Chemico-Biological Interactions, Год журнала: 2024, Номер 390, С. 110890 - 110890
Опубликована: Янв. 24, 2024
Язык: Английский
Frontiers in Immunology, Год журнала: 2022, Номер 13
Опубликована: Июль 22, 2022
Quercetin, a naturally non-toxic flavonoid within the safe dose range with antioxidant, anti-apoptotic and anti-inflammatory properties, plays an important role in treatment of aging-related diseases. Sirtuin 1 (SIRT1), member NAD+-dependent deacetylase enzyme family, is extensively explored as potential therapeutic target for attenuating aging-induced disorders. SIRT1 possess beneficial effects against diseases such Alzheimer's disease (AD), Parkinson's (PD), Huntington's (HD), Depression, Osteoporosis, Myocardial ischemia (M/I) reperfusion (MI/R), Atherosclerosis (AS), Diabetes. Previous studies have reported that aging increases tissue susceptibility, whereas, regulates cellular senescence multiple processes, including SIRT1/Keap1/Nrf2/HO-1 SIRTI/PI3K/Akt/GSK-3β mediated oxidative stress, SIRT1/NF-κB SIRT1/NLRP3 regulated inflammatory response, SIRT1/PGC1α/eIF2α/ATF4/CHOP SIRT1/PKD1/CREB controlled phosphorylation, SIRT1-PINK1-Parkin mitochondrial damage, SIRT1/FoxO autophagy, SIRT1/FoxG1/CREB/BDNF/Trkβ-catenin neuroprotective effects. In this review, we summarized improvement attenuation effect quercetin on relationship between relevant signaling pathways by SIRT1. Moreover, functional regulation markers function, autophagy apoptosis through was discussed. Finally, prospects extracellular vesicles (EVs) loading delivery, SIRT1-mediated EVs signal carriers treating diseases, well discussed ferroptosis alleviation to protect via activating Generally, may serve promising inhibiting reducing responses, restoring dysfunction.
Язык: Английский
Процитировано
207
Biomedicine & Pharmacotherapy, Год журнала: 2022, Номер 154, С. 113572 - 113572
Опубликована: Авг. 18, 2022
The present study aimed to investigate whether dexmedetomidine (Dex) exerts cardioprotection effect through inhibiting ferroptosis. Myocardial ischemia/reperfusion injury (MIRI) was induced in Sprague-Dawley rats Langendorff preparation. hemodynamic parameters were recorded. Triphenyltetrazolium chloride (TTC) staining used determine infarct size. In the vitro study, model of hypoxia/reoxygenation (HR) established H9c2 cells. Cell viability and apoptosis detected using cell counting kit 8 (CCK-8), AV/PI dual respectively. Lipid peroxidation as measured by fluorescence fatty acid analog C11-BODIPY581/591 probe intracellular ferrous iron levels Phen Green SK (PGSK) probe, whereas immunofluorescence transmission electron microscopy also examine Protein investigated Western blot. interactions AMPK/GSK-3β signaling with Nrf2 assessed AMPK inhibition GSK-3β overexpression. Our findings indicated that Dex significantly alleviated myocardial infarction, improved heart function, decreased HR-induced accumulation Fe2+ lipid cardiomyocytes. increased expression Nrf2, SLC7A11, GPX4. However, ML385 blunted protective HR-treated Inhibition a specific inhibitor or siRNA phosphorylation Dex. Overexpression resulted lower nuclear depression enhanced expressions Nrf2. conclusion, protects hearts against MIRI-induced ferroptosis via activation pathway.
Язык: Английский
Процитировано
165
Cell Communication and Signaling, Год журнала: 2023, Номер 21(1)
Опубликована: Март 14, 2023
Doxorubicin (DOX) is a powerful and commonly used chemotherapeutic drug, alone or in combination variety of cancers, while it has been found to cause serious cardiac side effects clinical application. More more researchers are trying explore the molecular mechanisms DOX-induced cardiomyopathy (DIC), which oxidative stress inflammation considered play significant role. This review summarizes signaling pathways related DIC compounds that exert cardioprotective by acting on relevant pathways, including role Nrf2/Keap1/ARE, Sirt1/p66Shc, Sirt1/PPAR/PGC-1α NOS, NOX, Fe2+ stress, as well NLRP3/caspase-1/GSDMD, HMGB1/TLR4/MAPKs/NF-κB, mTOR/TFEB/NF-κB inflammation. Hence, we attempt explain terms inflammation, provide theoretical basis new idea for further drug research reducing DIC. Video Abstract.
Язык: Английский
Процитировано
108
Nature Reviews Cardiology, Год журнала: 2023, Номер 20(7), С. 443 - 462
Опубликована: Янв. 6, 2023
Язык: Английский
Процитировано
95
Cell Death and Disease, Год журнала: 2023, Номер 14(2)
Опубликована: Фев. 16, 2023
Abstract The glutathione (GSH) system is considered to be one of the most powerful endogenous antioxidant systems in cardiovascular due its key contribution detoxifying xenobiotics and scavenging overreactive oxygen species (ROS). Numerous investigations have suggested that disruption GSH a critical element pathogenesis myocardial injury. Meanwhile, newly proposed type cell death, ferroptosis, has been demonstrated closely related system, which affects process outcome Moreover, facing various pathological challenges, mammalian heart, possesses high levels mitochondria weak capacity, susceptible oxidant production oxidative damage. Therefore, targeted enhancement along with prevention ferroptosis myocardium promising therapeutic strategy. In this review, we first systematically describe physiological functions anabolism as well effects on cardiac Then, discuss relationship between comprehensive summary activation strategies presented, where mainly identify several herbal monomers, may provide valuable guidelines for exploration new approaches.
Язык: Английский
Процитировано
91
Journal of Agricultural and Food Chemistry, Год журнала: 2023, Номер 71(6), С. 2745 - 2761
Опубликована: Янв. 31, 2023
Type 2 diabetic osteoporosis (T2DOP) is a chronic bone metabolic disease. Compared with traditional menopausal osteoporosis, the long-term high glucose (HG) microenvironment increases patients' risk of fracture and osteonecrosis. We were accumulating evidence that implicated ferroptosis as pivotal mechanism glucolipotoxicity-mediated death osteocytes osteoblast, novel form programmed cell resulting from uncontrolled lipid peroxidation depending on iron. Vitamin K2 (VK2), fat-soluble vitamin, clinically applied to prevent improve coagulation. This study aimed clarify role VK2 in HG-mediated ferroptosis. established mouse T2DOP model by intraperitoneal injection streptozotocin solution high-fat high-sugar diet. also cultured marrow mesenchymal stem cells (BMSCs) HG simulate environment vitro. Based our data, inhibited loss ferroptosis, latter manifested decreased levels mitochondrial reactive oxygen species, peroxidation, malondialdehyde increased glutathione In addition, treatment was capable restoring mass strengthening expression SIRT1, GPX4, osteogenic markers distal femurs. As for further exploration, we found could activate AMPK/SIRT1 signaling, knockdown SIRT1 siRNA prevented VK2-mediated positive effect HG-cultured BMSCs. Summarily, ameliorate through activation signaling pathway inhibit
Язык: Английский
Процитировано
59
Molecular Biomedicine, Год журнала: 2023, Номер 4(1)
Опубликована: Окт. 16, 2023
Abstract Ferroptosis, a regulated form of cellular death characterized by the iron-mediated accumulation lipid peroxides, provides novel avenue for delving into intersection metabolism, oxidative stress, and disease pathology. We have witnessed mounting fascination with ferroptosis, attributed to its pivotal roles across diverse physiological pathological conditions including developmental processes, metabolic dynamics, oncogenic pathways, neurodegenerative cascades, traumatic tissue injuries. By unraveling intricate underpinnings molecular machinery, contributors, signaling conduits, regulatory networks governing researchers aim bridge gap between intricacies this unique mode multifaceted implications health disease. In light rapidly advancing landscape ferroptosis research, we present comprehensive review aiming at extensive in origins progress human diseases. This concludes careful analysis potential treatment approaches carefully designed either inhibit or promote ferroptosis. Additionally, succinctly summarized therapeutic targets compounds that hold promise targeting within various facet underscores burgeoning possibilities manipulating as strategy. summary, enriched insights both investigators practitioners, while fostering an elevated comprehension latent translational utilities. revealing basic processes investigating possibilities, crucial resource scientists medical aiding deep understanding effects situations.
Язык: Английский
Процитировано
59
Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 174, С. 116512 - 116512
Опубликована: Апрель 3, 2024
GPX4 (Glutathione peroxidase 4) serves as a crucial intracellular regulatory factor, participating in various physiological processes and playing significant role maintaining the redox homeostasis within body. Ferroptosis, form of iron-dependent non-apoptotic cell death, has gained considerable attention recent years due to its involvement multiple pathological processes. is closely associated with ferroptosis functions primary inhibitor this process. Together, contribute pathophysiology several diseases, including sepsis, nervous system ischemia reperfusion injury, cardiovascular cancer. This review comprehensively explores roles impacts development progression these aim providing insights for identifying potential therapeutic strategies future.
Язык: Английский
Процитировано
51
Cell Death Discovery, Год журнала: 2023, Номер 9(1)
Опубликована: Июль 26, 2023
Abstract Being a broad-spectrum anticancer drug, doxorubicin is indispensable for clinical treatment. Unexpectedly, its cardiotoxic side effects have proven to be formidable obstacle. Numerous studies are currently devoted elucidating the pathological mechanisms underlying doxorubicin-induced cardiotoxicity. Nrf2 has always played crucial role in oxidative stress, but numerous demonstrated that it also plays vital part like cell death and inflammation. on associated with cardiotoxicity demonstrate this. Several drugs, natural synthetic compounds, as well small molecule RNAs been prevent by activating Nrf2. Consequently, this study emphasizes introduction of Nrf2, discusses cardiotoxicity, concludes summary therapeutic modalities targeting ameliorate highlighting potential value
Язык: Английский
Процитировано
41
Redox Biology, Год журнала: 2024, Номер 69, С. 103030 - 103030
Опубликована: Янв. 3, 2024
Ferroptosis is a type of programmed cell death resulting from iron overload-dependent lipid peroxidation, and could be promoted by activating transcription factor 3 (ATF3). SIRT1 an enzyme accounting for removing acetylated lysine residues target proteins consuming NAD+, but its role remains elusive in ferroptosis ATF3. In this study, we found was activated during the process RSL3-induced glioma ferroptosis. Moreover, aggravated activator SRT2183, suppressed SIRT inhibitor EX527 or when silenced with siRNA. These indicated sensitized cells to Furthermore, expressional upregulation nuclear translocation Silence ATF3 siRNA attenuated increases ferrous downregulation SLC7A11 GPX4 depletion cysteine GSH. Thus, inducting activation. Mechanistically, activation reinforced decline NAD+ FK866 that inhibit NAD + synthesis via salvage pathway, intracellular maintained at higher level supplement exogenous NAD+. Notably, caused RSL3 enhanced further inhibited EX527. consumption Finally, inducing reactive oxygen species-dependent AROS. Together, our study revealed AROS sensitizes ATF3-dependent inhibition GPX4.
Язык: Английский
Процитировано
21