New insights into pulmonary arterial hypertension: interaction between PANoptosis and perivascular inflammatory responses

APOPTOSIS, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 20, 2025

Language: Английский

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Zinc Alleviates Diabetic Muscle Atrophy via Modulation of the SIRT1/FoxO1 Autophagy Pathway Through GPR39

Journal of Cachexia Sarcopenia and Muscle, Journal Year: 2025, Volume and Issue: 16(2)

Published: March 3, 2025

Muscle atrophy is a severe complication of diabetes, with autophagy playing critical role in its progression. Zinc has been shown to alleviate hyperglycaemia and several diabetes-related complications, but direct mediating diabetic muscle remains unclear. This study explores the potential zinc pathogenesis atrophy. In vivo, C57BL/6J mice were induced diabetes by streptozotocin (STZ) treated ZnSO₄ (25 mg/kg/day) for six weeks. Gastrocnemius muscles collected histological analysis, including transmission electron microscopy (TEM). Serum levels measured ICP-MS. Protein expression was evaluated using immunofluorescence (IF), immunohistochemistry (IHC) Western blotting (WB). Bioinformatics analysis used identify key genes associated vitro, high-glucose-induced C2C12 cell model established received ZnSO₄, rapamycin, SRT1720, TC-G-1008, or GPR39-CRISPR Cas9 intervention. Autophagy observed TEM, protein assessed IF WB. Intracellular concentrations fluorescence resonance energy transfer (FRET). atrophy, activation, upregulation SIRT1 FoxO1, along downregulation GPR39, confirmed T1D group. protected against inhibited (T1D + vs. T1D, all p < 0.0001), as evidenced increased grip strength (212.40 ± 11.08 163.90 10.95 gf), gastrocnemius index (10.67 0.44 8.80 0.72 mg/g), fibre cross-sectional area (978.20 144.00 580.20 103.30 μm2), serum (0.2335 0.0227 0.1561 0.0123 mg/L). down-regulated Atrogin-1 MuRF1, decreased formation autophagosomes (all 0.0001). RNA-seq indicated activation SIRT1/FoxO1 signalling pathway mice. LC3B, while upregulating P62 GPR39 0.05). down-regulation Both TC-G-1008 Atrogin-1, SIRT1, up-regulated inhibiting improving The beneficial anti-atrophic effects are diminished following treatment SRT1720 RAPA. Upon knockout, upregulated, downregulated. ZnSO₄-treated group remained unchanged (p > 0.05), indicating that supplementation did not affect ion entry acted through surface receptor GPR39. ZnSO4 inhibits excessive skeletal alleviates via GPR39-SIRT1/FoxO1 axis. These findings suggest may offer therapeutic strategy managing

Language: Английский

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Arsenic exposure provoked prostatic PANoptosis by inducing mitochondrial dysfunction in mice and WPMY-1 cells

Ecotoxicology and Environmental Safety, Journal Year: 2025, Volume and Issue: 295, P. 118139 - 118139

Published: April 1, 2025

Inorganic arsenic, a widespread environmental toxicant, significantly contributes to prostate injury. However, the exact cellular mechanisms remain unclear. This study explored involvement of pyroptosis, apoptosis, and necroptosis (PANoptosis), their interconnections in arsenic-induced Herein, by employing vitro (WPMY-1 cells exposed arsenic for 48 h with or without reactive oxygen species (ROS) mitochondrial ROS scavenger treatments) vivo (C57BL/6 mice were orally gavaged and/or N-acetylcysteine 90 consecutive days) models injury intervention, we demonstrated that sodium arsenite (NaAsO2) triggered damage-activated PANoptosis via Bax/Bcl-xL/caspase-3/Gasdermin E (GSDME) pathway Z-DNA binding protein 1/receptor-interacting kinases 1 (RIPK1)/RIPK3/mixed lineage kinase domain-like (MLKL) signaling pathway. Notably, treatment NaAsO2, GSDME, MLKL knockdown WPMY-1 increased phenotype PANoptosis. Mechanistically, GSDME-N, GSDMD-N, p-MLKL, cleaved caspase-3 levels (1.4-, 2.67-, 3.51-, 2.16-fold, respectively) NaAsO2-treated GSDME cells, whereas GSDME-N (1.30- 1.21-fold, cells. Our highlights crucial role dysfunction initiation during Furthermore, provide novel insights into connections between necroptosis, indicating proteins may act as regulators potential therapeutic targets

Language: Английский

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Cuproptosis and its potential role in musculoskeletal disease

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: April 11, 2025

Cuproptosis, a recently identified form of copper-dependent cell death, arises from intracellular copper dyshomeostasis. As an essential trace element, plays critical role in bioenergetic metabolism, redox regulation, and synaptic transmission. However, excessive exerts cytotoxic effects through multiple pathways, including increased reactive oxygen species (ROS) production, apoptotic cascade activation, necrotic membrane rupture, inflammatory responses, mitochondrial dysfunction. Distinct other death mechanisms, cuproptosis is characterized by ion binding to acetylated respiratory chain proteins, leading pathogenic protein aggregation, iron-sulfur cluster depletion, cellular collapse. Emerging evidence underscores aberrant accumulation resultant proteotoxic stress as pivotal contributors the pathogenesis musculoskeletal pathologies, osteoporosis, osteoarthritis, sarcopenia, osteosarcoma, intervertebral disc degeneration, spinal cord injury, biofilm-associated orthopedic infections. Understanding spatiotemporal regulation may provide novel opportunities for advancing diagnostic therapeutic approaches medicine. This review synthesizes current insights into molecular mechanisms cuproptosis, its diseases, potential biomarker-driven interventions.

Language: Английский

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How Cells Die in Psoriasis?

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3747 - 3747

Published: April 16, 2025

Psoriasis, a chronic immune-mediated inflammatory skin disorder characterized by keratinocyte hyperproliferation and cell infiltration, involves multiple distinct programmed death pathways in its pathogenesis. Following the Nomenclature Committee on Cell Death recommendations, we analyzed current literature examining diverse modes of cellular psoriatic lesions, with particular focus patterns their molecular signatures. Analysis revealed several mechanisms: autophagy dysfunction through IL-17A pathways, decreased apoptotic activity lesional skin, medication targeting anoikis psoriasis, upregulated necroptosis mediated RIPK1/MLKL signaling, gasdermin-mediated pyroptosis enhanced IL-1β secretion, coordinated PANoptotic activation specialized complexes, PARP1-mediated parthanatos promoting cutaneous inflammation, iron-dependent ferroptosis correlating Th22/Th17 responses, copper-dependent cuproptosis elevated MTF1/ATP7B/SLC31A1 expression, NETosis amplifying immune responses interaction Th17 axis. The intricate interplay between these mechanisms has led to development targeted therapeutic strategies, including mTOR inhibitors for modulation, RIPK1 necroptosis, various approaches NETosis, providing new directions more effective psoriasis treatments.

Language: Английский

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