Aluminum-maltol induced oxidative stress and reduced AMPK activity via BCK-related energy supply failure in C6 cell

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.

Aluminum; Brain creatine kinase; Mitochondrial dysfunction; P-AMPK; Peroxide.