Free Radical Biology and Medicine, Год журнала: 2024, Номер unknown
Опубликована: Ноя. 1, 2024
Язык: Английский
Frontiers in Pharmacology, Год журнала: 2025, Номер 16
Опубликована: Янв. 29, 2025
Introduction Spinal cord injury (SCI) leads to severe inflammation and neuronal damage, resulting in permanent loss of motor sensory functions. Zinc ions have shown potential modulating cellular survival, making them a promising therapeutic approach for SCI. This study investigates the mechanisms zinc ion treatment SCI, focusing on its effects inflammation. Methods We used transcriptomic analysis identify key pathways genes involved inflammatory response mouse model In vitro studies assessed impact inflammation, cell polarization, apoptosis. IKBα expression was evaluated as target ions, both cultured cells vivo . Results Transcriptomic revealed that modulate through IKBα, which inhibits NF-κB activity. , upregulated expression, reducing These results were confirmed SCI model, where also reduced death. Discussion Our findings highlight novel mechanism by regulate upregulating inhibiting activation. suggests applications other conditions, warranting further investigation into their clinical benefits.
Язык: Английский
Процитировано
0
Ecotoxicology and Environmental Safety, Год журнала: 2025, Номер 295, С. 118139 - 118139
Опубликована: Апрель 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
Язык: Английский
Процитировано
0
Neurobiology of Disease, Год журнала: 2025, Номер unknown, С. 106907 - 106907
Опубликована: Апрель 1, 2025
PANoptosis represents a highly coordinated inflammatory programmed cell death governed by the assembly and activation of PANoptosome, which strategically integrate core molecular elements from pyroptosis, apoptosis, necroptosis. The triple-component pathways set themselves apart alternative regulated mechanisms through their unique capacity to concurrently process signals derived multiple death-signaling modalities, thereby coordinating multifaceted cellular defense system against diverse pathological insults. Pathogen-associated patterns synergistically interact with cytokine storms, oncogenic stress active PANoptosis, establishing this pathway as critical nexus in pathogenesis tumor immunomodulation. This crosstalk highlights promising therapeutic target for managing immune-related disorders malignant transformation. Emerging evidence links neuroinflammatory dysregulated between (apoptosis, necroptosis, pyroptosis) accidental necrosis, driving neuronal loss neural damage. Single-cell transcriptomics reveals spatially resolved signatures Alzheimer's hippocampal microenvironments sclerosis demyelinating plaques, distinct clusters correlating quantifiable metrics. PANoptosis-targeted therapies show preclinical promise alleviating neurovascular dysfunction while preserving physiological microglial surveillance functions. Accumulating linking (particularly PANoptosis) neurological underscores urgency deciphering its developing precision modulators next-generation therapies. review systematically deciphers PANoptosome associated cascades, evaluates roles multiscale regulatory networks, proposes frameworks advance neurology.
Язык: Английский
Процитировано
0
Advanced Science, Год журнала: 2024, Номер unknown
Опубликована: Сен. 18, 2024
Abstract Spinal cord injury (SCI) is a severe to the central nervous system, and its treatment always major medical challenge. Proinflammatory cell death considered an important factor affecting neuroinflammation prognosis after injury. PANoptosis, newly discovered type of proinflammatory death, regulates activation executioner molecules apoptosis, pyroptosis necroptosis through PANoptosome, providing new target for therapeutic intervention SCI. However, role regulatory mechanism in SCI are not yet elucidated. Here, based on proteomic data, YBX1 expression significantly increased neurons Guided by RIP‐seq, subsequent experiments reveal that promotes ZBP1 stabilizing Zbp1 mRNA, thereby aggravating ZBP1‐mediated PANoptosis. Furthermore, E3 ubiquitin ligase TRIM56 identified as endogenous inhibitor via molecular docking IP/MS analysis. Mechanistically, bound promoted ubiquitination, accelerating degradation. Taken together, these findings novel function regulating PANoptosis pathogenesis verified functions promote ubiquitin‐proteasomal degradation YBX1, insights into strategies.
Язык: Английский
Процитировано
3
Cellular Signalling, Год журнала: 2024, Номер 125, С. 111497 - 111497
Опубликована: Ноя. 1, 2024
Язык: Английский
Процитировано
1
Molecular Neurobiology, Год журнала: 2024, Номер unknown
Опубликована: Дек. 14, 2024
Язык: Английский
Процитировано
1
Free Radical Biology and Medicine, Год журнала: 2024, Номер unknown
Опубликована: Ноя. 1, 2024
Язык: Английский
Процитировано
0