Differences in ALDH2 activity in SH-SY5Y and HepG2 cell lines exposed to lead and ethanol

DEZA PONZIO, ROMINA; CEJAS, ROMINA B; ALBRECHT, PAULA A.; FERNANDEZ HUBEID, LUCIA; CANCELA, LILIANA M.; IRAZOQUI, FERNANDO J; VIRGOLINI MIRIAM B

Córdoba

Congreso; XXXIII Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias; 2018

Sociedad Argentina de Neurociencia

Several evidences demonstrate that the neurotoxicant lead (Pb) induces neurobehavioral alterations, including an altered response to drugs. We have previously reported that perinatally-Pb-exposed rats showed elevated ethanol (EtOH) intake. It is known that EtOH metabolism determines its motivational properties. In fact, centrally-formed acetaldehyde (ACD) promotes EtOH consumption, while peripheral ACD accumulation induces aversive effects. In both cases, aldehyde dehydrogenase (ALDH) is responsible for ACD oxidation to acetic acid. In the Pb-exposed rats, the elevated EtOH intake seems to be mediated by brain ACD accumulation, probably due to a reduced mitochondrial ALDH (ALDH2) activity and expression evidenced in these animals. In search of a mechanistic approach, in vitro experiments were performed in both SH-SY5Y and HepG2 cells, aimed to evaluate ALDH2 activity in a brain and liver like-environment. Both cell lines were exposed to Pb (5-200µM), EtOH (100-200 mM) or Pb + EtOH (10µM/200mM) for 24 h. The results resembled the in vivo data showing that Pb alone (5µM and 10µM) or in combination with EtOH inhibited ALDH2 activity only in the SH-SY5Y cells. On the contrast, no differences among groups emerged in the HepG2 cells, probably related to their low basal ALDH2 activity. Current studies are focalized in the assessment of ALDH2 expression and to explore the mechanisms that modulate ALDH2 function and ACD levels in each cell line in the presence of Pb and EtOH.