RT Journal Article
T1 Oxidative stress and gene expression profiling of cell death pathways in alpha-cypermethrin-treated SH-SY5Y cells
A1 Romero Martínez, Manuel Alejandro
A1 Ramos Alonso, Eva
A1 Ares Lombán, Irma
A1 Castellano Santos, Víctor Jesús
A1 Martínez Caballero, Marta
A1 Martínez Larrañaga, María Rosa
A1 Anadón Navarro, Arturo Ramón
A1 Martínez Caballero, María Aranzazu
AB In this study, we investigated the induction of oxidative stress and apoptosis in human neuroblastoma cell line SH-SY5Y in response to alpha-cypermethrin (α-CYPER) exposure. MTT and LDH assays were carried out to assess the α-CYPER cytotoxicity. The IC50 value for α-CYPER was calculated to be 78.3 ± 2.98 µM for the MTT assay and 71.5 ± 3.94 µM for LDH assay. The pyrethroid α-CYPER (1-100 µM), in a dose-dependent manner, induced a significant increase in lipid peroxides measured as malondialdehyde (MDA) and in the levels of nitric oxide (NO). The neuroprotective role of three antioxidants, melatonin (MEL), Trolox and N-acetylcysteine (NAC) against α-CYPER-induced oxidative stress was examined. Compared to other antioxidants, MEL (1 µM) treatment showed the most effective protection against α-CYPER-induced lipid peroxidation and NO production. The effects of α-CYPER on gene expression profiling of cell death pathway in human neuroblastoma SH-SY5Y cells were also investigated. Of the 84 genes examined (P < 0.001; fold change >1.5), changes in mRNA levels were detected in 39 genes: 36 were up-regulated and 3 were down-regulated. A greater fold change reversion than 3.5-fold was observed on the up-regulated ATP6V1G2, BCL2, CASP9, FAS, GADD45A, SPATA2, SYCP2, ATG7, NFKB1, SNCA, ULK1 and JPH3 genes. The results demonstrated that α-CYPER alters the expression of apoptosis-, autophagy- and necrosis genes as well as induces oxidative stress which may lead to DNA damage. The detailed knowledge of the changes in gene expression obtained will provide a basis for further elucidating the molecular mechanisms of the α-CYPER-induced toxicity.
PB Springer
SN 0340-5761
YR 2017
FD 2017
LK https://hdl.handle.net/20.500.14352/97730
UL https://hdl.handle.net/20.500.14352/97730
LA eng
NO Romero A, Ramos E, Ares I, Castellano V, Martínez M, Martínez-Larrañaga MR, Anadón A, Martínez MA. Oxidative stress and gene expression profiling of cell death pathways in alpha-cypermethrin-treated SH-SY5Y cells. Arch Toxicol. 2017 May;91(5):2151-2164. doi: 10.1007/s00204-016-1864-y. Epub 2016 Oct 4. PMID: 27704156.
NO Comunidad de Madrid
DS Docta Complutense
RD 6 abr 2025