Modulation of ROS and interleukin-1beta production by arsenic trioxide and drugs that influence mitochondrial biogenesis and mitophagy in human keratinocytes

SALAVERRY LS; BESSONE M; PARRADO AC; MANGONE FM; SOTELO AD; LOMBARDO T; CANELLADA AM ; BLANCO G; SALAVERRY L.S.; PARRADO AC; MANGONE, F; RUGNA, A; GENTILE T; BLANCO, G; CANELLADA A; REY ESTELA

Mar del Plata

Congreso; Reunión Conjunta S A I C. S A F E. S A B. SAP 2 0 1 9; 2019

Chronic exposure to arsenicals is associated to a skin disease known a HACRE. Arsenic increases mitochondrial ROS (mtROS) and compromises mitochondrial function. Mitophagy (MF) and mitochondrial biogenesis (MB) are two critical processes in maintaining mitochondrial homeostasis. In addition, high levels of ROS may induce pro-inflammatory mediators like interleukin (IL)-1β. Here we explored the effect of drugs that modulate MB (valproic acid, VPA) and MF (vincristine, VCR) on mitochondrial mass (MM), superoxide anion production (O2-) and IL-1β levels, in HaCaT keratinocytes exposed to sublethal doses of arsenic trioxide (ATO). HaCaT cells were exposed to 1 µM ATO, 2 mM VPA and 0.75 µM VCR in 48h assays under several combinations, and stained with nonyl-acridine orange (NAO) and dihydroethidium (HE) to evaluate changes in MM and O2- respectively by flow cytometry. IL-1β levels were quantified by ELISA in cell culture supernatants. A p