Impact of Cadmium on Intracellular Zinc Levels in HepG2 Cells: Quantitative Evaluations and Molecular Effects

BioMed Research International
Chiara UraniLaura Gribaldo

Abstract

Cadmium is classified as a human carcinogen, and its disturbance in zinc homeostasis has been well established. However, its extent as well as molecular mechanisms involved in cadmium carcinogenesis has yet to be fully clarified. To this end, we used the zinc specific probe Zinquin to visualize and to quantitatively evaluate changes in the concentration of labile zinc, in an in vitro model of human hepatic cells (HepG2) exposed to cadmium. A very large increase (+93%) of intracellular labile zinc, displaced by cadmium from the zinc proteome, was measured when HepG2 were exposed to 10 µM cadmium for 24 hrs. Microarray expression profiling showed that in cells, featuring an increase of labile zinc after cadmium exposure, one of the top regulated genes is Snail1 (+3.6), which is included in the adherens junction pathway and linked to cancer. In the same pathway MET, TGF-βR, and two members of the Rho-family GTPase, Rac, and cdc42 all implicated in the loss of adherence features and acquisition of migratory and cancer properties were regulated, as well. The microRNAs analysis showed a downregulation of miR-34a and miR-200a, both implicated in the epithelial-mesenchymal transition. These microRNAs results support the role played by ...Continue Reading

References

Jan 13, 2000·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·M S NasirT V O'Halloran
Sep 22, 2001·Toxicology in Vitro : an International Journal Published in Association with BIBRA·C UraniM Camatini
Feb 8, 2002·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·D Beyersmann, H Haase
May 8, 2002·Nature Reviews. Molecular Cell Biology·M Angela Nieto
Mar 5, 2003·BioTechniques·A I SaeedJ Quackenbush
Nov 6, 2003·Toxicology in Vitro : an International Journal Published in Association with BIBRA·C UraniM Camatini
Aug 6, 2005·Toxicology in Vitro : an International Journal Published in Association with BIBRA·C UraniG F Crosta
May 2, 2006·Statistical Applications in Genetics and Molecular Biology·Gordon K Smyth
May 6, 2006·Biochimica Et Biophysica Acta·David J Eide
Aug 23, 2006·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Artur Krezel, Wolfgang Maret
Oct 24, 2006·Toxicology in Vitro : an International Journal Published in Association with BIBRA·C UraniL Gribaldo
May 16, 2007·The Journal of Cell Biology·Satoru YamasakiToshio Hirano
Jul 30, 2008·Cell·Joan Massagué
Sep 1, 2009·Nature Methods·Jan L VinkenborgMaarten Merkx
Nov 3, 2009·Nucleic Acids Research·Minoru KanehisaMika Hirakawa
Nov 11, 2009·Toxicology in Vitro : an International Journal Published in Association with BIBRA·C UraniL Gribaldo
Mar 6, 2010·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Frank Thévenod
Nov 26, 2010·Nature Reviews. Molecular Cell Biology·Livio TrusolinoPaolo M Comoglio
Oct 26, 2011·The Journal of Cell Biology·Nam Hee KimJong In Yook
Mar 15, 2012·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Jie ZhengWei-Qun Ding
Jun 19, 2013·Journal of Internal Medicine·M HaneklausS L Masters
Nov 30, 2013·Metallomics : Integrated Biometal Science·Gaetano MalgieriCarla Isernia
Dec 21, 2013·Metallomics : Integrated Biometal Science·Julio A Landero FigueroaJoseph Caruso
Feb 18, 2014·Journal of Inorganic Biochemistry·Mohammad Ali NamdarghanbariDavid H Petering
Feb 18, 2014·Regulatory Toxicology and Pharmacology : RTP·Beatrice BoccaGiovanni Forte
Apr 12, 2014·Metallomics : Integrated Biometal Science·Sangyong Choi, Amanda J Bird
May 9, 2014·Metallomics : Integrated Biometal Science·Lu TangShizhong Wang
Jul 1, 2014·Small GTPases·Amine Sadok, Chris J Marshall
Aug 8, 2014·ISRN Toxicology·C UraniL Gribaldo
Aug 20, 2014·Current Biology : CB·Brian D AdamsFrank J Slack

❮ Previous
Next ❯

Citations

Jul 20, 2016·Toxicology in Vitro : an International Journal Published in Association with BIBRA·M ForcellaC Urani
Feb 14, 2017·Oxidative Medicine and Cellular Longevity·Raquel P SouzaMarcia E L Consolaro
Aug 20, 2019·Biological Trace Element Research·Shiyan GuZuoshun He
Jan 18, 2021·Biological Trace Element Research·Rasha S AlbeltagyOla H El-Habit
May 28, 2019·Journal of Agricultural and Food Chemistry·Yue WuShu-Ping Hui

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE3128

Methods Mentioned

BETA
fluorescence microscopy
PCR

Software Mentioned

Limma Bioconductor
TM4 system
Statgraphics Plus
Image Proplus
R

Related Concepts

Related Feeds

Adherens Junctions

An adherens junction is defined as a cell junction whose cytoplasmic face is linked to the actin cytoskeleton. They can appear as bands encircling the cell (zonula adherens) or as spots of attachment to the extracellular matrix (adhesion plaques). Adherens junctions uniquely disassemble in uterine epithelial cells to allow the blastocyst to penetrate between epithelial cells. Discover the latest research on adherens junctions here.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Cell Migration in Cancer and Metastasis

Migration of cancer cells into surrounding tissue and the vasculature is an initial step in tumor metastasis. Discover the latest research on cell migration in cancer and metastasis here.