Free Radical ResearchPub Date : 2025-01-01Epub Date: 2025-01-07DOI: 10.1080/10715762.2024.2446337
Xue Peng, Xi Tan, Li Dai, Wei Xia, Zhao Wu
{"title":"Exploring the impact of Apelin and Reactive Oxygen Species on autophagy and cell senescence in pre-eclampsia.","authors":"Xue Peng, Xi Tan, Li Dai, Wei Xia, Zhao Wu","doi":"10.1080/10715762.2024.2446337","DOIUrl":"10.1080/10715762.2024.2446337","url":null,"abstract":"<p><p>This research investigates the interplay between Reactive Oxygen Species (ROS) and Apelin (APLN) in regulating autophagy, with implications for placental cell senescence and apoptosis in pre-eclampsia (PE). We manipulated APLN expression using sgRNA to study its effects on ROS levels and subsequent cellular responses. Our findings reveal that APLN overexpression elevates ROS production, accelerating cellular senescence and apoptosis. In contrast, silencing APLN enhances autophagy, thereby diminishing cellular aging and apoptosis. These outcomes were confirmed <i>in vitro</i> and <i>in vivo</i> experiments, establishing a causative relationship between ROS-mediated APLN modulation and altered placental cell dynamics in PE. The results suggest potential therapeutic targets within the ROS and APLN pathways to alleviate detrimental changes in the placenta, offering new strategies for the clinical management of PE. This study emphasizes the crucial role of autophagy in placental health and sets the stage for future investigations into therapeutic interventions for pregnancy-related complications.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"23-48"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876698","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}
Free Radical ResearchPub Date : 2025-01-01Epub Date: 2025-01-08DOI: 10.1080/10715762.2024.2449457
Seher Mese-Tayfur, Tugce Demirel-Yalcıner, Anna Migni, Desirée Bartolini, Francesco Galli, Nesrin Kartal Ozer, Erdi Sozen
{"title":"Modulation of inflammatory signaling by vitamin E metabolites and its therapeutic implications.","authors":"Seher Mese-Tayfur, Tugce Demirel-Yalcıner, Anna Migni, Desirée Bartolini, Francesco Galli, Nesrin Kartal Ozer, Erdi Sozen","doi":"10.1080/10715762.2024.2449457","DOIUrl":"10.1080/10715762.2024.2449457","url":null,"abstract":"<p><p>Naturally occurring vitamin E is a lipophilic plant-derived molecule corresponding to the 2 R forms of alpha-tocopherol. A series of natural analogs or tocochromanols are present in nature, including β-, γ- and δ-tocopherol (βT, γT, δT), the corresponding tocotrienols (αTE, βTE, γTE, δTE) and tocomonoenols. Differences between these analogs as lipophilic antioxidants and modulators of molecular processes suggest specific therapeutic properties against various disorders associated with acute and chronic inflammation. However, hepatic metabolism of these compounds <i>via</i> cytochrome P450-initiated side chain ω-oxidation involves the production of long-chain metabolites (LCMs) followed by intermediate (ICMs) and short-chain metabolites (SCMs), respectively. Despite the initial studies indicating these metabolites as catabolic-end products, recent findings identify their importance in providing biological functions. In this scope, LCMs, especially 13'-carboxychromanols (13'-COOHs), have been reported to hold stronger anti-inflammatory capacity than their unmetabolized precursors due to their ability to inhibit 5-lipoxygenase and cyclooxygenase-catalyzed eicosanoid formation, as well as their modulation of the pro-inflammatory transcriptional protein nuclear factor κB (NF-κB). Also, these LCMs have been reported to enhance detoxification and lipid metabolism pathways associated with cellular inflammation by modulating the nuclear receptors peroxisome proliferator-activated receptor-γ (PPARγ) and pregnane x receptor (PXR). These properties of LCMs will be described in this narrative review article focusing on recent information regarding their bioavailability, anti-inflammatory effects, and mechanisms of action in acute and chronic inflammatory disorders.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":"59 1","pages":"86-101"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055904","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}
Free Radical ResearchPub Date : 2024-12-01Epub Date: 2024-12-28DOI: 10.1080/10715762.2024.2443606
Yuechu Zhao, Xiaoting Liang, Ting Li, Zhuang Shao, Zhi Cao, Yi Zeng, Xiaofei Yan, Qi Chen, Hao Zhou, Weifeng Li, Guifen Cheng, Yaping Jiang, Xin Li, Yuelin Zhang, Bei Hu
{"title":"Apelin deficiency exacerbates cardiac injury following infarction by accelerating cardiomyocyte ferroptosis.","authors":"Yuechu Zhao, Xiaoting Liang, Ting Li, Zhuang Shao, Zhi Cao, Yi Zeng, Xiaofei Yan, Qi Chen, Hao Zhou, Weifeng Li, Guifen Cheng, Yaping Jiang, Xin Li, Yuelin Zhang, Bei Hu","doi":"10.1080/10715762.2024.2443606","DOIUrl":"10.1080/10715762.2024.2443606","url":null,"abstract":"<p><p>Apelin is an endogenous ligand for the Apelin receptor and is a critical protective effector in myocardial infarction (MI). Nevertheless, these protective mechanisms are not fully understood. Ferroptosis is the major driving factor of MI. This study aimed to investigate the effects and underlying regulatory mechanisms of Apelin on cardiomyocyte ferroptosis in MI. A model of MI was induced in adult C57BL/6J wild type (WT) and Apelin knockout (Apelin<sup>-/-</sup>) mice. Cardiac function was examined by echocardiography 4 weeks post-MI. RNA-seq, histochemical analyses, and Western blotting were applied to examine the effects of Apelin knockout on the transcriptome and pathological remodeling following infarction and the molecular mechanisms. Mice neonatal cardiomyocytes (NCMs) were used to establish the serum deprivation/hypoxia (SD/H) model <i>in vitro</i>. Compared with WT mice, Apelin<sup>-/-</sup> mice exhibited more severe impairment of cardiac function and increased fibrosis following infarction. Transcriptome and biochemical analyses revealed the involvement of ferroptosis in mediating Apelin function in MI. Ferroptosis-related proteins were significantly increased post-MI in Apelin<sup>-/-</sup> mice whereas p-AMPK was greatly decreased. Apelin treatment activated the AMPK pathway and thereby inhibited ferroptosis of NCMs induced by SD/H <i>in vitro.</i> These protective effects were partially reversed by AMPK inhibitor. Apelin deficiency aggravated cardiac dysfunction following infarction by activating cardiomyocyte ferroptosis via inhibition of the AMPK pathway. This offers a novel potential therapeutic target for MI treatment.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"854-867"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893271","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}
Free Radical ResearchPub Date : 2024-12-01Epub Date: 2024-12-15DOI: 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":"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":"826-840"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","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}
{"title":"New era of plasma dentistry.","authors":"Kotaro Sato, Hiromasa Tanaka, Yasumasa Okazaki, Masaru Hori, Hideharu Hibi, Shinya Toyokuni","doi":"10.1080/10715762.2024.2446323","DOIUrl":"10.1080/10715762.2024.2446323","url":null,"abstract":"<p><p>Plasma, which was coined by Irving Langmuir in 1928, is the fourth physical state after the solid/liquid/gas phases. Low-temperature plasma (LTP) is a contradictory condition that involves high energy with free radicals at near-body temperatures and was developed through engineering in the 1990's. Research on LTP in engineering and medical fields has rapidly developed since the 2000's. LTP can be applied through direct or indirect exposure, and there are advantages to both methods. In the medical field, LTP has been found to exert several effects, such as wound healing, hemostasis and anticancer effects, mainly based on different levels of oxidative stress. In the dental field, studies have been performed on LTP applications for general dental procedures, such as restorative, periodontal and prosthodontic procedures, and for oral cancer treatment. Many studies have demonstrated the effectiveness of LTP. Compared with other organs, the anatomical characteristic of the oral cavity is easy direct observation, which is highly advantageous for clinical applications. Due to its good accessibility and efficiency, plasma dentistry is expected to be applied to various dental applications in clinics in the near future.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"868-874"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876702","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}
Free Radical ResearchPub Date : 2024-12-01Epub Date: 2024-12-08DOI: 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":"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":"841-853"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","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}
Free Radical ResearchPub Date : 2024-12-01Epub Date: 2024-12-05DOI: 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":"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":"811-825"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","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}
Free Radical ResearchPub Date : 2024-11-01Epub Date: 2024-10-19DOI: 10.1080/10715762.2024.2417286
Paweł Sutkowy, Jarosław Paprocki, Jacek Piechocki, Alina Woźniak
{"title":"The impact of hyperbaric oxygen therapy on the redox balance of patients with diabetic foot syndrome.","authors":"Paweł Sutkowy, Jarosław Paprocki, Jacek Piechocki, Alina Woźniak","doi":"10.1080/10715762.2024.2417286","DOIUrl":"10.1080/10715762.2024.2417286","url":null,"abstract":"<p><p>Diabetic foot wounds associated with oxidative stress are treated with hyperbaric oxygen (HBO), but that may also induce the stress itself; therefore, we studied the effect of HBO treatments on the oxidant-antioxidant balance in the venous blood of patients with diabetic foot syndrome. In addition, blood counts were also examined. 14 male patients (24-74 years), at risk of lower limb amputation were treated with 30 HBO procedures (60 min of the inhalation of pure oxygen at a pressure of 2.5 atm per day, 5 days a week). The control group consisted of 29 healthy male volunteers aged 25-69 years. No members of the group had been subjected to HBO therapy previously (ClinicalTrials.gov, no. NCT06401941). The analyzed redox parameters did not change during the experiment in the patients (<i>p</i> > 0.05). The concentration of thiobarbituric acid reactive substances (TBARS) in the plasma was higher in the patients before the first and after the thirtieth HBO treatments when compared to the control group. In contrast, the TBARS concentration in erythrocytes was lower in the patients after the first treatment vs. the controls. Moreover, the higher activity of catalase in the patients' erythrocytes was noted before the therapy and after the first and last treatments compared to the controls. HBO therapy increased the percentage of monocytes and platelet volume, but it decreased the volume of platelets in the patients' blood. HBO therapy does not affect the oxidant-antioxidant balance disturbed in diabetic foot patients.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"723-732"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461847","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}
Free Radical ResearchPub Date : 2024-11-01Epub Date: 2024-11-08DOI: 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":"733-747"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","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}
{"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":"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":"748-757"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","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}