Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Март 1, 2024

Abstract Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family (PGC-1s), consisting of three members encompassing PGC-1α, PGC-1β, and PGC-1-related coactivator (PRC), was discovered more than a quarter-century ago. PGC-1s are essential coordinators many vital cellular events, including mitochondrial functions, oxidative stress, endoplasmic reticulum homeostasis, inflammation. Accumulating evidence has shown that implicated in diseases, such as cancers, cardiac diseases cardiovascular neurological disorders, kidney motor system metabolic disorders. Examining the upstream modulators co-activated partners identifying critical biological events modulated by downstream effectors contribute to presentation elaborate network PGC-1s. Furthermore, discussing correlation between well summarizing therapy targeting helps make individualized precise intervention methods. In this review, we summarize basic knowledge regarding molecular regulatory network, discuss physio-pathological roles human review application PGC-1s, diagnostic prognostic value several therapies pre-clinical studies, suggest directions for future investigations. This presents immense potential treatment hopefully facilitates promotion new therapeutic targets.

Язык: Английский

---

Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Окт. 14, 2024

Iron, an essential mineral in the body, is involved numerous physiological processes, making maintenance of iron homeostasis crucial for overall health. Both overload and deficiency can cause various disorders human diseases. Ferroptosis, a form cell death dependent on iron, characterized by extensive peroxidation lipids. Unlike other kinds classical unprogrammed death, ferroptosis primarily linked to disruptions metabolism, lipid peroxidation, antioxidant system imbalance. Ferroptosis regulated through transcription, translation, post-translational modifications, which affect cellular sensitivity ferroptosis. Over past decade or so, diseases have been as part their etiology, including cancers, metabolic disorders, autoimmune diseases, central nervous cardiovascular musculoskeletal Ferroptosis-related proteins become attractive targets many major that are currently incurable, some regulators shown therapeutic effects clinical trials although further validation potential needed. Therefore, in-depth analysis its molecular mechanisms may offer additional strategies prevention treatment. In this review, we discuss significance contribution etiology development along with evidence supporting targeting approach. Importantly, evaluate recent promising interventions, providing guidance future targeted treatment therapies against

Язык: Английский

---

The mechanism of ferroptosis and its related diseases

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

---

Emerging significance and therapeutic targets of ferroptosis: a potential avenue for human kidney diseases

Cell Death and Disease, Год журнала: 2023, Номер 14(9)

Опубликована: Сен. 22, 2023

Abstract Kidney diseases remain one of the leading causes human death and have placed a heavy burden on medical system. Regulated cell contributes to pathology plethora renal diseases. Recently, with in-depth studies into kidney death, new iron-dependent modality, known as ferroptosis, has been identified attracted considerable attention among researchers in pathogenesis therapeutics treat them. The majority suggest that ferroptosis plays an important role pathologies multiple diseases, such acute injury (AKI), chronic disease, carcinoma. In this review, we summarize recently regulatory molecular mechanisms discuss pathways action various describe protective effect inhibitors against especially AKI. By summarizing prominent roles different progress made studying provide directions strategies for future research summary, ferroptotic factors are potential targets therapeutic intervention alleviate targeting them may lead treatments patients

Язык: Английский

---

The role of polyamine metabolism in cellular function and physiology

AJP Cell Physiology, Год журнала: 2024, Номер 327(2), С. C341 - C356

Опубликована: Июнь 17, 2024

Polyamines are molecules with multiple amino groups that essential for cellular function. The major polyamines putrescine, spermidine, spermine, and cadaverine. important posttranscriptional regulation, autophagy, programmed cell death, proliferation, redox homeostasis, ion channel Their levels tightly controlled. High of associated proliferative pathologies such as cancer, whereas low polyamine observed in aging, elevated turnover enhances oxidative stress. Polyamine metabolism is implicated several pathophysiological processes the nervous, immune, cardiovascular systems. Currently, manipulating under investigation a potential preventive treatment pathologies, including ischemia/reperfusion injury, pulmonary hypertension, cancer. Although have been many intracellular mechanisms, our understanding these remains incomplete topic ongoing investigation. Here, we discuss regulation functions polyamines, their role physiology pathology, emphasize current gaps knowledge future research directions.

Язык: Английский

---

Desflurane Attenuates Renal Ischemia-Reperfusion Injury by Modulating ITGB1/CD9 and Reducing Oxidative Stress in Tubular Epithelial Cells

Redox Biology, Год журнала: 2025, Номер 80, С. 103490 - 103490

Опубликована: Янв. 5, 2025

Renal ischemia-reperfusion (I/R) injury triggers significant oxidative stress and inflammation, leading to tubular epithelial cell (TEC) damage. This study investigates the protective role of Desflurane (DFE) in renal I/R by modulating ITGB1/CD9 signaling pathway mitigating Single-cell RNA sequencing (scRNA-seq) transcriptome analysis identified ITGB1 as a key regulatory gene TECs during I/R. The effects DFE on expression were evaluated through vitro experiments using RT-qPCR, Western blot, TUNEL assays. A mouse model was employed assess function markers under treatment. reduced CD9 expression, resulting decreased TEC apoptosis enhanced proliferation. In vivo, DFE-treated mice exhibited improved function, with significantly lower serum creatinine blood urea nitrogen (BUN) levels. Additionally, stress, indicated malondialdehyde (MDA) myeloperoxidase (MPO) activity, alongside increased superoxide dismutase (SOD) activity. confers protection against axis reducing offering promising therapeutic strategy for kidney

Язык: Английский

---

Nanodrugs Targeting Key Factors of Ferroptosis Regulation for Enhanced Treatment of Osteoarthritis

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 22, 2025

Abstract Osteoarthritis (OA) is a globally prevalent degenerative joint disease. Recent studies highlight the role of ferroptosis in OA progression. Targeting regulation presents promising therapeutic strategy for OA; however, current research primarily focuses on single targets associated with ferroptosis. In this study, reactive oxygen species (ROS)‐responsive nanoparticle developed by linking deferasirox (DEF) and pterostilbene (PTE) thioketal incorporating cerium ions (Ce), creating Ce@D&P nanoparticles (NPs), which offer multitarget The characteristics NPs are evaluated their effects IL‐1β‐stimulated chondrocytes verified. Results show that reduce ROS levels, mitigate inflammation, chelate iron to inhibit ferroptosis, balance extracellular matrix (ECM) metabolism chondrocytes. Mechanistically, transcriptomics metabolomics analyses suggest exerted regulating oxidative stress lipid To better treat destabilization medial meniscus (DMM)‐induced mice, via intra‐articular injection delivered. results alleviate cartilage damage slow Overall, findings indicate represent drug delivery system, may be an effective treatment.

Язык: Английский

---

Roles of DNA damage in renal tubular epithelial cells injury

Frontiers in Physiology, Год журнала: 2023, Номер 14

Опубликована: Апрель 6, 2023

The prevalence of renal diseases including acute kidney injury (AKI) and chronic disease (CKD) is increasing worldwide. However, the pathogenesis most still unclear effective treatments are lacking. DNA damage related response (DDR) have been confirmed as common disease. Reactive oxygen species (ROS) induced one types involved in In recent years, several developments made field damage. Herein, we review roles tubular epithelial cell this review, conclude that focusing on may provide valuable diagnostic biomarkers treatment strategies for

Язык: Английский

---

Molecular mechanism of NR4A1/MDM2/P53 signaling pathway regulation inducing ferroptosis in renal tubular epithelial cells involved in the progression of renal ischemia-reperfusion injury

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2023, Номер 1870(2), С. 166968 - 166968

Опубликована: Ноя. 24, 2023

Язык: Английский

---

Neutrophil membrane-coated taurine nanoparticles protect against hepatic ischemia-reperfusion injury

European Journal of Pharmacology, Год журнала: 2023, Номер 949, С. 175712 - 175712

Опубликована: Апрель 11, 2023

Hepatic ischemia-reperfusion (I/R) injury is a multifactorial process caused by transient tissue hypoxia and the following reoxygenation, commonly occurring in liver transplantation hepatectomy. I/R can induce systemic inflammatory response, dysfunction, or even multiple organ failure. Although we have previously reported that taurine could attenuate acute after hepatic I/R, only tiny proportion of systemically injected reach targeted tissues. In this present study, prepared nanoparticles (Nano-taurine) coating with neutrophil membranes investigated protective effects Nano-taurine against I/R-induced underlying mechanisms. Our results showed restored function declining AST ALT levels reducing histology damage. decreased cytokines, including interleukin (IL)-6, tumor necrosis factor (TNF)-α, intercellular adhesion molecule (ICAM)-1, NLR pyrin domain containing 3 (NLRP3) apoptosis-associated speck-like protein CARD (ASC) oxidants superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), catalase (CAT) reactive oxygen species (ROS), exhibiting anti-inflammatory antioxidant properties. The expression solute carrier family 7 member 11 (SLC7A11) peroxidase 4 (GPX4) was increased, while prostaglandin-endoperoxide synthase 2 (Ptgs2) upon administration Nano-taurine, suggesting inhibiting ferroptosis may be involved mechanism during injury. These suggest therapeutic effect on inflammation, oxidative stress, ferroptosis.

Язык: Английский

---