Metallomics: the concept and methodology

Mounicou, Sandra; Szpunar, Joanna; Łobiński, Ryszard

doi:10.1039/b713633c

Cited by 309 publications

(261 citation statements)

References 115 publications

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“…Thus, it is important to apply agnostic approaches to detect a larger cross-section of toxic chemicals arising from all sources (Rappaport and Smith, 2010). Fortunately, some ''omics'' methods offer unbiased means for characterizing exposures to several important classes of toxicants, namely, metals (metallomics) (Mounicou et al, 2009), small metabolic products (metabolomics) (Dunn et al, 2008) and reactive electrophiles (adductomics) (Rubino et al, 2009;Li et al, in press). …”

Section: Moving Forwardmentioning

confidence: 99%

Implications of the exposome for exposure science

Rappaport

2010

J Expo Sci Environ Epidemiol

351

271

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During the 1920s, the forerunners of exposure science collaborated with health professionals to investigate the causes of occupational diseases. With the birth of U.S. regulatory agencies in the 1970s, interest in the environmental origins of human diseases waned, and exposure scientists focused instead upon levels of selected contaminants in air and water. In fact, toxic chemicals enter the body not only from exogenous sources (air, water, diet, drugs, and radiation) but also from endogenous processes, including inflammation, lipid peroxidation, oxidative stress, existing diseases, infections, and gut flora. Thus, even though current evidence suggests that non-genetic factors contribute about 90% of the risks of chronic diseases, we have not explored the vast majority of human exposures that might initiate disease processes. The concept of the exposome, representing the totality of exposures received by a person during life, encompasses all sources of toxicants and, therefore, offers scientists an agnostic approach for investigating the environmental causes of chronic diseases. In this context, it is appropriate to regard the ''environment'' as the body's internal chemical environment and to define ''exposures'' as levels of biologically active chemicals in this internal environment. To explore the exposome, it makes sense to employ a top-down approach based upon biomonitoring (e.g. blood sampling) rather than a bottom-up approach that samples air, water, food, and so on. Because sources and levels of exposure change over time, exposomes can be constructed by analyzing toxicants in blood specimens obtained during critical stages of life. Initial investigations could use archived blood from prospective cohort studies to measure important classes of toxic chemicals, notably, reactive electrophiles, metals, metabolic products, hormone-like substances, and persistent organic compounds. The exposome offers health scientists an avenue for integrating research that is currently fractured along lines related to particular diseases and risk factors, and can thereby promote discovery of the key exposures responsible for chronic diseases. By embracing the exposome as its operational paradigm, exposure science can play a major role in discovering and mitigating these exposures. Exposure science and the regulatory agendaMany of the endeavors we associate with exposure science originated in the first half of the 20th century when health scientists and engineers collaborated to construct exposureresponse relationships for occupational diseases. Methods for measuring airborne dusts and chemicals can be traced to surveys of mines and factories during the 1920s (see, e.g., (Greenburg and Smith, 1922;Greenburg, 1926)), and personal sampling was first applied in workplaces in 1960 (Sherwood and Greenhalgh, 1960). Early investigators sometimes employed both air and biological measurements to study tissue damage and toxicokinetics (see, e.g., (Smyth and Smyth, 1928;Roach, 1953Roach, , 1966). Studies of urban air pollutants were in...

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Section: Moving Forwardmentioning

confidence: 99%

Implications of the exposome for exposure science

Rappaport

2010

J Expo Sci Environ Epidemiol

351

271

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“…Overall, the above-mentioned papers document the feasibility and the effectiveness of a classic proteomic approach. Moreover, it is worth noting here that in the case of metallodrugs additional proteomic experiments may be devised that are centered on the metal and are principally aimed at investigating metal distribution patterns within the proteome (metallomics) [22][23][24]. These investigative approaches, relying on the selective tagging of the metallodrug or of the metal itself within 1D or 2D gels through highly sensitive methods, allow in principle the identification of all those proteins capable of binding the metallodrug of interest.…”

Section: Introductionmentioning

confidence: 99%

Exploring the biochemical mechanisms of cytotoxic gold compounds: a proteomic study

et al. 2010

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We have recently shown that a group of structurally diverse gold compounds are highly cytotoxic toward a panel of 36 human tumor cell lines through a variety of biochemical mechanisms. A classic proteomic approach is exploited here to gain deeper insight into those mechanisms. This investigation is focused on Auoxo6, a novel binuclear gold(III) complex, and auranofin, a clinically established gold(I) antiarthritic drug. First, the 72-h cytotoxicity profiles of Auoxo6 and auranofin were determined against A2780 human ovarian carcinoma cells. Subsequently, protein extraction from gold-treated A2780 cells sensitive to cisplatin and 2D gel electrophoresis separation were carried out according to established procedures. Notably, both metallodrugs caused relatively modest changes in protein expression in comparison with controls as only 11 out of approximately 1,300 monitored spots showed appreciable quantitative changes. Very remarkably, six altered proteins were in common between the two treatments. Eight altered proteins were identified by mass spectrometry; among them was ezrin, a protein associated with the cytoskeleton and involved in apoptosis. Interestingly, two altered proteins, i.e., peroxiredoxins 1 and 6, are known to play crucial roles in the cell redox metabolism. Increased cleavage of heterogeneous ribonucleoprotein H was also evidenced, consistent with caspase 3 activation. Overall, the results of the present proteomic study point out that the mode of action of Auoxo6 is strictly related to that of auranofin, that the induced changes in protein expression are limited and selective, that both gold compounds trigger caspase 3 activation and apoptosis, and that a few affected proteins are primarily involved in cell redox homeostasis.

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“…Detected Lys 3 , COOH], respectively. The fragmentation pathways were all in good agreement with the molecular structure of Met and the previous studies.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

Real Time Online Correction of Mass Shifts and Intensity Fluctuations in Extractive Electrospray Ionization Mass Spectrometry

Tian

Chen

et al. 2015

Anal. Chem.

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Real time online calibration of mass shift and intensity fluctuation to improve the accuracy of measurements for identification and quantitation in trace mass spectrometric analysis was demonstrated using extractive electrospray ionization mass spectrometry (EESI-MS). The signals of authentic compounds (e.g., lysine (Lys), proline (Pro), and histidine (His)) spiked into the extractive solution for the EESI process were used as the references to calibrate the signal of analytes (e.g., methionine (Met)) in the untreated sample solution. The intensity of the analyte signal was recorded simultaneously with the reference signals. The analyte signals at a given time point were calibrated on the basis of these correlation factors and real time signal response of the reference. The calibrated signal of Met at 10 μg L −1 was improved with a better signal-to-noise ratio (S/N from 2.3 to 4.3), better linearity (R 2 from 0.9758 to 0.9980), and reduced relative standard deviation (RSD from 9.8% to 6.0%). The shift of mass-to-charge ratio of Met signal between the detected and theoretical values was decreased from 247 ± 133 to −7 ± 167 ppm for 50 min of detection using a linear ion trap mass analyzer and was reduced from −0.27 ± 0.60 to −0.12 ± 0.23 ppm for 50 min of detection using an Orbitrap mass analyzer (P = 95%). This method has been validated using a certified standard amino acids solution (GBW(E)100062) and applied for quantitative detection of amino acids in chicken feed, urine, nutritional drink, and facial mask samples, showing that the method is useful to improve the accuracy of mass spectrometric analysis.

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Metallomics: the concept and methodology

Cited by 309 publications

References 115 publications

Implications of the exposome for exposure science

Implications of the exposome for exposure science

Exploring the biochemical mechanisms of cytotoxic gold compounds: a proteomic study

Real Time Online Correction of Mass Shifts and Intensity Fluctuations in Extractive Electrospray Ionization Mass Spectrometry

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