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Theoretical studies on the antioxidant activity of potential marine xanthones. 关于潜在海洋氧杂蒽酮抗氧化活性的理论研究。
IF 3.6 3区 生物学
Free Radical Research Pub Date : 2024-12-15 DOI: 10.1080/10715762.2024.2438918
Phan Thi Thuy, Nguyen Xuan Ha
{"title":"Theoretical studies on the antioxidant activity of potential marine xanthones.","authors":"Phan Thi Thuy, Nguyen Xuan Ha","doi":"10.1080/10715762.2024.2438918","DOIUrl":"https://doi.org/10.1080/10715762.2024.2438918","url":null,"abstract":"<p><p>In this study, a quantum chemical exploration was conducted to assess the antioxidant activity of xanthones isolated from marine sources, focusing on thermodynamics and kinetics within simulated physiological environments. DFT analysis revealed that xanthones such as 1,4,7-trihydroxy-6-methylxanthone (<b>1</b>), 1,4,5-trihydroxy-2-methylxanthone (<b>2</b>), arthone C (<b>3</b>), 2,3,4,6,8-pentahydroxy-1-methylxanthone (<b>4</b>), sterigmatocystin (<b>5</b>), oxisterigmatocystin C (<b>6</b>), and oxisterigmatocystin D (<b>7</b>) favor the SPLET pathway in water and the FHT pathway in lipid environments. The kinetic study of these xanthones reacting with the hydroperoxyl radical (HOO•) was conducted using the formal hydrogen atom transfer (FHT) mechanism and the single electron transfer (SET) mechanism. The results showed that compounds <b>1</b>-<b>4</b> exhibited antioxidant activities in aqueous environments surpassing that of the reference compound Trolox, with rate constants ranging from 2.02 x 10<sup>5</sup> to 9.44 x 10<sup>7</sup> M<sup>-1</sup>·s<sup>-1</sup>. In lipid environments, compounds <b>1</b> and <b>2</b> also demonstrated higher rate constants than Trolox. Additionally, molecular docking and molecular dynamics analysis suggested that xanthones <b>1</b>-<b>7</b> potentially inhibit the pro-oxidant effect of the Keap1 enzyme, highlighting their promise as both antiradicals and enzyme inhibitors.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-15"},"PeriodicalIF":3.6,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827681","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
Urban aerosol particulate matter promotes cellular senescence through mitochondrial ROS-mediated Akt/Nrf2 downregulation in human retinal pigment epithelial cells.
IF 3.6 3区 生物学
Free Radical Research Pub Date : 2024-12-08 DOI: 10.1080/10715762.2024.2438919
Beom Su Park, EunJin Bang, Hyun Hwangbo, Gi-Young Kim, JaeHun Cheong, Yung Hyun Choi
{"title":"Urban aerosol particulate matter promotes cellular senescence through mitochondrial ROS-mediated Akt/Nrf2 downregulation in human retinal pigment epithelial cells.","authors":"Beom Su Park, EunJin Bang, Hyun Hwangbo, Gi-Young Kim, JaeHun Cheong, Yung Hyun Choi","doi":"10.1080/10715762.2024.2438919","DOIUrl":"https://doi.org/10.1080/10715762.2024.2438919","url":null,"abstract":"<p><p>Urban aerosol particulate matter (UPM) is widespread in the environment, and its concentration continues to increase. Several recent studies have reported that UPM results in premature cellular senescence, but few studies have investigated the molecular basis of UPM-induced senescence in retinal pigment epithelial (RPE) cells. In this study, we primarily evaluated UPM-induced premature senescence and the protective function of nuclear factor erythroid 2-related factor 2 (Nrf2) in human RPE ARPE-19 cells. The findings indicated that UPM exposure substantially induced premature cellular senescence in ARPE-19 cells, as observed by increased β-galactosidase activity, expression levels of senescence-associated marker proteins, and senescence-associated phenotypes. Such UPM-induced senescence is associated with mitochondrial oxidative stress-mediated phosphatidylinositol 3'-kinase/Akt/Nrf2 downregulation. Sulforaphane-mediated Nrf2 activation Sulforaphane-mediated upregulation of phosphorylated Nrf2 suppressed the decrease in its target antioxidant gene, NAD(P)H quinone oxidoreductase 1, under UPM, which notably prevented ARPE-19 cells from UPM-induced cellular senescence. By contrast, Nrf2 knockdown exacerbated cellular senescence and promoted oxidative stress. Collectively, our results demonstrate the regulatory role of Nrf2 in UPM-induced senescence of RPE cells and suggest that Nrf2 is a potential molecular target.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-13"},"PeriodicalIF":3.6,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794468","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
The effect of taraxerol acetate extracted from dandelion on alleviating oxidative stress responses in vitro.
IF 3.6 3区 生物学
Free Radical Research Pub Date : 2024-12-05 DOI: 10.1080/10715762.2024.2437640
Jiaquan Lu, Siying Yi, Shuna Wang, Yafang Shang, Shaohua Yang, Kai Cui
{"title":"The effect of taraxerol acetate extracted from dandelion on alleviating oxidative stress responses <i>in vitro</i>.","authors":"Jiaquan Lu, Siying Yi, Shuna Wang, Yafang Shang, Shaohua Yang, Kai Cui","doi":"10.1080/10715762.2024.2437640","DOIUrl":"https://doi.org/10.1080/10715762.2024.2437640","url":null,"abstract":"<p><p>Oxidative stress can be alleviated by antioxidants intakes. Taraxerol acetate (TA), a natural triterpenoid extracted from dandelions, may reduce the risk of metabolic disorders by regulating oxidative stress. In the study, we investigated the effects of TA in relieving oxidative stress in murine intestinal epithelial cells using multiomics techniques. Here, we found that TA activated the antioxidant defense system. Total antioxidant capacity (T-AOC) and Catalase (CAT) activity notably increased after TA treatment. Additionally, TA treatment effectively reduced the levels of lactate dehydrogenase (LDH) and malonaldehyde (MDA) and alleviated H<sub>2</sub>O<sub>2</sub>-induced oxidative stress. Furthermore, TA induced significant changes in the levels of 30 important metabolites. Specifically, it activated the complement and coagulation cascades, NF-κB and MAPK and glycerophospholipid pathways, resulting in altered transcript levels of related genes, such as Serpinb9e, SCD2, Hspa1b, and Hspa1a. Thus, the results demonstrated that TA potentially could promote health by alleviating H<sub>2</sub>O<sub>2</sub>-induced oxidative damage and provide valuable insights for its further development.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-15"},"PeriodicalIF":3.6,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784882","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
Karyoptosis as a novel type of UVB-induced regulated cell death.
IF 3.6 3区 生物学
Free Radical Research Pub Date : 2024-12-03 DOI: 10.1080/10715762.2024.2433986
Weidong Chen, Jiin Byun, Han Chang Kang, Hye Suk Lee, Joo Young Lee, Young Jik Kwon, Yong-Yeon Cho
{"title":"Karyoptosis as a novel type of UVB-induced regulated cell death.","authors":"Weidong Chen, Jiin Byun, Han Chang Kang, Hye Suk Lee, Joo Young Lee, Young Jik Kwon, Yong-Yeon Cho","doi":"10.1080/10715762.2024.2433986","DOIUrl":"https://doi.org/10.1080/10715762.2024.2433986","url":null,"abstract":"<p><p>Karyoptosis is a type of regulated cell death (RCD) characterized by explosive nuclear rupture caused by a loss of nuclear membrane integrity, resulting in the release of genomic DNA and other nuclear components into the cytosol and extracellular environment. The mechanism underlying karyoptosis involves a delicate balance between the following forces: the expansion force exerted by the tightly packed DNA in the nucleus, the resistance provided by the nuclear lamina at the inner nuclear membrane (INM), and the tensile force from the cytoskeleton that helps position the nucleus at the center of the cytoplasm, allowing it to remain maximally expanded. In addition, CREB3, a type II integral membrane protein with DNA-binding ability, tethers chromatin to the INM, providing a tightening force through chromatin interactions that prevent nuclear membrane rupture. UVB radiation can trigger this process, inducing CREB3-FL cleavage and producing CREB3-CF. Therefore, UVB acts as an intrinsic factor in the induction of karyoptosis. Importantly, biochemical analysis of RCD markers shows that karyoptosis is distinct from other forms of cell death, such as apoptosis, autophagy, necroptosis, and pyroptosis. This review explores the mechanisms involved in maintaining nuclear membrane integrity and the role of CREB3 in triggering karyoptosis and provides brief suggestions on the potential implications for targeting cancer cells.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-15"},"PeriodicalIF":3.6,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767705","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
Effects of autophagy on the selective death of human breast cancer cells exposed to plasma-activated Ringer's lactate solution.
IF 3.6 3区 生物学
Free Radical Research Pub Date : 2024-12-03 DOI: 10.1080/10715762.2024.2433965
Taishi Yamakawa, Ayako Tanaka, Camelia Miron, Kae Nakamura, Hiroaki Kajiyama, Shinya Toyokuni, Masaaki Mizuno, Masaru Hori, Hiromasa Tanaka
{"title":"Effects of autophagy on the selective death of human breast cancer cells exposed to plasma-activated Ringer's lactate solution.","authors":"Taishi Yamakawa, Ayako Tanaka, Camelia Miron, Kae Nakamura, Hiroaki Kajiyama, Shinya Toyokuni, Masaaki Mizuno, Masaru Hori, Hiromasa Tanaka","doi":"10.1080/10715762.2024.2433965","DOIUrl":"https://doi.org/10.1080/10715762.2024.2433965","url":null,"abstract":"<p><p>Plasma-activated Ringer's lactate (PAL) solution prepared by irradiating an intravenous solution with a non-equilibrium atmospheric pressure plasma is a potential new cancer therapy having no side effects. However, the induction of autophagy to avoid cell death has been confirmed to occur following exposure to PAL solution. It is thought that the antitumor effect of PAL solution could be weakened by this process, which is meant to maintain homeostasis in cells and assists tumorigenesis. Thus, it would be helpful to devise PAL-based cancer therapies that inhibit autophagy. Unfortunately, it is not yet clear which substances in PAL solution promote autophagy. The present work examined the mechanism by which PAL solution induces autophagy when treating MCF-7 human breast cancer cells. Autophagy was found to be temporarily induced upon exposure to PAL solution, suggesting that this effect contributes to cell proliferation. Although autophagy is associated with reactive oxygen and nitrogen species and/or acidic environments, in this study, significant autophagy was observed using a PAL solution diluted 1/256x without these stressors. Acetate, glyoxylate and 2,3-dimethyltartrate in the PAL solution were determined to promote autophagy. Interestingly, 2,3-dimethyltartrate was found to either induce cell death or autophagy depending on the concentration.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-12"},"PeriodicalIF":3.6,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767793","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
"Reductive stress" the overlooked side of cellular redox modulation in cancer: opportunity for design of next generation redox chemotherapeutics. 癌症细胞氧化还原调节中被忽视的 "还原应激":设计下一代氧化还原化疗药物的机遇。
IF 3.6 3区 生物学
Free Radical Research Pub Date : 2024-11-28 DOI: 10.1080/10715762.2024.2433988
Amit Kunwar, J Aishwarya
{"title":"\"Reductive stress\" the overlooked side of cellular redox modulation in cancer: opportunity for design of next generation redox chemotherapeutics.","authors":"Amit Kunwar, J Aishwarya","doi":"10.1080/10715762.2024.2433988","DOIUrl":"https://doi.org/10.1080/10715762.2024.2433988","url":null,"abstract":"<p><p>The last three decades of redox biology research have been dominated by the term \"oxidative stress\" since it was first coined by Helmut Sies to represent a form of cellular redox modulation characterized by redox imbalance toward overproduction of oxidants. Almost every pathological condition, including cancer, has been linked with oxidative stress and so forth; targeting oxidative stress became the strategy for the new drug discovery with anticancer drugs aiming to selectively induce oxidative stress in cancerous cells while antioxidants aiming to prevent carcinogenesis as prophylactic agents. Time has now come to realize, how harmful the other side of the cellular redox spectrum, \"reductive stress,\" characterized by redox imbalance toward the accumulation of reducing equivalents, maybe during carcinogenesis, and to tap its potential for the design of next-generation chemotherapeutic agents. Adjuvants-causing reductive stress may also work synergistically with radiation therapy under hypoxia to achieve better tumor control. Keeping this evolving field into account, the present review provides a current understating of the role of reductive stress in carcinogenesis, the status of reductive stress-based chemotherapeutic agents with particular emphasis on sulfhydryl and selenium-containing compounds and the gap areas that need to be addressed in future.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-14"},"PeriodicalIF":3.6,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738852","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
Catechol-derived Mannich bases: radical regulatory properties, cytotoxicity and interaction with biomolecules. 儿茶酚衍生曼尼希碱:自由基调节特性、细胞毒性以及与生物大分子的相互作用。
IF 3.6 3区 生物学
Free Radical Research Pub Date : 2024-11-27 DOI: 10.1080/10715762.2024.2433985
Gvozdev M Y, Turomsha I S, Loginova N V, Varfolomeeva E Y, Kovalev R A, Fedorova N D, Ksendzova G A, Osipovich N P, Sverdlov R L
{"title":"Catechol-derived Mannich bases: radical regulatory properties, cytotoxicity and interaction with biomolecules.","authors":"Gvozdev M Y, Turomsha I S, Loginova N V, Varfolomeeva E Y, Kovalev R A, Fedorova N D, Ksendzova G A, Osipovich N P, Sverdlov R L","doi":"10.1080/10715762.2024.2433985","DOIUrl":"https://doi.org/10.1080/10715762.2024.2433985","url":null,"abstract":"<p><p>Free radicals are ubiquitous in biological systems, being responsible for pathogenesis of degenerative diseases and participating in vitally important biochemical processes, which are mediated by radical regulatory agents. The effects of the aliphatic amine substituents in the catechol-derived Mannich bases on their antioxidant and pro-oxidant activity were investigated. It has been found that the presence of catechol moiety in the structure of Mannich bases allows them to act as Cu(II) reductants, efficient Fe(II) chelators and potent DPPH radical scavengers. It has been found that the plausible mechanism of the DPPH radical scavenging proceeds <i>via</i> quinone formation, followed by their interaction with ethanol <i>via</i> the Michael addition reaction. In the neutrophil respiratory burst assay, several compounds have demonstrated a weak antioxidant activity at the micromolar level (0.1-10 µM), whereas at the millimolar level (0.1 mМ) a strong pro-oxidant effect has been observed. Additionally, at the highest used concentrations a pronounced cytotoxicity against dermal fibroblasts DF-2 and an immunosuppressive effect against T-lymphocytes have been observed for all the synthesized compounds. It has been demonstrated that the oxidation of catechols in the presence of low-molecular thiols results in the formation of covalent adducts, which provides an insight into their cytotoxicity and detoxification pathways.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-12"},"PeriodicalIF":3.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738883","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
Modifications of DJ-1 in which pI shifts to acidic in red blood cells a potential biomarker for Parkinson's disease at early stages. 红细胞中 pI 变为酸性的 DJ-1 修饰是帕金森病早期阶段的潜在生物标志物。
IF 3.6 3区 生物学
Free Radical Research Pub Date : 2024-11-22 DOI: 10.1080/10715762.2024.2430536
Kohei Matsuda, Yuichiro Mita, Kazumasa Saigoh, Yoshiro Saito, Noriko Noguchi
{"title":"Modifications of DJ-1 in which pI shifts to acidic in red blood cells a potential biomarker for Parkinson's disease at early stages.","authors":"Kohei Matsuda, Yuichiro Mita, Kazumasa Saigoh, Yoshiro Saito, Noriko Noguchi","doi":"10.1080/10715762.2024.2430536","DOIUrl":"https://doi.org/10.1080/10715762.2024.2430536","url":null,"abstract":"<p><p>Parkinson's disease (PD) is one of the most common neurodegenerative diseases, the incidence of which increases with age. However, since there is no fundamental treatment or methods for early diagnosis, new methods of treatment and diagnosis are urgently needed. We focused on post-translational modifications of DJ-1, which is encoded by the familial PD-causative gene <i>PARK7</i> in red blood cells (RBCs). DJ-1 has three cysteines (Cys46, Cys53, and Cys106), with Cys106 being preferentially oxidized. We previously reported that sulfinated/sulfonated Cys106 DJ-1 (oxDJ-1) is increased in the RBCs of PD patients. In this study, we analyzed RBC-derived DJ-1 from PD patients and control subjects by 2-dimensional electrophoresis. We found that the ratio of the spot of DJ-1 with a more acidic isoelectric point than oxDJ-1 was increased more significantly than that of oxDJ-1 in RBCs from patients at the early stage of unmedicated PD and decreased with the progression of PD stage and treatment. Furthermore, we revealed that this acidic spot of DJ-1 increased upon exposure to H<sub>2</sub>O<sub>2</sub>. However, when either Cys53 or Cys106 of DJ-1 was replaced with serine, there was no significant increase in the acidic spot caused by H<sub>2</sub>O<sub>2</sub>. In this study, we propose a new biomarker for early diagnosis of PD using both the ratios of oxDJ-1 to total DJ-1 and the acidic spot of DJ-1 to total DJ-1.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-10"},"PeriodicalIF":3.6,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686456","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
Accumulation of polyunsaturated lipids fuels ferroptosis to promote liver failure after extended hepatectomy in mice. 多不饱和脂质的积累助长了铁变态反应,从而导致小鼠肝切除术后肝功能衰竭。
IF 3.6 3区 生物学
Free Radical Research Pub Date : 2024-11-08 DOI: 10.1080/10715762.2024.2423691
Can Huang, Jian Gan, Xiangyue Mo, Qingping Li, Leyi Liao, Biao Wang, Xianqiu Wu, Hanbiao Liang, Chen Xie, Tianzhou Peng, Yang Lei, Baoxiong Zhuang, Minghui Zeng, Yonghong Peng, Yisi Chen, Cuiting Liu, Jie Zhou, Kai Wang, Chuanjiang Li
{"title":"Accumulation of polyunsaturated lipids fuels ferroptosis to promote liver failure after extended hepatectomy in mice.","authors":"Can Huang, Jian Gan, Xiangyue Mo, Qingping Li, Leyi Liao, Biao Wang, Xianqiu Wu, Hanbiao Liang, Chen Xie, Tianzhou Peng, Yang Lei, Baoxiong Zhuang, Minghui Zeng, Yonghong Peng, Yisi Chen, Cuiting Liu, Jie Zhou, Kai Wang, Chuanjiang Li","doi":"10.1080/10715762.2024.2423691","DOIUrl":"10.1080/10715762.2024.2423691","url":null,"abstract":"<p><strong>Background: </strong>Post-hepatectomy liver failure (PHLF) is a fatal complication of hepatectomy. However, the mechanism of hepatocyte injury in PHLF remains elusive.</p><p><strong>Methods: </strong>PHLF was induced by extended 86% hepatectomy (eHx) in mice. Lipidomics was performed to investigate the eHx-induced lipid alteration in the residual liver. Ferroptosis was assessed to screen the hepatocyte injury induced by eHx. The therapeutic effects of ferrostatin-1 (Fer-1) on PHLF were evaluated.</p><p><strong>Results: </strong>PHLF was induced by eHx with elevation in markers of hepatocyte injury and mortality in mice within 48 h after surgery. eHx-induced hepatocyte injury was manifested by hepatocyte enlargement and hepatocyte death with glycogen depletion and lipid accumulation. Lipidomics revealed that eHx induced the accumulation of ferroptosis-favored polyunsaturated lipids. Ferroptosis was found to mediate the eHx-induced hepatocyte death in the residual liver during the development of PHLF. Fer-1 could attenuate the eHx-induced ferroptotic hepatocyte death and PHLF in mice.</p><p><strong>Conclusions: </strong>Ferroptosis partly mediates the eHx-induced hepatocyte injury during the development of PHLF. Accumulation of polyunsaturated lipids in hepatocytes may promote eHx-induced ferroptosis, and targeting lipid peroxidation is a potential therapeutic strategy for PHLF.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-15"},"PeriodicalIF":3.6,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603925","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
Ferritin with methylglyoxal produces reactive oxygen species but remains functional. 含有甲基乙二醛的铁蛋白会产生活性氧,但仍能发挥作用。
IF 3.6 3区 生物学
Free Radical Research Pub Date : 2024-11-07 DOI: 10.1080/10715762.2024.2417281
Adriana Rybnikářová, Richard Buchal, Jan Pláteník
{"title":"Ferritin with methylglyoxal produces reactive oxygen species but remains functional.","authors":"Adriana Rybnikářová, Richard Buchal, Jan Pláteník","doi":"10.1080/10715762.2024.2417281","DOIUrl":"https://doi.org/10.1080/10715762.2024.2417281","url":null,"abstract":"<p><p>Iron is necessary for life, but the simultaneous iron-catalyzed formation of reactive oxygen species (ROS) is involved in pathogenesis of many diseases. One of them is diabetes mellitus, a widespread disease with severe long-term complications, including neuropathy, retinopathy, and nephropathy. Much evidence points to methylglyoxal, a potent glycating agent, as the key mediator of diabetic complications. In diabetes, there is also a peculiar dysregulation of iron homeostasis, leading to an expansion of redox-active iron. This <i>in vitro</i> study focuses on the interaction of methylglyoxal with ferritin, which is the main cellular protein for iron storage. Methylglyoxal effectively liberates iron from horse spleen ferritin, as well as synthetic iron cores; in both cases, it is partially mediated by superoxide. The interaction of methylglyoxal with ferritin increases the production of hydrogen peroxide, much above the generation of peroxide by methylglyoxal alone, in an iron-dependent manner. Glycation with methylglyoxal results in structural changes in ferritin. All of these findings can be demonstrated with pathophysiologically relevant (submillimolar) methylglyoxal concentrations. However, the rate of iron release by ascorbate, the ferroxidase activity, or the diameter of gated pores even in intensely glycated ferritin is not altered. In conclusion, although the functional features of ferritin resist alterations due to glycation, the interaction of methylglyoxal with ferritin liberates iron and markedly increases ROS production, both of which could enhance oxidative stress <i>in vivo</i>. Our findings may have implications for the pathogenesis of long-term diabetic complications, as well as for the use of ferritin as a nanocarrier in chemotherapy.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-21"},"PeriodicalIF":3.6,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603927","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
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