Apolipoprotein A-I induce (p62) expression via Nrf2 dependent

DIAZ LUDOVICO I; TREJO SA; BECERRA R.; GONZALEZ M

Mendoza

Congreso; LVIII Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology Research; 2022

SAIB

APOLIPOPROTEIN-AI INDUCE p62 EXPRESSION VIA Nrf2-DEPENDENT1 Díaz Ludovico Ivo; 2 Trejo Sebastián; 1 Becerra Romina; 1 Gonzalez Marina Cecilia.1 INIBIOLP (Institute of Biochemical Research of La Plata), Medicine School of theNational University of La Plata. La Plata. Buenos Aires, Argentina.2 YPF Tecnología (Y-TEC). Berisso, Buenos Aires, Argentina.Apolipoprotein A-I (apoA-I) is the major protein component of high-densitylipoproteins (HDLs). The apoA-I interaction with cells produces a complex intracellularsignal transduction system activation that leads cholesterol endogenous poolsmovilization and anti-inflammatory respons. We have performed a proteomic profile inTHP-1 cells treated with apoA-I in order to study differences in the level of total proteinexpression compared to controls without protein treatment. The total protein extract wasanalyzed in an orbitrap/quadrupole and processed by two different software to obtainrobust data. Several proteins with a significant level of expression (p≤0.05) in cellstreated with apoA-I were identified, such as the protein Sequestosome-1 (P62). P62 is amultifunctional chaperone that transports non-functional macromolecules toautophagosomes for degradation and could be regulated by the nuclear factor-erythroid2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/keap1) antioxidantresponse system. Also, we have observed a significant increase in the heme oxygenase1(HO1) expression levels, a key enzyme transcribed by Nrf2. When Nrf2 was inhibitedby retinoic acid (ATRA), P62 expression levels decreased by 40-50% in treated cells(ATRA+ ApoA-I). We conclude that the P62 expression increase in apoA-I cellstreatment would be related to the activation of the Nrf2/keap1 antioxidant system.