Identification of Genes Associated with Paraquat-Induced Toxicity in SH-SY5Y Cells by PCR Array Focused on Apoptotic Pathways

Abstract

Paraquat (PQ) (1,1-dimethyl-4,4′-bipyridinium dichloride), a widely used herbicide, has been suggested as a potential etiologic factor for the development of Parkinson's disease (PD). In this sense, understanding of the molecular mechanism underlying PQ-induced toxicity to neural cells is important for optimal use as well as for the development of new drugs. To gain insights into PQ-induced neurotoxicity, polymerase chain reaction (PCR) array analysis focused on a panel of apoptosis-related genes was performed using neuroblastoma SH-SY5Y cells. Up to 65 apoptosis-related genes were monitored. Our analysis of apoptotic process through microarray technology showed that in PQ-induced neuroblastoma SH-SY5Y cells, there is a different expression of BIK, CASP3, CASP7, CRADD, DAPK, FAS, and other related genes, in comparison to unstimulated cells. Evaluation of genes regulated differentially is essential for the development of therapeutic approaches in multifactorial diseases as PD. Our data provide a useful basis for screening candidate targets for early diagnosis and further intervention in PQ-mediated toxicity of neural cells.

The authors would like to thank to Maria Pura Delgado for helpful assistance in the laboratory work. Miguel Angel Ortiz Ortiz is a predoctoral recipient of a fellowship from Second Vice-presidency and Regional Ministry of Economy, Commerce and Innovation, from the Junta of Extremadura. Rosa Ana González Polo is currently recipient of a “Juan de la Cierva” grant from Spanish Ministry of Education and Science. This work was supported by grants PRI06B124 from Junta de Extremadura and PI040828 and PI070400 from FIS‐ISCIII, Spanish Ministry of Health and Consumer Affairs.