BENZOPHENONES 2 (BP2) AND 3 (BP3) AFFECT CELLULAR ADAPTIVE RESPONSES IN THE PANCREATIC BETA CELL LINE MIN6B1 IN THE PRESENCE OF THE AUTOPHAGY INHIBITOR CHLOROQUINE

MARINA OLGA FERNANDEZ; DAMASIA BECU DE VILLALOBOS; FLORENCIA SZULAK; ELEONORA M. SORIANELLO

Mar del Plata

Congreso; REUNIÓN ANUAL DE SOCIEDADES DE BIOCIENCIA 2019; 2019

Benzophenones used as ultraviolet light blockers in plastic packaging of food and in sunscreens, are considered endocrine disruptors. In addition, autophagy is a mechanism of degradation and recycling of cellular components essential for cell homeostasis. In pancreatic beta cells autophagy has a fundamental role in relieving endoplasmic reticulum (ER) stress caused by misfolded proteins, including insulin. Our research focused on studying the effect of BP2 and BP3 on mouse pancreatic beta cell line MIN6B1 function in the presence of the autophagy inhibitor Chloroquine (CQ). The results showed that basal insulin secretion was inhibited by the lysosomotropic compound CQ (10 μM), and also by BP3 (10-5 M) both when incubated alone and in the presence of CQ. In addition, CQ triggered an adaptive response involving induction of genes related to lysosomal biogenesis, Lamp2, or autophagy, Sqstm1/p62. Interestingly, BP3 significantly reverted the induction of Lamp2 and showed a strong tendency to counteract the induction of Sqstm1/p62 by CQ, in addition to decreasing the mRNA levels of the autophagy marker Ulk1 both basally and in the presence of CQ. BP2 (10-5 M) only reverted the induction of Lamp2. Interestingly, these effects failed to alter the protein levels of LC3II or SQSTM1/p62, or the autophagic flux itself. Regarding ER stress markers, BP3 decreased the transcription of Xbp1 and its spliced form, and counteracted the induction of Chop and Grp78/Bip triggered by CQ. Likewise, BP2 partially reverted the induction of Grp78/BiP mRNA by CQ. We conclude that benzophenones, mainly BP3, and to a lesser extent BP2, counteract adaptive responses related to autophagy, lysosomal biogenesis and reticulum stress, in a condition of lysosomal stress and autophagy block caused by CQ. Since BP3 also inhibited basal insulin secretion, we suggest that both BP2 and BP3 alter the function of the pancreatic beta cell.Supported by CONICET, ANPCyT, Fund. Rene Baron and Fund. Williams grants.