PMID:21787718

Citation	Lee, YJ, Lee, GJ, Baek, BJ, Heo, SH, Won, SY, Im, JH, Cho, MK, Nam, HS and Lee, SH (2011) Cadmium-induced up-regulation of aldo-keto reductase 1C3 expression in human nasal septum carcinoma RPMI-2650 cells: Involvement of reactive oxygen species and phosphatidylinositol 3-kinase/Akt. Environ. Toxicol. Pharmacol. 31:469-78
Abstract	Cadmium is a well-known toxic metal and occupational exposure to it is associated with lung cancer. In probing the possible non-genotoxic molecular targets of cadmium-induced nasal toxicity, we performed an mRNA differential display analysis for cadmium-treated human nasal septum carcinoma RPMI-2650 cells. Cadmium (≥ 0.5 μM) inhibited the cell proliferation. The intracellular ROS levels were induced by cadmium treatment. In addition, cadmium elicited the AKR1C3 expression. The cadmium-induced increase in AKR1C3 protein levels was suppressed by N-acetylcysteine (NAC) and, to a lesser extent, PI3K inhibitor (Ly294002). Cells pretreated with Ly294002 were more resistant to cadmium toxicity than control. The increase in AKR1C3 protein level was accompanied by an increase in the nuclear transcription factor Nrf2. Overall, our data suggest that cadmium-induced ROS cause up-regulation of AKR1C3 expression, at least partially via the activation of PI3K-related intracellular signaling pathways, and Nrf2 activation, thereby contributing to an adaptive intracellular response to cadmium toxicity.
Links	PubMed Online version:10.1016/j.etap.2011.03.006
Keywords	Acetylcysteine/pharmacology; Alcohol Oxidoreductases/biosynthesis; Antioxidants/pharmacology; Blotting, Western; Cadmium/toxicity; Cell Line, Tumor; Cell Survival/drug effects; Gene Expression Regulation, Enzymologic/drug effects; Humans; Indicators and Reagents; NF-E2-Related Factor 2/biosynthesis; NF-E2-Related Factor 2/genetics; Oncogene Protein v-akt/physiology; Phosphatidylinositol 3-Kinases/physiology; RNA, Messenger/biosynthesis; RNA, Messenger/genetics; Reactive Oxygen Species/metabolism; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction/drug effects; Up-Regulation/drug effects
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:AK1C3	involved_in	GO:0010942: positive regulation of cell death	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:AK1C3	involved_in	GO:0034614: cellular response to reactive oxygen species	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:AK1C3	involved_in	GO:0071276: cellular response to cadmium ion	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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