Alterations in Metabolism-Related Genes Induced in SHSY5Y Cells by Okadaic Acid Exposure

Abstract

Okadaic acid (OA) is a widely distributed marine toxin produced by several phytoplanktonic species and responsible for diarrheic shellfish poisoning in humans. At the molecular level OA is a specific inhibitor of several types of serine/threonine protein phosphatases. Due to this enzymic inhibition, OA was reported to induce numerous alterations in relevant cellular physiological processes, including several metabolic pathways such as glucose uptake, lipolysis and glycolysis, heme metabolism, and glycogen and protein synthesis. In order to further understand the underlying mechanisms involved in OA-induced effects on cellular metabolism, the expression levels of six genes related to different catabolic and anabolic metabolism-related processes were analyzed by real-time polymerase chain reaction. Specifically, the expression patterns of GAPDH, TOMM5, SLC25A4, COII, QARS, and RGS5 genes were determined in SHSY5Y human neuroblastoma cells exposed to OA for 3, 24, or 48 h. All these genes showed alterations in their expression levels after at least one of the OA treatments tested. These alterations provide a basis to understand the mechanisms underlying the previously described OA-induced effects on different metabolic processes, mainly regarding glucose and mitochondrial metabolism. However, other OA-induced affected genes can not be ruled out, and further studies are required to more comprehensively characterize in the mechanisms of OA-induced interaction on cell metabolism.

Acknowledgments

This work was funded by a grant from the Spanish Ministry of Science and Innovation (PSI2010-15115). V. Valdiglesias was supported by a fellowship from the University of A Coruña. The authors thank the Genomics Service from INIBIC (Complejo Hospitalario Universitario A Coruña) for providing their facilities. Funding from the New INDIGO program (NanoLINEN – 045-036-073 project, PIM2010ENI-00632) is gratefully acknowledged.