AntioxidantsPub Date : 2024-11-01DOI: 10.3390/antiox13111343
Upasana Ganguly, Trae Carroll, Keith Nehrke, Gail V W Johnson
{"title":"Mitochondrial Quality Control in Alzheimer's Disease: Insights from <i>Caenorhabditis elegans</i> Models.","authors":"Upasana Ganguly, Trae Carroll, Keith Nehrke, Gail V W Johnson","doi":"10.3390/antiox13111343","DOIUrl":"10.3390/antiox13111343","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a complex neurodegenerative disorder that is classically defined by the extracellular deposition of senile plaques rich in amyloid-beta (Aβ) protein and the intracellular accumulation of neurofibrillary tangles (NFTs) that are rich in aberrantly modified tau protein. In addition to aggregative and proteostatic abnormalities, neurons affected by AD also frequently possess dysfunctional mitochondria and disrupted mitochondrial maintenance, such as the inability to eliminate damaged mitochondria via mitophagy. Decades have been spent interrogating the etiopathogenesis of AD, and contributions from model organism research have aided in developing a more fundamental understanding of molecular dysfunction caused by Aβ and toxic tau aggregates. The soil nematode <i>C. elegans</i> is a genetic model organism that has been widely used for interrogating neurodegenerative mechanisms including AD. In this review, we discuss the advantages and limitations of the many <i>C. elegans</i> AD models, with a special focus and discussion on how mitochondrial quality control pathways (namely mitophagy) may contribute to AD development. We also summarize evidence on how targeting mitophagy has been therapeutically beneficial in AD. Lastly, we delineate possible mechanisms that can work alone or in concert to ultimately lead to mitophagy impairment in neurons and may contribute to AD etiopathology.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"13 11","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mitochondrial Reactive Oxygen Species Dysregulation in Heart Failure with Preserved Ejection Fraction: A Fraction of the Whole.","authors":"Caroline Silveira Martinez, Ancheng Zheng, Qingzhong Xiao","doi":"10.3390/antiox13111330","DOIUrl":"10.3390/antiox13111330","url":null,"abstract":"<p><p>Heart failure with preserved ejection fraction (HFpEF) is a multifarious syndrome, accounting for over half of heart failure (HF) patients receiving clinical treatment. The prevalence of HFpEF is rapidly increasing in the coming decades as the global population ages. It is becoming clearer that HFpEF has a lot of different causes, which makes it challenging to find effective treatments. Currently, there are no proven treatments for people with deteriorating HF or HFpEF. Although the pathophysiologic foundations of HFpEF are complex, excessive reactive oxygen species (ROS) generation and increased oxidative stress caused by mitochondrial dysfunction seem to play a critical role in the pathogenesis of HFpEF. Emerging evidence from animal models and human myocardial tissues from failed hearts shows that mitochondrial aberrations cause a marked increase in mitochondrial ROS (mtROS) production and oxidative stress. Furthermore, studies have reported that common HF medications like beta blockers, angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, and mineralocorticoid receptor antagonists indirectly reduce the production of mtROS. Despite the harmful effects of ROS on cardiac remodeling, maintaining mitochondrial homeostasis and cardiac functions requires small amounts of ROS. In this review, we will provide an overview and discussion of the recent findings on mtROS production, its threshold for imbalance, and the subsequent dysfunction that leads to related cardiac and systemic phenotypes in the context of HFpEF. We will also focus on newly discovered cellular and molecular mechanisms underlying ROS dysregulation, current therapeutic options, and future perspectives for treating HFpEF by targeting mtROS and the associated signal molecules.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"13 11","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11591317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2024-10-31DOI: 10.3390/antiox13111331
Ileana Katerina Ioniuc, Ancuta Lupu, Felicia Dragan, Irina Tarnita, Monica Mihaela Alexoae, Violeta Streanga, Costica Mitrofan, Aye Aung Thet, Alin Horatiu Nedelcu, Delia Lidia Salaru, Stefan Lucian Burlea, Elena Cristina Mitrofan, Vasile Valeriu Lupu, Alice Nicoleta Azoicai
{"title":"Oxidative Stress and Antioxidants in Pediatric Asthma's Evolution and Management.","authors":"Ileana Katerina Ioniuc, Ancuta Lupu, Felicia Dragan, Irina Tarnita, Monica Mihaela Alexoae, Violeta Streanga, Costica Mitrofan, Aye Aung Thet, Alin Horatiu Nedelcu, Delia Lidia Salaru, Stefan Lucian Burlea, Elena Cristina Mitrofan, Vasile Valeriu Lupu, Alice Nicoleta Azoicai","doi":"10.3390/antiox13111331","DOIUrl":"10.3390/antiox13111331","url":null,"abstract":"<p><p>Within the pediatric population, bronchial asthma is one of the most prevalent chronic respiratory system diseases. The number of exacerbations, severity, and duration of symptoms all have a significant impact on children's life quality. In the last decades, the prevention and management strategies of this pathology have focused on maintaining or even increasing the pulmonary function to maximum levels in early childhood, as it has been demonstrated that functional deficits at this level occurring before school age cause pathological manifestations later, in adulthood. The epithelium of the airways and implicitly that of the lung is the first barrier against the lesions caused by pro-oxidative factors. Both oxidative and antioxidative factors can be of endogenous origin (produced by the body) or exogenous (from the environment or diet). Good functioning of antioxidant defense mechanisms from the molecular level to the tissue level, and a balance between pro-oxidative factors and anti- oxidative factors, influence the occurrence of compensatory mechanisms at the level of the respiratory epithelium, causing the delay of local responses to the stress induced by chronic inflammation (bronchial remodeling, thickening of airway smooth muscles, bronchoconstriction, bronchial hyper-reactivity). These mechanisms underlie the pathophysiological changes in asthma. Numerous studies carried out among the pediatric population inclusively have demonstrated the effectiveness of antioxidants in the prophylaxis, slowing down and preventing the progression of this pathology. This review complements the scientific articles, aiming at emphasizing the complexity of oxidative physio-pathological pathways and their importance in the occurrence, development, and therapeutic response in asthma, providing a good understanding of the relationship between oxidative and antioxidative factors, and being a source of future therapeutic strategies.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"13 11","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2024-10-31DOI: 10.3390/antiox13111336
Gi Cheol Park, Soo-Young Bang, Ji Min Kim, Sung-Chan Shin, Yong-Il Cheon, Kwang Min Kim, Hanaro Park, Eui-Suk Sung, Minhyung Lee, Jin-Choon Lee, Byung-Joo Lee
{"title":"Inhibiting Ferroptosis Prevents the Progression of Steatotic Liver Disease in Obese Mice.","authors":"Gi Cheol Park, Soo-Young Bang, Ji Min Kim, Sung-Chan Shin, Yong-Il Cheon, Kwang Min Kim, Hanaro Park, Eui-Suk Sung, Minhyung Lee, Jin-Choon Lee, Byung-Joo Lee","doi":"10.3390/antiox13111336","DOIUrl":"10.3390/antiox13111336","url":null,"abstract":"<p><p>Ferroptosis, a form of regulated cell death characterized by lipid peroxidation and iron accumulation, has been implicated in the progression of metabolic-dysfunction-associated steatohepatitis (MASH) in obesity. This study investigated the role of ferroptosis in the development of hepatic steatosis and MASH in obese mice and assessed the therapeutic potential of ferrostatin-1, a ferroptosis inhibitor. C57BL/6J wild-type (n = 8) and ob/ob mice (n = 16) were maintained on a standard chow diet. Mice were divided into three groups that included C57BL/6 (n = 8), ob/ob (n = 8), and ob/ob + ferrostatin-1 (FER) (n = 8), with the latter group receiving an intraperitoneal injection of 5 μM/kg ferrostatin three times per week for eight weeks. Following treatment, serum and tissue samples were collected for analysis. Significant hepatic steatosis and increased lipogenesis markers were observed in ob/ob mice, which were restored to baseline levels in the ob/ob + FER group treated with ferrostatin-1. Elevated oxidative stress was indicated by increased reactive oxygen species (ROS) and malondialdehyde (MDA) levels in the ob/ob group, while glutathione peroxidase 4 (GPX4) activity was significantly reduced. Ferrostatin-1 treatment decreases MDA levels and restores GPX4 activity. Additionally, ferrostatin mitigates iron overload and promotes macrophage polarization from M1 to M2, thereby reducing liver inflammation and fibrosis. Ferrostatin treatment reversed mitochondrial dysfunction in ob/ob mice. Our findings revealed that ferroptosis plays a significant role in the progression of obesity to hepatic steatosis and MASH. Inhibiting ferroptosis using ferrostatin-1 effectively improves liver histology, reduces oxidative stress, normalizes lipogenesis, and modulates macrophage polarization. This study highlights the potential of targeting ferroptosis as a therapeutic strategy for obesity-related liver diseases, warranting further investigation in clinical settings.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"13 11","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2024-10-31DOI: 10.3390/antiox13111334
Jihee Lee, Ho Sung Kim, Jeong Woo Park, Bohyun Yun, Woo Young Bang, Ki Hwan Moon, Youngwan Seo
{"title":"Exploration of New Drug Candidate Derived from Antioxidants of Korean Native Halophytes: Control of <i>Acinetobacter baumannii</i> with Antipathogenic Activity.","authors":"Jihee Lee, Ho Sung Kim, Jeong Woo Park, Bohyun Yun, Woo Young Bang, Ki Hwan Moon, Youngwan Seo","doi":"10.3390/antiox13111334","DOIUrl":"10.3390/antiox13111334","url":null,"abstract":"<p><p>The rise of antibiotic-resistant bacteria poses a significant challenge to the treatment of bacterial infections, necessitating the development of novel antibiotics or strategies to preserve the efficacy of existing ones. This study investigates the role of oxidative stress modulation in the pathogenicity of multidrug-resistant (MDR) bacterial strains, aiming to identify potential avenues for new drug design. Specifically, the anti-biofilm effects of crude extracts and fractions from seven halophyte species native to Jeju Island, South Korea, were evaluated against <i>Acinetobacter baumannii</i> ATCC 17978. Notably, the 85% aqueous methanol fraction of <i>Peucedanum japonicum</i> Thunb. (<i>Pj</i>) and the <i>n</i>-hexane fraction of <i>Lysimachia mauritiana</i> Lam. (<i>Lm</i>) demonstrated significant anti-biofilm activity. Further assessments revealed that these fractions also exhibited notable antioxidant and anti-inflammatory properties, with the <i>Pj</i> fraction showing a lifespan extension effect in the <i>Caenorhabditis elegans</i> model. These findings suggest that <i>Pj</i> and <i>Lm</i> hold promise as potential candidates for the development of new therapeutic agents targeting MDR bacteria.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"13 11","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11591331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2024-10-31DOI: 10.3390/antiox13111338
Fan Cao, Jing Chen, Zheng-Tao Lin, Han-Ying Lin, Bin Liu, Zhen-Wei Chen, Xin-Hua Ma, Yong-Hong Zhang
{"title":"Chemical Constituents from the Fruit of <i>Melia azedarach</i> and Their Anti-Inflammatory Activity.","authors":"Fan Cao, Jing Chen, Zheng-Tao Lin, Han-Ying Lin, Bin Liu, Zhen-Wei Chen, Xin-Hua Ma, Yong-Hong Zhang","doi":"10.3390/antiox13111338","DOIUrl":"10.3390/antiox13111338","url":null,"abstract":"<p><p>Phytochemical investigations of <i>Melia azedarach</i> fruits have led to the isolation of a novel tirucallane triterpenoid (<b>1</b>), four new limonoids (<b>2</b>-<b>5</b>), and four known limonoids (<b>6</b>-<b>9</b>). Their structures were clarified by comprehensive spectroscopic and spectrometric analyses. The anti-inflammatory activities of isolated compounds were assessed in vitro. Compound <b>2</b> exhibited the most potent anti-inflammatory effect, with an IC<sub>50</sub> value of 22.04 μM. Additionally, compound <b>2</b> attenuated LPS-induced reactive oxygen species (ROS) production and reduced the levels of inflammatory mediators IL-6 and TNF-<i>α</i>. A mechanistic study revealed that limonoid <b>2</b> suppresses the expression of iNOS and JAK2 and is implicated in the modulation of the NF-κB signaling cascade, which reveals its anti-inflammatory actions.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"13 11","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11591037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2024-10-31DOI: 10.3390/antiox13111333
Matthew S McCravy, Zhonghui Yang, Jaime Cyphert-Daly, Zachary R Healy, Aaron V Vose, Haein R Kim, Julia K L Walker, Robert M Tighe, Heath G Gasier, Jennifer L Ingram, Loretta G Que
{"title":"Role of Paraoxonase 2 in Airway Epithelial Response to Oxidant Stress.","authors":"Matthew S McCravy, Zhonghui Yang, Jaime Cyphert-Daly, Zachary R Healy, Aaron V Vose, Haein R Kim, Julia K L Walker, Robert M Tighe, Heath G Gasier, Jennifer L Ingram, Loretta G Que","doi":"10.3390/antiox13111333","DOIUrl":"10.3390/antiox13111333","url":null,"abstract":"<p><p>Asthma is a widespread chronic lung disease characterized by airway inflammation and hyperresponsiveness. This airway inflammation is classified by either the presence (T2-high) or absence (T2-low) of high levels of eosinophils. Because most therapies for asthma target eosinophils and related pathways, treatment options for T2-low disease are limited. New pathophysiologic targets are needed. Oxidant stress is a common feature of T2-low disease. Airway epithelial expression of the antioxidant enzyme Paraoxonase 2 (PON2) is decreased in a well-recognized population of people with T2-low asthma and people with obesity and asthma. As a potential mechanism of increased oxidant stress, we measured the role of PON2 in lung oxidant responses using an environmentally relevant in vivo murine oxidant exposure (i.e., ozone) and in vitro studies with an immortalized human airway epithelial cell line BEAS-2B. Pon2-deficient (<i>Pon2<sup>-/-</sup></i>) mice developed increased airway hyper-responsiveness compared to wild-type controls. Despite reduced alveolar macrophage influx, <i>Pon2<sup>-/-</sup></i> mice exhibited increased nitrite production. In human airway epithelial cells incubated with hydrogen peroxide, PON2 knockdown (PON2KD) decreased mitochondrial function and inner mitochondrial membrane potential. These findings suggest that PON2 functions in defending against airway epithelial oxidant stress. Further studies are needed to elucidate the mechanisms linking PON2, oxidant stress, and asthma pathogenesis.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"13 11","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11591210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2024-10-31DOI: 10.3390/antiox13111332
Jinwon Yang, Hyosun Song, Jeongjun Lee, Hunsuk Chung, Young-Sam Kwon, Kyung-Hwan Jegal, Jae-Kwang Kim, Sae-Kwang Ku
{"title":"The Effect of the Root Bark of <i>Lycium chinense</i> (Lycii Radicis Cortex) on Experimental Periodontitis and Alveolar Bone Loss in Sprague-Dawley Rats.","authors":"Jinwon Yang, Hyosun Song, Jeongjun Lee, Hunsuk Chung, Young-Sam Kwon, Kyung-Hwan Jegal, Jae-Kwang Kim, Sae-Kwang Ku","doi":"10.3390/antiox13111332","DOIUrl":"10.3390/antiox13111332","url":null,"abstract":"<p><p>Lycii Radicis Cortex (LRC), the dried root bark of <i>Lycium chinese</i> Mill., has traditionally been used as a medicinal herb in East Asia to treat fever and hyperhidrosis. In the present study, we investigated the effects of LRC extract on ligation-induced experimental periodontitis and associated alveolar bone loss in rats. Twenty-four hours after ligation placement, LRC was orally administered once daily for 10 days. Firstly, LRC administration inhibited anaerobic bacterial proliferation and inflammatory cell infiltration in gingival tissues. Additionally, LRC exhibited anti-inflammatory effects by reducing the expression of inflammatory mediators, including prostaglandin E<sub>2</sub>, interleukin-1β, and tumor necrosis factor-α. LRC treatment also downregulated mRNA expression of these inflammatory mediators in lipopolysaccharide-stimulated RAW 264.7 cells by inhibiting the mitogen-activated protein kinases and nuclear factor-κB (NF-κB) signaling pathways. Furthermore, LRC showed an antioxidant effect by decreasing the malondialdehyde level and inducible nitric oxide synthase activity in gingival tissues. Moreover, LRC effectively prevented the connective tissue degradation by inhibiting matrix metalloproteinase-8 expression and the loss of collagen-occupied areas in gingival tissues. LRC also decreased the receptor activator of NF-κB ligand/osteoprotegerin (RANKL/OPG) ratio, as well as the number and occupied areas of osteoclasts on the alveolar bone surface, thereby inhibiting alveolar bone loss. In summary, these findings suggest that LRC is a promising medicinal herb for alleviating periodontitis and related alveolar bone loss through its antimicrobial, anti-inflammatory, and antioxidant properties.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"13 11","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2024-10-31DOI: 10.3390/antiox13111335
Dimitrios G Lazaridis, Apostolos-Panagiotis Kitsios, Antonios S Koutoulis, Olga Malisova, Ioannis K Karabagias
{"title":"Fruits, Spices and Honey Phenolic Compounds: A Comprehensive Review on Their Origin, Methods of Extraction and Beneficial Health Properties.","authors":"Dimitrios G Lazaridis, Apostolos-Panagiotis Kitsios, Antonios S Koutoulis, Olga Malisova, Ioannis K Karabagias","doi":"10.3390/antiox13111335","DOIUrl":"10.3390/antiox13111335","url":null,"abstract":"<p><p>Numerous health benefits have been attributed in the last decades to the regular consumption of fruits, vegetables, herbs and spices, along with honey, in a balanced diet. In this context, the aim of the present review was to provide the literature with the most relevant studies focusing on the determination protocols of these polyphenols and other reducing agents in selected fruits (orange, lemon, grapefruit, prunus, apricot, peach, plum, sweet cherry), spices (oregano, cinnamon, clove, saffron, turmeric) and honey of different botanical origin (nectar or honeydew). In addition, the content and the extraction methods of these compounds, along with their metabolic pathway, have been critically evaluated and discussed. Results showed that all fruits, spices and honey exhibit a considerably high antioxidant activity, which is mainly owed to their phytochemical content. Therefore, a balanced diet consisting of the combination of the foods studied herein may comprise a shield against chronic and other pathophysiological disorders and may be achieved through consecutive educational programs for consumers at an international level.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"13 11","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11591358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2024-10-31DOI: 10.3390/antiox13111337
Mingyang Li, Genbao Shao
{"title":"Senataxin Attenuates DNA Damage Response Activation and Suppresses Senescence.","authors":"Mingyang Li, Genbao Shao","doi":"10.3390/antiox13111337","DOIUrl":"10.3390/antiox13111337","url":null,"abstract":"<p><p>Oxidative stress, driven by reactive oxygen species (ROS) such as hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), induces DNA double-strand breaks (DSBs) that compromise genomic integrity. The DNA Damage Response (DDR), primarily mediated by ATM and ATR kinases, is crucial for recognizing and repairing DSBs. Senataxin (SETX), a DNA/RNA helicase, is critical in resolving R-loops, with mutations in <i>SETX</i> associated with neurodegenerative diseases. This study uncovers a novel function of senataxin in modulating DDR and its impact on cellular senescence. Senataxin is shown to be crucial not only for DSB repair but also for determining cell fate under oxidative stress. <i>SETX</i> knockout cells show impaired DSB repair and prolonged ATM/ATR signaling detected by Western blotting, leading to increased senescence, as indicated by elevated β-galactosidase activity following H<sub>2</sub>O<sub>2</sub> exposure and I-PpoI-induced DSBs. Wild-type cells exhibit higher apoptosis levels compared to <i>SETX</i> knockout cells under H<sub>2</sub>O<sub>2</sub> treatment, suggesting that senataxin promotes apoptosis over senescence in oxidative stress. This indicates that senataxin plays a protective role against the accumulation of senescent cells, potentially mitigating age-related cellular decline and neurodegenerative disease progression. These findings highlight senataxin as a critical mediator in DDR pathways and a potential therapeutic target for conditions where cellular senescence contributes to disease pathology.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"13 11","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11591223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}