Proteomics as a tool for examining the toxicity of heavy metals

Examining the toxic effects of heavy metals on protein expression can be useful for gaining insight into the biomolecular mechanisms of toxicity and for identifying potential candidate metal-specific protein markers of exposure and response. In this article, we present the state of the art of proteomics in metal-toxicity-related studies. We consider different methods used for sample preparation that depend on the nature of the sample (plants, microorganisms and animals). We also describe different proteomic strategies, both gel-based and gel-free technologies, including two-dimensional gel electrophoresis (2-DE) and multi-dimensional protein-identification technology (MudPIT). We critically review the advantages and the disadvantages of such techniques and discuss the main studies carried out so far. We also comment on future applications and potential research interests within this field.

[1]  L. Hoffmann,et al.  Combining proteomics and metabolite analyses to unravel cadmium stress-response in poplar leaves. , 2009, Journal of proteome research.

[2]  C. Vannini,et al.  Proteomic analysis of chromate-induced modifications in Pseudokirchneriella subcapitata. , 2009, Chemosphere.

[3]  M. Hajduch,et al.  Proteomic analysis of mature soybean seeds from the Chernobyl area suggests plant adaptation to the contaminated environment. , 2009, Journal of proteome research.

[4]  Gang Wu,et al.  A critical review on the bio-removal of hazardous heavy metals from contaminated soils: issues, progress, eco-environmental concerns and opportunities. , 2010, Journal of hazardous materials.

[5]  S. Kennedy The role of proteomics in toxicology: identification of biomarkers of toxicity by protein expression analysis , 2002, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[6]  H. Hartikainen,et al.  Protective effect of selenium in Broccoli (Brassica oleracea) plants subjected to cadmium exposure. , 2008, Journal of agricultural and food chemistry.

[7]  C. Baker-Austin,et al.  Molecular insight into extreme copper resistance in the extremophilic archaeon 'Ferroplasma acidarmanus' Fer1. , 2005, Microbiology.

[8]  He-qing Huang,et al.  Proteomic changes in response to acute cadmium toxicity in gill tissue of Paralichthys olivaceus. , 2009, Environmental toxicology and pharmacology.

[9]  M. Palacios,et al.  Novel insights into the bottom-up mass spectrometry proteomics approach for the characterization of Pt-binding proteins: The insulin-cisplatin case study. , 2010, The Analyst.

[10]  K. Stühler,et al.  Difference gel electrophoresis , 2009, Electrophoresis.

[11]  Determination and removal of impurities in 2-D LC-MS of peptides. , 2006, Journal of separation science.

[12]  Sang Yeol Lee,et al.  Comparative proteomic analysis of the short-term responses of rice roots and leaves to cadmium. , 2010, Journal of plant physiology.

[13]  C. Vannini,et al.  Thiol-peptide level and proteomic changes in response to cadmium toxicity in Oryza sativa L. roots , 2007 .

[14]  Wei Wang,et al.  Protein extraction for two‐dimensional electrophoresis from olive leaf, a plant tissue containing high levels of interfering compounds , 2003, Electrophoresis.

[15]  Dacheng Tian,et al.  Comparative proteome analysis of differentially expressed proteins induced by Al toxicity in soybean. , 2007, Physiologia plantarum.

[16]  S. Tommasi,et al.  SELDI-TOF serum proteomics and breast cancer: which perspective? , 2008, Expert review of proteomics.

[17]  W. Hurkman,et al.  Solubilization of plant membrane proteins for analysis by two-dimensional gel electrophoresis. , 1986, Plant physiology.

[18]  Olivier Barré,et al.  Copper Induction of Lactate Oxidase of Lactococcus lactis: a Novel Metal Stress Response , 2007, Journal of bacteriology.

[19]  J. Gaillard,et al.  Urine proteomic profiling of uranium nephrotoxicity. , 2009, Biochimica et biophysica acta.

[20]  Lei Zhang,et al.  Heavy metals chromium and neodymium reduced phosphorylation level of heat shock protein 27 in human keratinocytes. , 2010, Toxicology in vitro : an international journal published in association with BIBRA.

[21]  A. Sanz-Medel,et al.  Absolute and site-specific quantification of protein phosphorylation using integrated elemental and molecular mass spectrometry: its potential to assess phosphopeptide enrichment procedures. , 2008, Analytical chemistry.

[22]  M. Kulkarni,et al.  Characterization of the proteins of bacterial strain isolated from contaminated site involved in heavy metal resistance--a proteomic approach. , 2007, Journal of biotechnology.

[23]  Thomas A Neubert,et al.  Sample preparation for serum/plasma profiling and biomarker identification by mass spectrometry , 2006, Journal of Chromatography A.

[24]  Jirun Peng,et al.  SELDI protein chip technology for the detection of serum biomarkers for liver disease. , 2009, Protein and peptide letters.

[25]  M. Stockler,et al.  Identification of candidate biomarkers of therapeutic response to docetaxel by proteomic profiling. , 2009, Cancer research.

[26]  S. Campuzano,et al.  Molecular mechanisms of methylmercury-induced cell death in human HepG2 cells. , 2010, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[27]  C. Cámara,et al.  The effect of the presence of volatile organoselenium compounds on the determination of inorganic selenium by hydride generation , 2003, Analytical and bioanalytical chemistry.

[28]  M. Molloy,et al.  Membrane proteins and proteomics: Un amour impossible? , 2000, Electrophoresis.

[29]  J. A. Smith,et al.  Responses to Nickel in the Proteome of the Hyperaccumulator Plant Alyssum lesbiacum , 2005, Biometals.

[30]  Jeung Joo Lee,et al.  Comparative proteomic study of arsenic‐induced differentially expressed proteins in rice roots reveals glutathione plays a central role during As stress , 2008, Proteomics.

[31]  J. Bandow Comparison of protein enrichment strategies for proteome analysis of plasma , 2010, Proteomics.

[32]  N. Ahsan,et al.  Analysis of arsenic stress-induced differentially expressed proteins in rice leaves by two-dimensional gel electrophoresis coupled with mass spectrometry. , 2010, Chemosphere.

[33]  L. Zieske A perspective on the use of iTRAQ reagent technology for protein complex and profiling studies. , 2006, Journal of experimental botany.

[34]  P. Kakkar,et al.  Biological markers for metal toxicity. , 2005, Environmental toxicology and pharmacology.

[35]  Steve Goodison,et al.  A comparative phosphoproteomic analysis of a human tumor metastasis model using a label‐free quantitative approach , 2010, Electrophoresis.

[36]  J. Casal,et al.  Differential protein expression on the cell surface of colorectal cancer cells associated to tumor metastasis , 2010, Proteomics.

[37]  Kristina L. Ford,et al.  Increased Abundance of Proteins Involved in Phytosiderophore Production in Boron-Tolerant Barley1[C][W] , 2007, Plant Physiology.

[38]  B. Marrone,et al.  Proteomic analysis of beryllium‐induced genotoxicity in an Escherichia coli mutant model system , 2006, Proteomics.

[39]  B. Trathnigg,et al.  Characterization of poly(ethylene glycol)-b-poly(epsilon-caprolactone) by two-dimensional liquid chromatography. , 2009, Journal of separation science.

[40]  J. Giovannoni,et al.  Tackling the plant proteome: practical approaches, hurdles and experimental tools. , 2004, The Plant journal : for cell and molecular biology.

[41]  F. Silvestre,et al.  Differential protein expression profiles in anterior gills of Eriocheir sinensis during acclimation to cadmium. , 2006, Aquatic toxicology.

[42]  M. Osaki,et al.  Metabolic alterations proposed by proteome in rice roots grown under low P and high Al concentration under low pH , 2007 .

[43]  Sarka Beranova-Giorgianni,et al.  Proteome analysis by two-dimensional gel electrophoresis and mass spectrometry: strengths and limitations , 2003 .

[44]  L. Zolla,et al.  Proteomic analysis of multiprotein complexes in the thylakoid membrane upon cadmium treatment. , 2009, Journal of proteome research.

[45]  Xin Lu,et al.  Proteomic Profiling in the Sera of Workers Occupationally Exposed to Arsenic and Lead: Identification of Potential Biomarkers , 2005, Biometals.

[46]  C. Lian,et al.  Proteomic identification of small, copper-responsive proteins in germinating embryos of Oryza sativa. , 2009, Annals of botany.

[47]  Gérard Steinmetz,et al.  Transcriptomic and proteomic responses of human renal HEK293 cells to uranium toxicity , 2005, Proteomics.

[48]  K. Chan,et al.  Changes in the protein expression profiles of the Hepa-T1 cell line when exposed to Cu2+. , 2009, Aquatic toxicology.

[49]  Xinxiang Peng,et al.  Identification of aluminum‐responsive proteins in rice roots by a proteomic approach: Cysteine synthase as a key player in Al response , 2007, Proteomics.

[50]  K. Fytianos Speciation analysis of heavy metals in natural waters: a review. , 2001, Journal of AOAC International.

[51]  N. Ahsan,et al.  Physiological and protein profiles alternation of germinating rice seedlings exposed to acute cadmium toxicity. , 2007, Comptes rendus biologies.

[52]  Ronald J. Moore,et al.  Toward a Human Blood Serum Proteome , 2002, Molecular & Cellular Proteomics.

[53]  R. Wait,et al.  Growth and protein profile changes in Lepidium sativum L. plantlets exposed to cadmium , 2007 .

[54]  C. Junot,et al.  The early responses of Arabidopsis thaliana cells to cadmium exposure explored by protein and metabolite profiling analyses , 2006, Proteomics.

[55]  D. Otzen,et al.  Proteomic changes in response to chromium(VI) toxicity in Pseudomonas aeruginosa. , 2010, Bioresource technology.

[56]  M. Toledano,et al.  A Proteome Analysis of the Cadmium Response in Saccharomyces cerevisiae * , 2001, The Journal of Biological Chemistry.

[57]  M. Gómez-Gómez,et al.  Top-down mass spectrometric approach for the full characterization of insulin-cisplatin adducts. , 2009, Analytical chemistry.

[58]  Daniel López-Ferrer,et al.  Improved Method for Differential Expression Proteomics Using Trypsin-catalyzed 18O Labeling with a Correction for Labeling Efficiency *S , 2007, Molecular & Cellular Proteomics.

[59]  Qing-Yu He,et al.  Proteomic and functional analyses reveal a dual molecular mechanism underlying arsenic-induced apoptosis in human multiple myeloma cells. , 2009, Journal of proteome research.

[60]  M. Huertas,et al.  Cyanide metabolism of Pseudomonas pseudoalcaligenes CECT5344: role of siderophores. , 2006, Biochemical Society transactions.

[61]  Sung-Eun Lee,et al.  Proteomic evaluation of cadmium toxicity on the midge Chironomus riparius Meigen larvae , 2006, Proteomics.

[62]  M. Usami,et al.  Proteomic analysis of indium embryotoxicity in cultured postimplantation rat embryos. , 2009, Reproductive toxicology.

[63]  A. van Dorsselaer,et al.  Early manganese‐toxicity response in Vigna unguiculata L. – a proteomic and transcriptomic study , 2008, Proteomics.

[64]  M. Usami,et al.  Two-dimensional electrophoresis of protein from cultured postimplantation rat embryos for developmental toxicity studies. , 2007, Toxicology in vitro : an international journal published in association with BIBRA.

[65]  M. Costa,et al.  Alterations to proteome and tissue recovery responses in fish liver caused by a short-term combination treatment with cadmium and benzo[a]pyrene. , 2010, Environmental pollution.

[66]  E. Petricoin,et al.  Use of proteomic patterns in serum to identify ovarian cancer , 2002, The Lancet.

[67]  F. Mahboudi,et al.  Proteome modifications of juvenile beluga (Huso huso) brain as an effect of dietary methylmercury. , 2009, Comparative biochemistry and physiology. Part D, Genomics & proteomics.

[68]  G. Nordberg,et al.  Biomarkers of cadmium and arsenic interactions. , 2005, Toxicology and applied pharmacology.

[69]  M. Bebianno,et al.  Effect of cadmium in the clam Ruditapes decussatus assessed by proteomic analysis. , 2009, Aquatic toxicology.

[70]  M. Tena,et al.  Maize response to acute arsenic toxicity as revealed by proteome analysis of plant shoots , 2006, Proteomics.

[71]  F. Grassi,et al.  Zea mays L. protein changes in response to potassium dichromate treatments. , 2006, Chemosphere.

[72]  S. Ahamed,et al.  Arsenic speciation in rice, straw, soil, hair and nails samples from the arsenic-affected areas of Middle and Lower Ganga plain , 2007, Journal of environmental science and health. Part A, Toxic/hazardous substances & environmental engineering.

[73]  H. Braun,et al.  Effect of Manganese Toxicity on the Proteome of the Leaf Apoplast in Cowpea1 , 2003, Plant Physiology.

[74]  J. Rose,et al.  A critical evaluation of sample extraction techniques for enhanced proteomic analysis of recalcitrant plant tissues , 2004, Proteomics.

[75]  S. Clemens,et al.  Proteome changes in Arabidopsis thaliana roots upon exposure to Cd2+. , 2006, Journal of experimental botany.

[76]  Qing-Yu He,et al.  Proteomic analyses of arsenic‐induced cell transformation with SELDI‐TOF ProteinChip® technology , 2003, Journal of cellular biochemistry.

[77]  S. Komatsu,et al.  Recent developments in the application of proteomics to the analysis of plant responses to heavy metals , 2009, Proteomics.

[78]  He-qing Huang,et al.  Selection and Identification of Differential Proteins of Liver Revealed with Proteomics in Achatina Fulica Under Induction of Cadmium , 2009 .

[79]  G. Berta,et al.  Proteomic characterization of copper stress response in Cannabis sativa roots , 2007, Proteomics.

[80]  J. Kellermann ICPL--isotope-coded protein label. , 2008, Methods in molecular biology.

[81]  P. Puntervoll,et al.  Responses in the brain proteome of Atlantic cod (Gadus morhua) exposed to methylmercury. , 2010, Aquatic toxicology.

[82]  H. Yoon,et al.  Excess copper induced physiological and proteomic changes in germinating rice seeds. , 2007, Chemosphere.

[83]  M. Tena,et al.  Proteome analysis of maize roots reveals that oxidative stress is a main contributing factor to plant arsenic toxicity. , 2005, Phytochemistry.

[84]  L. Hoffmann,et al.  Quantitative changes in protein expression of cadmium‐exposed poplar plants , 2008, Proteomics.

[85]  J. Rose,et al.  Sample extraction techniques for enhanced proteomic analysis of plant tissues , 2006, Nature Protocols.

[86]  M. Hajduch,et al.  A Systematic Proteomic Study of Seed Filling in Soybean. Establishment of High-Resolution Two-Dimensional Reference Maps, Expression Profiles, and an Interactive Proteome Database1[w] , 2005, Plant Physiology.

[87]  K. Kang,et al.  Two‐dimensional electrophoretic analysis of rice proteins by polyethylene glycol fractionation for protein arrays , 2001, Electrophoresis.

[88]  G. Visioli,et al.  A 2-D liquid-phase chromatography for proteomic analysis in plant tissues. , 2006, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[89]  Dirk Wolters,et al.  Proteomic survey of metabolic pathways in rice , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[90]  J. Garin,et al.  Metabolomic, proteomic and biophysical analyses of Arabidopsis thaliana cells exposed to a caesium stress. Influence of potassium supply. , 2006, Biochimie.

[91]  Shanyu Li,et al.  Polyethylene glycol fractionation improved detection of low-abundant proteins by two-dimensional electrophoresis analysis of plant proteome. , 2006, Phytochemistry.

[92]  Surong Zhang,et al.  Changes in the brain mitochondrial proteome of male Sprague-Dawley rats treated with manganese chloride. , 2005, Toxicology and applied pharmacology.

[93]  P. Kestemont,et al.  Proteomic response to sublethal cadmium exposure in a sentinel fish species, Cottus gobio. , 2011, Journal of proteome research.

[94]  Yan Ding,et al.  Responses of wheat seedlings to cadmium, mercury and trichlorobenzene stresses. , 2009, Journal of environmental sciences.

[95]  T. K. Hayes,et al.  Rarity gives a charm: evaluation of trace proteins in plasma and serum , 2005, Expert review of proteomics.

[96]  Qing-Yu He,et al.  Proteomic analysis of chromium cytotoxicity in cultured rat lung epithelial cells , 2008, Proteomics.

[97]  James A Wells,et al.  Sampling the N-terminal proteome of human blood , 2010, Proceedings of the National Academy of Sciences.

[98]  Angelika Görg,et al.  A proteome analysis of the cadmium and mercury response in Corynebacterium glutamicum , 2008, Proteomics.