Pexophagy and Oxidative Stress: Focus on Peroxisomal Proteins and Reactive Oxygen Species (ROS) Signaling Pathways

Antioxidants, Год журнала: 2025, Номер 14(2), С. 126 - 126

Опубликована: Янв. 23, 2025

Peroxisomes generate reactive oxygen species (ROS) and also play a role in protecting cells from the damaging effects of such radicals. Dysfunctional peroxisomes are recognized by receptors degraded selective type macroautophagy called pexophagy. Oxidative stress is one signals that activates pexophagy through multiple signaling pathways. Conversely, impaired results accumulation damaged peroxisomes, which turn leads to elevated ROS levels oxidative stress, resulting as cellular dysfunction progression diseases neurodegeneration, cancer, metabolic disorders. This review explores molecular mechanisms driving its regulation with particular focus on ROS. highlights peroxisomal proteins ROS-mediated pathways regulating In addition, emerging evidence suggests dysregulation closely linked neurological disorders, underscoring potential therapeutic target. Understanding intricate crosstalk between provides new insights into maintenance homeostasis offers promising directions for addressing disorders tightly associated stress.

Язык: Английский

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Muscle-specific PGC-1α modulates mitochondrial oxidative stress in aged sarcopenia through regulating Nrf2

Experimental Gerontology, Год журнала: 2024, Номер 193, С. 112468 - 112468

Опубликована: Май 28, 2024

Aged sarcopenia is characterized by loss of skeletal muscle mass and strength, mitochondrial dysregulation in myocyte considered as a major factor. Here, we aimed to analyze the effects peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) on reactive oxygen species (ROS) nuclear factor erythroid 2-related 2 (Nrf2) aged muscles.

Язык: Английский

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Aging-Related Sarcopenia: Metabolic Characteristics and Therapeutic Strategies

Aging and Disease, Год журнала: 2024, Номер unknown, С. 0 - 0

Опубликована: Янв. 1, 2024

The proportion of the elderly population is gradually increasing as a result medical care advances, leading to subsequent surge in geriatric diseases that significantly impact quality life and pose substantial healthcare burden. Sarcopenia, characterized by age-related decline skeletal muscle mass quality, affects considerable portion older adults, particularly elderly, can adverse outcomes such frailty, fractures, bedridden, hospitalization, even mortality. Skeletal aging accompanied underlying metabolic changes. Therefore, elucidating these profiles specific mechanisms holds promise for informing prevention treatment strategies sarcopenia. This review provides comprehensive overview key metabolites identified current clinical studies on sarcopenia their potential pathophysiological alterations activity. Besides, we examine therapeutic from perspective focused regulation.

Язык: Английский

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PGC-1α participates in regulating mitochondrial function in aged sarcopenia through effects on the Sestrin2-mediated mTORC1 pathway

Experimental Gerontology, Год журнала: 2024, Номер 190, С. 112428 - 112428

Опубликована: Апрель 11, 2024

Mitochondrial dysregulation in skeletal myocytes is considered a major factor aged sarcopenia. In this study, we aimed to study the effects of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) on Sestrin2-mediated mechanistic target rapamycin complex 1 (mTORC1) muscles.

Язык: Английский

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Transient hydroxycholesterol treatment restrains TCR signaling to promote long-term immunity

Cell chemical biology, Год журнала: 2024, Номер 31(5), С. 920 - 931.e6

Опубликована: Май 1, 2024

T cell receptor (TCR) plays a fundamental role in adaptive immunity, and TCR-T therapy holds great promise for treating solid tumors other diseases. However, there is noticeable absence of chemical tools tuning TCR activity. In our study, we screened natural sterols their regulatory effects on function identified 7-alpha-hydroxycholesterol (7a-HC) as potent inhibitor signaling. Mechanistically, 7a-HC promoted membrane binding CD3ε cytoplasmic domain, crucial signaling component the TCR-CD3 complex, through alterations physicochemical properties. Enhanced impeded condensation between key kinase Lck, thereby inhibiting Lck-mediated phosphorylation. Transient treatments cells with resulted reduced strength, increased memory populations, superior long-term antitumor functions. This study unveils regulation signaling, which can be exploited to enhance efficacy therapy.

Язык: Английский

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Cytoprotective effects of α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, oleic acid and α-tocopherol on 7-ketocholesterol – Induced oxiapoptophagy: Major roles of PI3-K / PDK-1 / Akt signaling pathway and glutathione peroxidase activity in cell rescue

Current Research in Toxicology, Год журнала: 2024, Номер 6, С. 100153 - 100153

Опубликована: Янв. 1, 2024

On murine N2a cells, 7-ketocholesterol induced an oxiapotophagic mode of cell death characterized by oxidative stress (reactive oxygen species overproduction on whole cells and at the mitochondrial level; lipid peroxidation), apoptosis induction (caspase-9, −3 −7 cleavage, PARP degradation) autophagy (increased ratio LC3-II / LC3-I). Oxidative was strongly attenuated diphenyleneiodonium chloride which inhibits NAD(P)H oxidase. Mitochondrial peroxisomal morphological functional changes were also observed. Down regulation PDK1 Akt signaling pathways as well GSK3 Mcl-1 Nrf2 simultaneously observed in 7-ketocholesterol-induced oxiapoptophagy. These events prevented α-linolenic acid, eicosapentaenoic docosahexaenoic oleic acid α-tocopherol. The inhibition cytoprotection LY-294002, a PI3-K inhibitor, demonstrated essential role rescue. rupture oxiapoptophagy associated with important modifications glutathione peroxidase, superoxide dismutase catalase activities peroxidase-1, dismutase-1 level expression. counteracted mercaptosuccinic peroxidase showed this enzyme Altogether, our data support that reactivation α-tocopherol are to prevent 7KC-induced

Язык: Английский

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The association between non‑high‑density lipoprotein cholesterol to high‑density lipoprotein cholesterol ratio (NHHR) and low muscle mass in adults aged 20–59: a population-based study in the United States

Lipids in Health and Disease, Год журнала: 2024, Номер 23(1)

Опубликована: Авг. 28, 2024

The ratio between non-high-density lipoprotein cholesterol and high-density (NHHR) is a reliable marker for assessing the risk linked to lipid metabolism disorders. Sarcopenia, characterized by age-related loss of muscle mass strength/function, includes assessment mass, strength, muscle-specific strength. However, research into NHHR's relationship with low remains unexplored.

Язык: Английский

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Lipid peroxidation and sarcopenia: molecular mechanisms and potential therapeutic approaches

Frontiers in Medicine, Год журнала: 2025, Номер 12

Опубликована: Фев. 3, 2025

Sarcopenia is an age-related condition characterized by the progressive loss of skeletal muscle mass and strength. With global aging population, its incidence rapidly increasing. Lipid peroxidation a critical biochemical process that generates reactive oxygen species (ROS), leading to destruction cell structure function. It plays pivotal role in onset progression sarcopenia. This review summarizes mechanisms which lipid contributes sarcopenia, with focus on regulatory effects membrane damage, mitochondrial dysfunction, death. In addition, we discuss protective antioxidant factors such as GPX4 (glutathione peroxidase 4) peptides like SS mitigating delaying Finally, potential various strategies, including natural compounds, supplements, extracts, lifestyle interventions, inhibiting promoting health explored.

Язык: Английский

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Impact of myosteatosis on prognosis in multiple myeloma patients: A subgroup analysis of 182 cases and development of a nomogram

Journal of bone oncology, Год журнала: 2025, Номер 51, С. 100670 - 100670

Опубликована: Март 11, 2025

This study aims to explore the prognostic value of myosteatosis in multiple myeloma (MM) and analyze factors influencing myosteatosis. A retrospective analysis was conducted on 182 patients treated for MM at our institution from 2009 2020 who underwent MRI examinations. The fatty infiltration rate (FIR) erector spinae multifidus muscles L3 level measured assess degree Patients were grouped based fracture presence median FIR, group differences compared, with P < 0.05 considered statistically significant. Survival fractures used as indicators, regression performed determine impact FIR these outcomes patients. analyzed, relationship between prognosis further analyzed within its sensitive subgroups. Finally, a nomogram established validated. Significant observed non-fracture groups lactate dehydrogenase, serum phosphorus, visual analogue scale, oswestry disability index (P 0.05). When (28.89 %), there significant age, sex, body mass (BMI), red blood cell (RBC) count, hemoglobin, hematocrit, albumin, index, incidence Univariate COX indicated that had no survival (HR = 0.999, 0.852), log-rank test 0.11 when by cut-off 33.67 %. Multivariate logistic is an independent predictor (OR 1.054, 0.000). linear revealed RBC BMI are not grouped, FIR's prediction showed interaction or > In subgroups ≥ 25 kg/m2 count 3.68 × 10^12/L, lost predictive significance fractures. model C-index 0.777, calibration curve, decision curve analysis, clinical all validated effectiveness. Myosteatosis characterized reliable but effective predicting closely related back pain functional impairment. significantly associated BMI.

Язык: Английский

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The Link Between Oxysterols and Gut Microbiota in the Co-Dysfunction of Cognition and Muscle

Nutrients, Год журнала: 2025, Номер 17(7), С. 1277 - 1277

Опубликована: Апрель 6, 2025

Background/Objectives: Alterations of oxysterols and gut microbiota have been recognized as indicators affecting mild cognitive impairment (MCI) sarcopenia, respectively, whereas their association with co-dysfunction has not investigated. Methods: In this study, a total 1035 individuals were divided into Control (n = 264), MCI 435), possible sarcopenia (MPS, n 336) groups. Cognition muscle indexes, serum oxysterols, measured. Spearman's rank coefficients calculated to determine correlations. Results: Performances global multidimensional tests was successively worse in the Control, MCI, MPS Longer duration five-time chair stand test, lower 6-meter walk speed, handgrip strength observed group, along increased 27-hydroxycholesterol (27-OHC) 5α,6α-epoxycholesterol decreased 5α-Cholest-8(14)-ene-3β,15α-diol (15-HC). Higher concentrations amyloid precursor protein (APP), neurofilament, C-terminal agrin fragment (CAF) discovered The α-diversity group remarkably decreased, followed by shifted abundance microbial taxa, such Alistipes Rikenellaceae. Multiple significant correlations found between cognition indexes oxysterols. Conclusions: Our study indicates that are prominently involved muscle.

Язык: Английский

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