Aluminum-maltol induced oxidative stress and reduced AMPK activity via BCK-related energy supply failure in C6 cell.
Ecotoxicol Environ Saf
; 270: 115831, 2024 Jan 15.
Article
en En
| MEDLINE
| ID: mdl-38101974
ABSTRACT
Aluminum (Al) exposure significantly interferes with the energy supply in astrocytes, which may be a potential mechanism of Al-induced neurotoxicity. This study was designed to explore the mechanisms of Al-induced energy supply impairment in rat C6 astroglioma cell line. Aluminum-maltolate (Al(mal)3) (0.1 mM, 24 h) exposure significantly decreased brain-type creatine kinase (BCK) co-localization with the endoplasmic reticulum (ER) and resulted in mitochondrial dysfunctions, accompanied by a decrease in AMPK phosphorylation. The results of molecular docking showed that Al(mal)3 increased BCK's hydrophobicity and hindered the localization movement of BCK between subcells·H2O2 co-administration was found to exacerbate mitochondrial dysfunction, Ca2+ dyshomeostasis, and apoptosis. After treated with Al(mal)3, additional oxidative stress contributed to BCK activity inhibition but did not promote a further decrease in AMPK phosphorylation. The activation of p-AMPK by its agonist can partially restore mitochondrial function, BCK activity, and ER-localized-BCK levels in Al(mal)3-treated astrocytes. In summary, Al exposure resulted in a sustained depletion of the mitochondrial and antioxidant systems, which was associated with reduced p-AMPK activity and decreased ER-localized-BCK levels in astrocytes. This study provides a theoretical basis for exploring the mechanisms of neurotoxicity induced by Al exposure.
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Bases de datos:
MEDLINE
Asunto principal:
Compuestos Organometálicos
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Pironas
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Proteínas Quinasas Activadas por AMP
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Aluminio
Límite:
Animals
Idioma:
En
Revista:
Ecotoxicol Environ Saf
Año:
2024
Tipo del documento:
Article
País de afiliación:
China