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SAT1/ALOX15 Signaling Pathway Is Involved in Ferroptosis After Skeletal Muscle Contusion.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2024 Oct 21; Vol. 25 (20). Date of Electronic Publication: 2024 Oct 21. - Publication Year :
- 2024
-
Abstract
- Skeletal muscle contusion (SMC) is common in daily life and clinical practice, but the molecular mechanisms underlying SMC healing are unclear. Ferroptosis, a regulated cell death type, has gained attention recently. We observed iron overload in skeletal muscle following contusion through HE and Perls staining. Abnormal iron levels are highly likely to induce ferroptosis. Therefore, we aimed to explore whether iron overload after contusion leads to ferroptosis in skeletal muscle and the underlying mechanisms, which will help us understand the effects of iron abnormalities on skeletal muscle repair. Initially, we searched SMC gene expression profiles from the GEO database and used bioinformatics analysis to reveal ferroptosis occurrence. Then, we identified the gene sat1 plays an important role in this process. We further established a rat SMC model and treated rats with ferroptosis inhibitors (Ferrostatin-1, Deferoxamine). Our findings confirmed iron overload from SMC can lead to ferroptosis in rats. We also demonstrated that SAT1 can regulate ferroptosis by affecting ALOX15. Moreover, we constructed a ferroptosis L6 cell model and found that SAT1 knockdown significantly inhibited ALOX15 expression and reduced cellular lipid peroxidation. In conclusion, these results indicated ferroptosis can occur following SMC, and SAT1, as a key regulator, affects skeletal muscle injury healing by mediating high ALOX15 expression, which in turn regulates lipid peroxidation.
- Subjects :
- Animals
Rats
Male
Arachidonate 15-Lipoxygenase metabolism
Arachidonate 15-Lipoxygenase genetics
Iron Overload metabolism
Iron Overload pathology
Iron Overload genetics
Rats, Sprague-Dawley
Iron metabolism
Disease Models, Animal
Lipid Peroxidation
Cyclohexylamines pharmacology
Cell Line
Ferroptosis
Muscle, Skeletal metabolism
Muscle, Skeletal pathology
Muscle, Skeletal injuries
Signal Transduction
Contusions metabolism
Contusions pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 25
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 39457099
- Full Text :
- https://doi.org/10.3390/ijms252011317