Dexmedetomidine attenuates heat stress-induced oncosis in human skeletal muscle cells by activating the Nrf2/Ho-1 pathway.
10.12122/j.issn.1673-4254.2025.03.18
- Author:
Yang LIU
1
;
Yiqing JIA
2
;
Chengcheng LI
1
;
Handing MAO
2
;
Shuyuan LIU
2
;
Yi SHAN
1
Author Information
1. Department of Emergency Medicine, School of Medicine, South China University of Technology, Guangzhou 510006, China.
2. Department of Emergency Medicine, Sixth Medical Center of PLA General Hospital, Beijing 100048, China.
- Publication Type:Journal Article
- Keywords:
Nrf2/HO-1 pathway;
dexmedetomidine;
human skeletal muscle cells;
oncosis;
rhabdomyolysis
- MeSH:
Humans;
Dexmedetomidine/pharmacology*;
NF-E2-Related Factor 2/metabolism*;
Oxidative Stress/drug effects*;
Heat-Shock Response/drug effects*;
Signal Transduction/drug effects*;
Membrane Potential, Mitochondrial;
Muscle, Skeletal/cytology*;
Heme Oxygenase-1/metabolism*;
Apoptosis/drug effects*
- From:
Journal of Southern Medical University
2025;45(3):603-613
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To investigate the protective effects of dexmedetomidine (DEX) against heat stress (HS)-induced oncosis in human skeletal muscle cells (HSKMCs) and its underlying mechanisms.
METHODS:A HSKMC model of HS-induced oncosis were established by 43 ℃ water bath for 4 h, and the effects of treatments with 30 μmol/L DEX, ML385 (a Nrf2 inhibitor) +DEX, si-Nrf2+HS, and si-Nrf2+DEX prior to modeling on cell viability was assessed using CCK-8 assay. Oncosis characteristics were evaluated using transmission electron microscopy and Annexin V-FITC/PI flow cytometry. The oxidative stress markers (GSH, GSH-Px, MDA, SOD and ROS), mitochondrial membrane potential, energy metabolism, and inflammatory cytokines (TNF-α, IL-6 and IL-1β) in the cells were quantified using standard kits, and the expressions of porimin, caspase-3 and Nrf2 pathway proteins were analyzed using Western blotting and qRT-PCR.
RESULTS:HS induced typical oncotic features in HSKMCs including organelle swelling and cytoplasmic vacuolization. DEX pretreatment significantly attenuated these changes, reduced Annexin V+/PI+ cell ratio and cellular porimin expression, and lowered the levels of ROS and MDA while restoring GSH and SOD levels. DEX pretreatment also significantly increased the mitochondrial membrane potential and ATP level, upregulated the expressions of Nrf2, p-Nrf2, HO-1 and NQO1, and suppressed the expressions of TNF-α, IL-6 and IL-1β. The protective effects of DEX were obviously attenuated by interventions with ML385 or si-Nrf2.
CONCLUSIONS:DEX mitigates HS-induced HSKMC oncosis by activating the Nrf2/HO-1 pathway to relieve oxidative stress, mitochondrial dysfunction, and inflammatory responses.
