Journal Home > Volume 10 , Issue 6
Nano Research 2017, 10(6): 1912-1923 https://doi.org/10.1007/s12274-016-1375-4
Research Article | Issue | Published: 05 January 2017

Biocompatibility of iron carbide and detection of metals ions signaling proteomic analysis via HPLC/ESI-Orbitrap

Show Author's Information Murtaza Hasan1,  Wenlong Yang1,  Yanmin Ju1,  Xin Chu1,  Yun Wang2,  Yulin Deng2,  Nasir Mahmood1,  Yanglong Hou1( )
Department of Materials Science and Engineering College of Engineering Peking University Beijing 100871 China
School of Life Sciences Beijing Institute of Technology Beijing 100081 China
Keywords:
biocompatibility, magnetic nanoparticles, 18O labeling, proteomic analysis
Cite this article:
Hasan M, Yang W, Ju Y, et al. Biocompatibility of iron carbide and detection of metals ions signaling proteomic analysis via HPLC/ESI-Orbitrap. Nano Research, 2017, 10(6): 1912-1923. https://doi.org/10.1007/s12274-016-1375-4
Download citation
EndNote(RIS)
BibTeX

579

Views

12

Downloads

Citations

37

Crossref

N/A

WoS

40

Scopus

0

CSCD

Abstract Full text Electronic supplementary material About this article

Recently, magnetic nanoparticles (NPs) have been extensively used in food industry and biomedical treatments. However, the biocompatibility mechanism on expression proteomics, before consideration of magnetic NPs for clinical application, has not yet been fully elucidated. Therefore, this study was undertaken to identify potential biomarkers of metal ion signaling proteins in human cervical cancer cell line (HeLa) cells. Here, we report the in vitro investigations of the cell cycle response and significant changes in protein abundance of HeLa cells when exposed to self-tailored hydrophilic Fe2C NPs. The comparative proteomic approach based on 18O labeling coupled with high performance liquid chromatography/electrospray ionization with ion trap mass analyzer (HPLC/ESI-Orbitrap) was applied, and 394 proteins were identified. There were 46 significantly differentiated proteins based on the specific metal ion signaling response. Among them, 60S ribosomal protein L37a, serine/arginine-rich splicing factor 7, calmodulin, and calumenin were downregulated, whereas transketolase was overexpressed. Functional interaction network of Fe2C-regulated proteins was successfully created by the STRING algorithm to show the strong interactions between proteins. This work will not only help to understand the molecular mechanism of metal ion signaling proteins that can potentially be used to develop therapeutic protocols for diagnosis of diseases but also give direction for tailoring biocompatible magnetic NPs.


menu
Abstract
Full text
Outline
Electronic supplementary material
About this article

Biocompatibility of iron carbide and detection of metals ions signaling proteomic analysis via HPLC/ESI-Orbitrap

Show Author's information Murtaza Hasan1, Wenlong Yang1, Yanmin Ju1, Xin Chu1, Yun Wang2, Yulin Deng2, Nasir Mahmood1, Yanglong Hou1( )
Department of Materials Science and Engineering College of Engineering Peking University Beijing 100871 China
School of Life Sciences Beijing Institute of Technology Beijing 100081 China

Abstract

Recently, magnetic nanoparticles (NPs) have been extensively used in food industry and biomedical treatments. However, the biocompatibility mechanism on expression proteomics, before consideration of magnetic NPs for clinical application, has not yet been fully elucidated. Therefore, this study was undertaken to identify potential biomarkers of metal ion signaling proteins in human cervical cancer cell line (HeLa) cells. Here, we report the in vitro investigations of the cell cycle response and significant changes in protein abundance of HeLa cells when exposed to self-tailored hydrophilic Fe2C NPs. The comparative proteomic approach based on 18O labeling coupled with high performance liquid chromatography/electrospray ionization with ion trap mass analyzer (HPLC/ESI-Orbitrap) was applied, and 394 proteins were identified. There were 46 significantly differentiated proteins based on the specific metal ion signaling response. Among them, 60S ribosomal protein L37a, serine/arginine-rich splicing factor 7, calmodulin, and calumenin were downregulated, whereas transketolase was overexpressed. Functional interaction network of Fe2C-regulated proteins was successfully created by the STRING algorithm to show the strong interactions between proteins. This work will not only help to understand the molecular mechanism of metal ion signaling proteins that can potentially be used to develop therapeutic protocols for diagnosis of diseases but also give direction for tailoring biocompatible magnetic NPs.

Keywords: biocompatibility, magnetic nanoparticles, 18O labeling, proteomic analysis

References(37)

1

Ray, P. C.; Yu, H. T.; Fu, P. P. Toxicity and environmental risks of nanomaterials: Challenges and future needs. J. Environ. Sci. Health C Environ. Carcinog. Ecotoxicol. Rev. 2009, 27, 1–35.
DOI Google Scholar
2

Ji, Z. X.; Jin, X.; George, S.; Xia, T.; Meng, H.; Wang, X.; Suarez, E.; Zhang, H. Y.; Hoek, E. M. V.; Godwin, H. et al. Dispersion and stability optimization of TiO2 nanoparticles in cell culture media. Environ. Sci. Technol. 2010, 44, 7309–7314.
DOI Google Scholar
3

Hao, R.; Yu, J.; Ge, Z. G.; Zhao, L. Y.; Sheng, F. G.; Xu, L. L.; Li, G. J.; Hou, Y. L. Developing Fe3O4 nanoparticles into an efficient multimodality imaging and therapeutic probe. Nanoscale 2013, 5, 11954–11963.
DOI Google Scholar
5

Yu, J.; Hao, R.; Sheng, F. G.; Xu, L. L.; Li, G. J.; Hou, Y. L. Hollow manganese phosphate nanoparticles as smart multifunctional probes for cancer cell targeted magnetic resonance imaging and drug delivery. Nano Res. 2012, 5, 679–694.
DOI Google Scholar
6

Le Guével, X.; Spies, C.; Daum, N.; Jung, G.; Schneider, M. Highly fluorescent silver nanoclusters stabilized by glutathione: A promising fluorescent label for bioimaging. Nano Res. 2012, 5, 379–387.
DOI Google Scholar
7

Davydov, V.; Rakhmanina, A.; Kireev, I.; Alieva, I.; Zhironkina, O.; Strelkova, O.; Dianova, V.; Samani, T. D.; Mireles, K.; Yahia, L. H. et al. Solid state synthesis of carbon encapsulated iron carbide nanoparticles and their interaction with living cells. J. Mater. Chem. B 2014, 2, 4250–4261.
DOI Google Scholar
8

Shang, L.; Dörlich, R. M.; Trouillet, V.; Bruns, M.; Nienhaus, G. U. Ultrasmall fluorescent silver nanoclusters: Protein adsorption and its effects on cellular responses. Nano Res. 2012, 5, 531–542.
DOI Google Scholar
9

Chu, X.; Yu, J.; Hou, Y. L. Surface modification of magnetic nanoparticles in biomedicine. Chin. Phys. B 2015, 24, 014701.
DOI Google Scholar
10

Hao, R.; Xing, R. J.; Xu, Z. C.; Hou, Y. L.; Gao, S.; Sun, S. H. Synthesis, functionalization, and biomedical applications of multifunctional magnetic nanoparticles. Adv. Mater. 2010, 22, 2729–2742.
DOI Google Scholar
11

Mahmoudi, M.; Azadmanesh, K.; Shokrgozar, M. A.; Journeay, W. S.; Laurent, S. Effect of nanoparticles on the cell life cycle. Chem. Rev. 2011, 111, 3407–3432.
DOI Google Scholar
12

Thomson, A. J.; Gray, H. B. Bio-inorganic chemistry. Curr. Opin. Chem. Biol. 1998, 2, 155–158.
DOI Google Scholar
13

Waldron, K. J.; Robinson, N. J. How do bacterial cells ensure that metalloproteins get the correct metal? Nat. Rev. Microbiol. 2009, 7, 25–35.
DOI Google Scholar
14

Carver, P. L. Metal ions and infectious diseases. An overview from the clinic. In Interrelations between Essential Metal Ions and Human Diseases; Sigel, A.; Sigel, H.; Sigel, R. K. O., Eds.; Springer: Netherlands, 2013; pp 1-28.
Google Scholar
15

Verano-Braga, T.; Miethling-Graff, R.; Wojdyla, K.; Rogowska-Wrzesinska, A.; Brewer, J. R.; Erdmann, H.; Kjeldsen, F. Insights into the cellular response triggered by silver nanoparticles using quantitative proteomics. ACS Nano 2014, 8, 2161–2175.
DOI Google Scholar
16

Hofmann, D.; Tenzer, S.; Bannwarth, M. B.; Messerschmidt, C.; Glaser, S. F.; Schild, H.; Landfester, K.; Mailänder, V. Mass spectrometry and imaging analysis of nanoparticle- containing vesicles provide a mechanistic insight into cellular trafficking. ACS Nano 2014, 8, 10077–10088.
DOI Google Scholar
17

Yang, Z. Y.; Zhao, T. S.; Huang, X. X.; Chu, X.; Tang, T. Y.; Ju, Y. M.; Wang, Q.; Hou, Y. L.; Gao, S. Modulating the phases of iron carbide nanoparticles: From a perspective of interfering with the carbon penetration of Fe@Fe3O4 by selectively adsorbed halide ions. Chem. Sci. , in press, DOI: 10.1039/c6sc01819j.
DOI Google Scholar
18

Iqbal, J.; Li, W.; Hasan, M.; Li, Y. J.; Ullah, K.; Yun, W.; Awan, U.; Qing, Q.; Deng, Y. L. Distortion of homeostatic signaling proteins by simulated microgravity in rat hypothalamus: A16O/18O-labeled comparative integrated proteomic approach. Proteomics 2014, 14, 262–273.
DOI Google Scholar
19

Yu, J.; Yang, C.; Li, J. D. S.; Ding, Y. C.; Zhang, L.; Yousaf, M. Z.; Lin, J.; Pang, R.; Wei, L. B.; Xu, L. L. et al. Multifunctional Fe5C2 nanoparticles: A targeted theranostic platform for magnetic resonance imaging and photoacoustic tomography-guided photothermal therapy. Adv. Mater. 2014, 26, 4114–4120.
DOI Google Scholar
20

Pacheco-Palencia, L. A.; Mertens-Talcott, S.; Stephen, T. T. Chemical composition, antioxidant properties, and thermal stability of a phytochemical enriched oil from Açai (Euterpe oleracea Mart. ). J. Agric. Food Chem. 2008, 56, 4631–4636.
DOI Google Scholar
21

Del Signore, A.; Romeo, F.; Giaccio, M. Content of phenolic substances in basidiomycetes. Mycol. Res. 1997, 101, 552–556.
DOI Google Scholar
22

Lee, Y. S.; Kang, Y. H.; Jung, J. Y.; Lee, S.; Ohuchi, K.; Shin, K. H.; Kang, I. J.; Park, J. H.; Shin, H. K.; Lim, S. S. Protein glycation inhibitors from the fruiting body of phellinus linteus. Biol. Pharm. Bull. 2008, 31, 1968–1972.
DOI Google Scholar
23

Monopoli, M. P.; Åberg, C.; Salvati, A.; Dawson, K. A. Biomolecular coronas provide the biological identity of nanosized materials. Nat. Nanotechnol. 2012, 7, 779–786.
DOI Google Scholar
24

Oberdörster, G.; Stone, V.; Donaldson, K. Toxicology of nanoparticles: A historical perspective. Nanotoxicology 2007, 1, 2–25.
DOI Google Scholar
25

Tsang, W. Y.; Spektor, A.; Luciano, D. J.; Indjeian, V. B.; Chen, Z.; Salisbury, J. L.; Sánchez, I.; Dynlacht, B. D. CP110 cooperates with two calcium-binding proteins to regulate cytokinesis and genome stability. Mol. Biol. Cell 2006, 17, 3423–3434.
DOI Google Scholar
26

Reichow, S. L.; Clemens, D. M.; Freites, J. A.; Németh-Cahalan, K. L.; Heyden, M.; Tobias, D. J.; Hall, J. E.; Gonen, T. Allosteric mechanism of water-channel gating by Ca2+-calmodulin. Nat. Struct. Mol. Biol. 2013, 20, 1085–1092.
DOI Google Scholar
27

Jung, E. H.; Takeuchi, T.; Nishino, K.; Itokawa, Y. Studies on the nature of thiamine pyrophosphate binding and dependency on divalent cations of transketolase from human erythrocytes. Int. J. Biochem. 1988, 20, 1255–1259.
DOI Google Scholar
28

Sax, C. M.; Kays, W. T.; Salamon, C.; Chervenak, M. M.; Xu, Y. S.; Piatigorsky, J. Transketolase gene expression in the cornea is influenced by environmental factors and developmentally controlled events. Cornea 2000, 19, 833–841.
DOI Google Scholar
29

Stevens, F. C. Calmodulin: An introduction. Can. J. Biochem. Cell Biol. 1983, 61, 906–910.
DOI Google Scholar
30

Chin, D.; Means, A. R. Calmodulin: A prototypical calcium sensor. Trends Cell Biol. 2000, 10, 322–328.
DOI Google Scholar
31

Iqbal, J.; Li, W.; Hasan, M.; Liu, K. F.; Awan, U.; Saeed, Y.; Zhang, Y. Q.; Khan, A. M.; Shah, A.; Qing, H. et al. Differential expression of specific cellular defense proteins in rat hypothalamus under simulated microgravity induced conditions: Comparative proteomics. Proteomics 2014, 14, 1424–1433.
DOI Google Scholar
32

Iqbal, J.; Li, W.; Ullah, K.; Hasan, M.; Linna, G.; Awan, U.; Zhang, Y. Q.; Batool, S.; Qing, H.; Deng, Y. L. Study of rat hypothalamic proteome by HPLC/ESI ion trap and HPLC/ESI-Q-TOF MS. Proteomics 2013, 13, 2455–2468.
DOI Google Scholar
33

Chou, J. J.; Li, S. P.; Klee, C. B.; Bax, A. Solution structure of Ca2+-calmodulin reveals flexible hand-like properties of its domains. Nat. Struct. Biol. 2001, 8, 990–997.
DOI Google Scholar
34

Yabe, D.; Taniwaki, M.; Nakamura, T.; Kanazawa, N.; Tashiro, K.; Honjo, T. Human calumenin gene (CALU): cDNA isolation and chromosomal mapping to 7q32. Genomics 1998, 49, 331–333.
DOI Google Scholar
35

Marygold, S. J.; Coelho, C. M.; Leevers, S. J. Genetic analysis of RpL38 and RpL5, two minute genes located in the centric heterochromatin of chromosome 2 of drosophila melanogaster. Genetics 2005, 169, 683–695.
DOI Google Scholar
36

Li, X.; Manley, J. L. Inactivation of the SR protein splicing factor ASF/SF2 results in genomic instability. Cell 2005, 122, 365–378.
DOI Google Scholar
37

Krainer, A. R.; Conway, G. C.; Kozak, D. The essential pre-mRNA splicing factor SF2 influences 5' splice site selection by activating proximal sites. Cell 1990, 62, 35–42.
DOI Google Scholar
38

Lin, S. R.; Xiao, R.; Sun, P. Q.; Xu, X. D.; Fu, X. D. Dephosphorylation-dependent sorting of SR splicing factors during mRNP maturation. Mol. Cell 2005, 20, 413–425.
DOI Google Scholar
File
nr-10-6-1912_ESM.pdf (2.2 MB)
Publication history
Copyright
Acknowledgements

Publication history

Received: 27 June 2016
Revised: 12 November 2016
Accepted: 15 November 2016
Published: 05 January 2017
Issue date: June 2017

Copyright

© Tsinghua University Press and Springer-Verlag Berlin Heidelberg 2016

Acknowledgements

Acknowledgements

This work was supported in part by the Research Fellowship for International Young Scientists of the National Natural Science Foundation of China (Nos. 51550110502 and 51450110437), National Natural Science Foundation of China (Nos. 81421004, 51672010, and 51590882), NSFC/RGC Joint Research Scheme (No. 51361165201), and Opening Project of Beijing National Laboratory for Molecular Science. The authors thank the mass spectrometry facility of National Center for Protein Sciences at Peking University and Dr. Wen Zhou for assistance with LC-MS analysis.

Return