The effects of kahweol, a diterpene present in coffee, on the mitochondria of the human neuroblastoma SH-SY5Y cells exposed to hydrogen peroxide

Abstract

The oxidative phosphorylation (OXPHOS) system located in the mitochondria is the main source of adenosine triphosphate (ATP) in mammals. The mitochondria are also the main site of reactive oxygen species (ROS) production in those cells. Disruption of the mitochondrial redox biology has been seen in the onset and progression of neurodegenerative diseases. In this regard, we have tested here whether kahweol (KW; C₂₀H₂₆O₃), a diterpene present in coffee, would be able to promote mitochondrial protection in the human neuroblastoma SH-SY5Y cells exposed to hydrogen peroxide (H₂O₂). A pretreatment (for 12 h) with KW (at 10 μM) decreased the impact of H₂O₂ (at 300 μM) on the levels of oxidative stress markers in the mitochondrial membranes, as well as reduced the production of ROS by the organelles. KW pretreatment also suppressed the effects of H₂O₂ on the activity of components of the OXPHOS. The KW-induced mitochondria-related effects were blocked by inhibition of the phosphoinositide 3-kinase/Akt (PI3K/Akt) and p38 mitogen-activated protein kinase (MAPK) signaling pathways. Furthermore, silencing of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and inhibition of the heme oxygenase-1 (HO-1) enzyme abrogated the KW-induced protective effects on the mitochondria. Therefore, KW promoted mitochondrial protection by the PI3K/Akt and p38 MAPK/Nrf2/HO-1 axis in H₂O₂-challenged SH-SY5Y cells.

Keywords: Antioxidant; Kahweol; Mitochondria; Nrf2; Oxidative phosphorylation; Tricarboxylic acid cycle.