Mitochondrial dysfunction is part of the mechanism of several human diseases. This negative circumstance may be induced by certain toxicants, as methylglyoxal (MG). MG is a reactive dicarbonyl presenting both endogenous and exogenous sources and is also able to induce protein cross-linking and glycation. Emodin (EM; 1,3,8-trihydroxy-6-methylanthracene-9,10-dione; C15H10O5) is a cytoprotective agent. Nonetheless, it was not previously demonstrated whether EM would be able to promote mitochondrial protection in cells challenged with MG. Therefore, we investigated here whether and how EM would prevent the MG-induced mitochondrial collapse in the human neuroblastoma SH-SY5Y cells. We found that a pretreatment (for 4 h) with EM at 40 μM prevented the MG-induced mitochondrial dysfunction (i.e., decreased activity of the complexes I and V, reduced adenosine triphosphate levels, and loss of mitochondrial membrane potential) in the SH-SY5Y cells. EM also prevented the redox impairment induced by MG in mitochondrial membranes. Inhibiting the adenosine monophosphate-activated protein kinase (AMPK) or silencing of the nuclear factor erythroid 2-related factor 2 (Nrf2), transcription factor abolished the EM-induced protection. Inhibition of heme oxygenase-1 (HO-1) also blocked the EM-induced mitochondrial protection. Therefore, EM protected the mitochondria by a mechanism dependent on the AMPK/Nrf2/HO-1 signaling pathway in MG-challenged SH-SY5Y cells.
Keywords: Antioxidant; Bioenergetics; Emodin; Methylglyoxal; Mitochondria; SH-SY5Y cells.