Artículo
ALDH2 inhibition by lead and ethanol elicits redox imbalance and mitochondrial dysfunction in SH-SY5Y human neuroblastoma cell line: Reversion by Alda-1
Deza Ponzio, Romina
; Albrecht, Paula Alejandra
; Fernandez Hubeid, Lucia Eugenia
; Eichwald, Tuany; Cejas, Romina Beatríz
; Garay, Yohana Camila
; Rivera Meza, Mario Francis; Latini, Alexandra; Irazoqui, Fernando Jose
; Virgolini, Miriam Beatriz
Fecha de publicación:
07/2023
Editorial:
Elsevier Science
Revista:
Neurotoxicology
ISSN:
0161-813X
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Lead (Pb), a common environmental contaminant, and ethanol (EtOH), a widely available drug of abuse, are well-known neurotoxicants. In vivo, experimental evidence indicates that Pb exposure affects oxidative EtOH metabolism with a high impact on living organisms. On these bases, we evaluated the consequences of combined Pb and EtOH exposure on aldehyde dehydrogenase 2 (ALDH2) functionality. In vitro exposure to 10 µM Pb, 200 mM EtOH, or their combination for 24 h reduced ALDH2 activity and content in SH-SY5Y human neuroblastoma cells. In this scenario, we observed mitochondrial dysfunction characterized by reduced mass and membrane potential, decreased maximal respiration, and spare capacity. We also evaluated the oxidative balance in these cells finding a significant increase in reactive oxygen species (ROS) production and lipid peroxidation products under all treatments accompanied by an increase in catalase (CAT) activity and content. These data suggest that ALDH2 inhibition induces the activation of converging cytotoxic mechanisms resulting in an interplay between mitochondrial dysfunction and oxidative stress. Notably, NAD+ (1 mM for 24 h) restored ALDH2 activity in all groups, while an ALDH2 enhancer (Alda-1, 20 µM for 24 h) also reversed some of the deleterious effects resulting from impaired ALDH2 function. Overall, these results reveal the crucial role of this enzyme on the Pb and EtOH interaction and the potential of activators such as Alda-1 as therapeutic approaches against several conditions involving aldehydes accumulation.
Palabras clave:
ALDA-1
,
ALDEHYDE DEHYDROGENASE 2 (ALDH2)
,
ETHANOL
,
LEAD
,
MITOCHONDRIA
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Articulos(CIQUIBIC)
Articulos de CENTRO DE INVEST.EN QCA.BIOL.DE CORDOBA (P)
Articulos de CENTRO DE INVEST.EN QCA.BIOL.DE CORDOBA (P)
Articulos(IFEC)
Articulos de INST. DE FARMACOLOGIA EXPERIMENTAL DE CORDOBA
Articulos de INST. DE FARMACOLOGIA EXPERIMENTAL DE CORDOBA
Citación
Deza Ponzio, Romina; Albrecht, Paula Alejandra; Fernandez Hubeid, Lucia Eugenia; Eichwald, Tuany; Cejas, Romina Beatríz; et al.; ALDH2 inhibition by lead and ethanol elicits redox imbalance and mitochondrial dysfunction in SH-SY5Y human neuroblastoma cell line: Reversion by Alda-1; Elsevier Science; Neurotoxicology; 97; 7-2023; 12-24
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