Antioxidants & redox signaling最新文献

{"title":"Succinate Activates Uncoupling Protein 2 to Suppress Neuroinflammation and Confer Protection Following Intracerebral Hemorrhage.","authors":"Yecheng Wang, Caiyun Huang, Xiaoying Wang, Rong Cheng, Xue Li, Jiahao Wang, Lu Zhang, Fuhao Li, Hao Wang, Xinyu Li, Yi Li, Yiqing Xia, Jian Cheng, Xiaofan Pan, Jia Jia, Guo-Dong Xiao","doi":"10.1089/ars.2024.0573","DOIUrl":"10.1089/ars.2024.0573","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Succinate, a metabolite in the tricarboxylic acid cycle, is increasingly recognized to play essential roles in inflammation by functioning either as an intracellular or extracellular signaling molecule. However, the role and mechanisms of succinate in inflammation remain elusive. Here, we investigated the mechanism underlying the effects of succinate on neuroinflammation in intracerebral hemorrhage (ICH) models. <b><i>Results:</i></b> We unexpectedly found that succinate robustly inhibited neuroinflammation and conferred protection following ICH. Mechanistically, the oxidation of succinate by succinate dehydrogenase (SDH) drove reverse electron transport (RET) at mitochondrial complex I, leading to mitochondrial superoxide production in microglia. Complex I-derived superoxides, in turn, activated uncoupling protein 2 (UCP2). By using mice with specific deletion of UCP2 in microglia/macrophages, we showed that UCP2 was needed for succinate to inhibit neuroinflammation, confer protection, and activate downstream 5'-adenosine monophosphate-activated protein kinase (AMPK) following ICH. Moreover, knockdown of SDH, complex I, or AMPK abolished the therapeutic effects of succinate following ICH. <b><i>Innovation and Conclusion:</i></b> We provide evidence that driving complex I RET to activate UCP2 is a novel mechanism of succinate-mediated intracellular signaling and a mechanism underlying the inhibition of neuroinflammation by succinate.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial Reactive Oxygen Species: Key Players in Cardiovascular Health and Disease.","authors":"Siobhan M Craige, Gaganpreet Kaur, Jacob M Bond, Amada D Caliz, Shashi Kant, John F Keaney","doi":"10.1089/ars.2024.0706","DOIUrl":"10.1089/ars.2024.0706","url":null,"abstract":"<p><p><b><i>Significance:</i></b> Endothelial cells (ECs) line the entire vasculature system and serve as both barriers and facilitators of intra- and interorgan communication. Positioned to rapidly sense internal and external stressors, ECs dynamically adjust their functionality. Endothelial dysfunction occurs when the ability of ECs to react to stressors is impaired, which precedes many cardiovascular diseases (CVDs). While EC reactive oxygen species (ROS) have historically been implicated as mediators of endothelial dysfunction, more recent studies highlight the central role of ROS in physiological endothelial signaling. <b><i>Recent Advances:</i></b> New evidence has uncovered that EC ROS are fundamental in determining how ECs interact with their environment and respond to stress. EC ROS levels are mediated by external factors such as diet and pathogens, as well as inherent characteristics, including sex and location. Changes in EC ROS impact EC function, leading to changes in metabolism, cell communication, and potentially disrupted signaling in CVDs. <b><i>Critical Issues:</i></b> Current endothelial biology concepts integrate the dual nature of ROS, emphasizing the importance of EC ROS in physiological stress adaptation and their contribution to CVDs. Understanding the discrete, localized signaling of EC ROS will be critical in preventing adverse cardiovascular outcomes. <b><i>Future Directions:</i></b> Exploring how the EC ROS environment alters EC function and cross-cellular communication is critical. Considering the inherent heterogeneity among EC populations and understanding how EC ROS contribute to this diversity and the role of sexual dimorphism in the EC ROS environment will be fundamental for developing new effective cardiovascular treatment strategies.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"H₂S Donor SPRC Ameliorates Cardiac Aging by Suppression of JMJD3, a Histone Demethylase.","authors":"Sha Li, Qixiu Li, Hong Xiang, Chenye Wang, Qi Zhu, Danping Ruan, Yi Zhun Zhu, Yicheng Mao","doi":"10.1089/ars.2024.0605","DOIUrl":"10.1089/ars.2024.0605","url":null,"abstract":"<p><p><b><i>Aims:</i></b> S-propargyl-cysteine (SPRC) is an endogenous hydrogen sulfide (H₂S) donor obtained by modifying the structure of S-allyl cysteine in garlic. This study aims to investigate the effect of SPRC on mitigating cardiac aging and the involvement of jumonji domain-containing protein 3 (JMJD3), a histone demethylase, which represents the primary risk factor in major aging related diseases, in this process, elucidating the preliminary mechanism through which SPRC regulation of JMJD3 occurs. <b><i>Results:</i></b> <i>In vitro</i>, SPRC mitigated the elevated levels of reactive oxygen species, senescence-associated β-galactosidase, p53, and p21, reversing the decline in mitochondrial membrane potential, which represented a reduction in cellular senescence. <i>In vivo</i>, SPRC improved Dox-induced cardiac pathological structure and function. Overexpression of JMJD3 accelerated cardiomyocytes and cardiac senescence, whereas its knockdown <i>in vitro</i> reduced the senescence phenotype. The potential binding site of the upstream transcription factor of JMJD3, sheared X box binding protein 1 (XBP1s), was determined using online software. SPRC promoted the expression of cystathionine γ-lyase (CSE), which subsequently inhibited the IRE1α/XBP1s signaling pathway and decreased JMJD3 expression. <b><i>Innovations:</i></b> This study is the first to establish JMJD3 as a crucial regulator of cardiac aging. SPRC can alleviate cardiac aging by upregulating CSE and inhibiting endoplasmic reticulum stress pathways, which in turn suppress JMJD3 expression. <b><i>Conclusions:</i></b> JMJD3 plays an essential role in cardiac aging regulation, whereas SPRC can suppress the expression of JMJD3 by upregulating CSE, thus delaying cardiac aging, which suggests that SPRC may serve as an aging protective agent, and pharmacological targeting of JMJD3 may also be a promising therapeutic approach in age-related heart diseases.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of Mitochondrial Quality Control of Intestinal Stem Cells in Homeostasis and Diseases.","authors":"Xudan Lei, Zhenni Xu, Yujun Huang, Lingxiao Huang, Jinyi Lang, Mingyue Qu, Dengqun Liu","doi":"10.1089/ars.2023.0489","DOIUrl":"10.1089/ars.2023.0489","url":null,"abstract":"<p><p><b><i>Significance:</i></b> Intestinal stem cells (ISCs) are crucial for the continuous renewal and regeneration of the small intestinal epithelium. ISC fate decisions are strictly controlled by metabolism. Mitochondria act as the central hubs of energetic metabolism and dynamically remodel their morphology to perform required metabolic functions. Mitochondrial dysfunction is closely associated with a variety of gastrointestinal diseases. <b><i>Recent Advances:</i></b> In recent years, several studies have reported that mitochondria are potential therapeutic targets for regulating ISC function to alleviate intestinal diseases. However, how mitochondrial quality control mediates ISCs under physiological conditions and protects against intestinal injury remains to be comprehensively reviewed. <b><i>Critical Issues:</i></b> In this review, we summarize the available studies about how mitochondrial metabolism, redox state, dynamics, autophagy, and proteostasis impact ISC proliferation, differentiation, and regeneration, respectively. <b><i>Future Directions:</i></b> We propose that remodeling the function of mitochondria in ISCs may be a promising potential future direction for the treatment of intestinal diseases. This review may provide new strategies for therapeutically targeting the mitochondria of ISCs in intestinal diseases.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asperuloside as a Novel NRF2 Activator to Ameliorate Endothelial Dysfunction in High Fat Diet-Induced Obese Mice.","authors":"Chufeng He, Ruiwen Zhu, Lei He, Chui Yiu Bamboo Chook, Huixian Li, Fung Ping Leung, Gary Tse, Zhen-Yu Chen, Yu Huang, Wing Tak Wong","doi":"10.1089/ars.2024.0593","DOIUrl":"10.1089/ars.2024.0593","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Current treatments are inadequate in alleviating obesity-associated vascular diseases. The development of effective therapies to ameliorate endothelial dysfunction and attenuate oxidative stress is of utmost importance. Asperuloside (ASP), a bioactive compound extracted from <i>Eucommia species</i>, exhibits antiobesity properties. However, the effects of ASP on vasculopathy have not been investigated. Therefore, the effects of ASP on vascular dysfunction and related mechanisms were elucidated. <b><i>Results:</i></b> ASP significantly reversed the impaired endothelium-dependent relaxations (EDRs) in obese mice and interleukin (IL)-1β-treated aortas. ASP suppressed endothelial activation in obese mice aortas and IL-1β-treated endothelial cells. ASP attenuated oxidative stress, scavenged mitochondrial reactive oxygen species (ROS), and upregulated heme oxygenase-1 (HO-1) expression in endothelium, independent of its anti-inflammatory properties. HO-1 knockdown diminished the protective effects of ASP against impaired EDRs, ROS overproduction, and endothelial activation. Endothelial cell-specific nuclear factor erythroid 2-related factor 2 (Nrf2) knockdown eliminated the ASP-mediated vascular protective effects and endothelial HO-1 upregulation, emphasizing that ASP improves endothelial function by activating Nrf2/HO-1 signaling. ASP facilitated Nrf2 nuclear translocation and the direct binding of Nrf2 to antioxidant response element, thereby enhancing HO-1 transcription and scavenging ROS. The cellular thermal shift assay results provide the first experimental characterization of the direct binding of ASP to Nrf2. <b><i>Conclusions:</i></b> These findings demonstrate that ASP ameliorates obesity-associated endothelial dysfunction by activating Nrf2/HO-1 signaling and thereby maintaining redox hemostasis, suggesting its potential as a novel Nrf2-targeted therapeutic agent and dietary supplement for vasculopathy.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"M6A RNA Methylation-Mediated TUG1 Stability Maintains Mitochondrial Homeostasis during Kidney Aging by Epigenetically Regulating PGC1-α Expression.","authors":"Yonghong Zhu, Bowen Yang, Suyun Chen, Guanqing Chen, Xiaobian Zeng, Hui Min, Li Xu","doi":"10.1089/ars.2024.0631","DOIUrl":"10.1089/ars.2024.0631","url":null,"abstract":"","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nattokinase's Neuroprotective Mechanisms in Ischemic Stroke: Targeting Inflammation, Oxidative Stress, and Coagulation.","authors":"Xin-Ying Yang, Sheng-Lin Wang, Wen-Chi Xue, Yu-Peng Zhang, Liang-Liang Li, Zhao-Hu Luo, Feng-Jiao Zhang","doi":"10.1089/ars.2023.0527","DOIUrl":"10.1089/ars.2023.0527","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Nattokinase (NK), a potent serine endopeptidase, has exhibited a variety of pharmacological effects, including thrombolysis, anti-inflammation, and antioxidative stress. Building on previous research highlighting NK's promise in nerve regeneration, our study investigated whether NK exerted protective effects in transient middle cerebral artery occlusion (tMCAO)-induced cerebral ischemia-reperfusion injury and the underlying mechanisms. <b><i>Results:</i></b> The rats were administered NK (5000, 10000, 20000 FU/kg, i.g., 7 days before surgery, once daily). We showed that NK treatment dose dependently reduced the infarction volume and improved neurological symptoms, decreased the proinflammatory and coagulation cytokines levels, and attenuated reactive oxygen species (ROS) in the infarcted area of tMCAO rats. We also found that NK could exert neuroprotective effects in a variety of vitro models, including the microglia inflammation model and neuronal oxygen-glucose deprivation/reperfusion (OGD/R) model. Notably, NK effectively countered OGD/R-induced neuron death, modulating diverse pathways, including autophagy, apoptosis, PARP-dependent death, and endoplasmic reticulum stress. Furthermore, the neuroprotection of NK was blocked by phenylmethylsulfonyl fluoride (PMSF), a serine endopeptidase inhibitor. We revealed that heat-inactive NK was unable to protect against tMCAO injury and other vitro models, suggesting NK attenuated ischemic injury by its enzymatic activity. We conducted a proteomic analysis and found inflammation and coagulation were involved in the occurrence of tMCAO model and in the therapeutic effect of NK. <b><i>Innovation and Conclusion:</i></b> In conclusion, these data demonstrated that NK had multifaceted neuroprotection in ischemic brain injury, and the therapeutic effect of NK was related with serine endopeptidase activity.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pleiotropic Regulation of PGC-1α in Tumor Initiation and Progression.","authors":"Yan Zhang, Huakan Zhao, Yongsheng Li","doi":"10.1089/ars.2023.0506","DOIUrl":"10.1089/ars.2023.0506","url":null,"abstract":"<p><p><b><i>Significance:</i></b> Mitochondria are recognized as a central metabolic hub with bioenergetic, biosynthetic, and signaling functions that tightly control key cellular processes. As a crucial component of mitochondrial biogenesis, peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) is involved in regulating various metabolic pathways, including energy metabolism and reactive oxygen species homeostasis. <b><i>Recent Advances:</i></b> Recent studies have highlighted the significant role of PGC-1α in tumorigenesis, cancer progression, and treatment resistance. However, PGC-1α exhibits pleiotropic effects in different cancer types, necessitating a more comprehensive and thorough understanding. <b><i>Critical Issues:</i></b> In this review, we discuss the structure and regulatory mechanisms of PGC-1α, analyze its cellular and metabolic functions, explore its impact on tumorigenesis, and propose potential strategies for targeting PGC-1α. <b>Future Directions</b>: The targeted adjustment of PGC-1α based on the metabolic preferences of different cancer types could offer a hopeful therapeutic approach for both preventing and treating tumors. <i>Antioxid. Redox Signal.</i> 41, 557-572.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"557-572"},"PeriodicalIF":5.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141070198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nicotinamide Adenine Dinucleotide Precursor Supplementation Modulates Neurite Complexity and Survival in Motor Neurons from Amyotrophic Lateral Sclerosis Models.","authors":"Haylee L Hamilton, Mahbuba Akther, Shaheer Anis, Christopher B Colwell, Marcelo R Vargas, Mariana Pehar","doi":"10.1089/ars.2023.0360","DOIUrl":"10.1089/ars.2023.0360","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Increasing nicotinamide adenine dinucleotide (NAD⁺) availability has been proposed as a therapeutic approach to prevent neurodegeneration in amyotrophic lateral sclerosis (ALS). Accordingly, NAD⁺ precursor supplementation appears to exert neuroprotective effects in ALS patients and mouse models. The mechanisms mediating neuroprotection remain uncertain but could involve changes in multiple cell types. We investigated a potential direct effect of the NAD⁺ precursor nicotinamide mononucleotide (NMN) on the health of cultured induced pluripotent stem cell (iPSC)-derived human motor neurons and in motor neurons isolated from two ALS mouse models, that is, mice overexpressing wild-type transactive response DNA binding protein-43 (TDP-43) or the ALS-linked human superoxide dismutase 1 with the G93A mutation (hSOD1^G93A). <b><i>Results:</i></b> NMN treatment increased the complexity of neuronal processes in motor neurons isolated from both mouse models and in iPSC-derived human motor neurons. In addition, NMN prevented neuronal death induced by trophic factor deprivation. In mouse and human motor neurons expressing ALS-linked mutant superoxide dismutase 1, NMN induced an increase in glutathione levels, but this effect was not observed in nontransgenic or TDP-43 overexpressing motor neurons. In contrast, NMN treatment normalized the TDP-43 cytoplasmic mislocalization induced by its overexpression. <b><i>Innovation:</i></b> NMN can directly act on motor neurons to increase the growth and complexity of neuronal processes and prevent the death induced by trophic factor deprivation. <b><i>Conclusion:</i></b> Our results support a direct beneficial effect of NAD⁺ precursor supplementation on the maintenance of the neuritic arbor in motor neurons. Importantly, this was observed in motor neurons isolated from two different ALS models, with and without involvement of TDP-43 pathology, supporting its therapeutic potential in sporadic and familial ALS. <i>Antioxid. Redox Signal.</i> 41, 573-589.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"573-589"},"PeriodicalIF":5.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140179238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does NLRP1 Inflammasome Activation in Immune Cells in Kidney Transplantation Relate with Donor Organ Age?","authors":"Juan Miguel Suarez-Rivero, Juan López-Pérez, Antonio Astorga-Gamaza, Inés Muela-Zarzuela, Raquel de la Varga-Martínez, Aurora Aguilera, Teresa Garcia, Auxiliadora Mazuecos, Mario D Cordero","doi":"10.1089/ars.2024.0588","DOIUrl":"10.1089/ars.2024.0588","url":null,"abstract":"","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"479-487"},"PeriodicalIF":5.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140142677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}