Alterations in metabolism-related genes induced in SHSY5Y cells by okadaic acid exposure

J Toxicol Environ Health A. 2012;75(13-15):844-56. doi: 10.1080/15287394.2012.690703.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine Nucleotide Translocator 1 / genetics
  • Adenine Nucleotide Translocator 1 / metabolism
  • Amino Acyl-tRNA Synthetases / genetics
  • Amino Acyl-tRNA Synthetases / metabolism
  • Cell Line, Tumor
  • Electron Transport Complex IV / genetics
  • Electron Transport Complex IV / metabolism
  • Enzyme Inhibitors / toxicity
  • Gene Expression Regulation / drug effects*
  • Glyceraldehyde-3-Phosphate Dehydrogenases / genetics
  • Glyceraldehyde-3-Phosphate Dehydrogenases / metabolism
  • Humans
  • Marine Toxins / toxicity*
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / drug effects*
  • Neurons / enzymology
  • Neurons / metabolism
  • Okadaic Acid / toxicity*
  • Protein Phosphatase 1 / antagonists & inhibitors
  • Protein Phosphatase 2 / antagonists & inhibitors
  • RGS Proteins / genetics
  • RGS Proteins / metabolism
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Shellfish Poisoning / enzymology
  • Shellfish Poisoning / metabolism
  • Time Factors

Substances

  • Adenine Nucleotide Translocator 1
  • Enzyme Inhibitors
  • Marine Toxins
  • Membrane Transport Proteins
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Mitochondrial Proteins
  • Nerve Tissue Proteins
  • RGS Proteins
  • RGS5 protein, human
  • RNA, Messenger
  • TOMM5 protein, human
  • Okadaic Acid
  • Glyceraldehyde-3-Phosphate Dehydrogenases
  • cytochrome C oxidase subunit II
  • Electron Transport Complex IV
  • Protein Phosphatase 1
  • Protein Phosphatase 2
  • Amino Acyl-tRNA Synthetases
  • glutaminyl-tRNA synthetase