 signaling might be due to covalent binding of luteolin o-quinone to the critical cysteinyl thiol in Keap1. The present results suggest that luteolin could be helpful in the prevention and amelioration of blue light-induced retinal degeneration, including AMD.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"356-368"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cigarette smoke induces endoplasmic reticulum stress-associated mucus hypersecretion via orosomucoid 1-like protein 3 in airway epithelia. 香烟烟雾通过气道上皮口躯体样蛋白1- 3诱导内质网应激相关粘液高分泌。

IF 3.6 3区生物学

Free Radical Research Pub Date : 2025-03-01 Epub Date: 2025-05-08 DOI: 10.1080/10715762.2025.2501019

Rui Chen, Yuting Cui, Mary Sau-Man Ip, Judith Choi-Wo Mak

{"title":"Cigarette smoke induces endoplasmic reticulum stress-associated mucus hypersecretion via orosomucoid 1-like protein 3 in airway epithelia.","authors":"Rui Chen, Yuting Cui, Mary Sau-Man Ip, Judith Choi-Wo Mak","doi":"10.1080/10715762.2025.2501019","DOIUrl":"10.1080/10715762.2025.2501019","url":null,"abstract":"Apart from a strong association with childhood-onset asthma, orosomucoid 1-like protein 3 (ORMDL3), an endoplasmic reticulum (ER)-localized transmembrane protein, is also linked with chronic obstructive pulmonary disease (COPD), in which cigarette smoke (CS) is the crucial risk factor. Compared to healthy subjects, COPD patients had elevated ORMDL3 mRNA in well-differentiated primary human bronchial epithelial cells (HBECs). However, its role in COPD remains understudied. We, therefore, hypothesize that ORMDL3 may play an essential role in CS-induced chronic mucus hypersecretion and inflammation via activation of specific unfolded protein response (UPR) pathways under ER stress in primary HBECs. Gene silencing using siRNA for ORMDL3 was performed in submerged culture of primary HBECs before 24-h cigarette smoke medium (CSM) exposure. The mucin, inflammatory and mitochondrial markers, and the activation of the UPR pathways were evaluated. CSM triggered significant induction of ORMDL3 expression at both mRNA and protein level, which was significantly inhibited by silencing ORMDL3. In addition, ORMDL3 knockdown inhibited CSM-induced mucin MUC5AC mRNA and release of inflammatory marker interleukin (IL)-8. Silencing ORMDL3 reduced CSM-induced ER stress via inhibiting the activating transcription factor (ATF)6 and the inositol-requiring enzyme (IRE)1 of the UPR pathways. The involvement of ORMDL3 was demonstrated in mitochondrial dynamics via fusion protein Mfn2 and mitochondrial respiration after CSM stimulation. In conclusion, ORMDL3 is an inducible gene in mediating CS-induced activation of specific ATF6 and IRE1 pathways to regulate mucus hypersecretion and inflammation. Therefore, ORMDL3 may be a promising therapeutic target to treat smoking-associated mucus hypersecretion and inflammation in COPD.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"342-355"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0