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New study investigates the interaction of thimerosal with proteins

(14.12.2008)


Background:
Thimerosal (THI, also called thiomersal)) is a mercury-containing compound used as preservative in vaccines and other drugs in concentrations up to 100 mg L-1. Especially in multi-dose ampullae its antibacterial and antifungal properties is meant to prevent microbial contamination during repeated removal of single doses. Already  introduced in 1931, Thimerosal never went through extensive safety evaluation. Due to suspected neurotoxic effects Thimerosal has been banned in the European Union in 2001.  However, THI is still in use in the US and in developing countries. Current discussions about the toxicity of THI and other organomercury compounds are either centred around effects like autism or the exact functions of molecular mimicry, by which mercury species are suspected to be actively transported in the human body.

The new study:
The research group from the University of Münster, Germany used reversed phase liquid chromatography (LC) hyphenated with either inductively coupled plasma mass spectrometry (ICP-MS) or electrospray mass spectrometry (ESI-MS) detection for studying the interaction of thimerosal with free thiols in proteins. ß-lactoglobulin A (18.4 kDa) from bovine milk and human serum albumin (66.5 kDa) have been used as model substances under conditions mimicking physiological conditions upon an intravenous injection of thimerosal-containing drugs. The results obtained clearly proved the formation of ethylmercury–protein adducts in both cases. 

Using tryptic digestion of ß-lactoglobulin A, the binding site of ethylmercury, a free thiol residue in the peptide T13, could be identified. For future work the researchers hope to obtain data with even more relevance to physiological processes by using systems with increasing similarity to human blood, including natural levels of cysteine and glutathione, which are also present in human blood in significant concentrations.

The work will appear in the first issue of the new Journal Metallomics, to be published January 2009.


The new study

Stefan Trümpler, Wiebke Lohmann, Björn Meermann, Wolfgang Buscher, Michael Sperling, Uwe Karst, Interaction of Thimerosal with Proteins - Ethylmercury Adduct Formation of Human Serum Albumin and b-Lactoglobulin A, Metallomics, 1/1 (2009). doi: 10.139/b815978e


Related studies

S.C. Fang, E. Fallin, The binding of various mercurial compounds to serum proteins, Bull. Environ. Contam. Toxicol., 15 (1976) 110-117. doi: 10.1007/BF01686202

Akira Yasutake, Kimiko Hirayama, Masayasu Inoue, Interaction of methylmercury compounds with albumin, Arch. Toxicol., 64 (1990) 639-643. doi: 10.1007/BF01974691   

Ruth E. Hoffmeyer, Satya P. Singh, Christian J. Doonan, Andrew R. S. Ross,
Richard J. Hughes, Ingrid J. Pickering, Graham N. George, Molecular Mimicry in Mercury Toxicology, Chem. Res. Toxicol., 19 (2006) 753-759. doi: 10.1021/tx0503449

Ruth E. Hoffmeyer, Satya P. Singh, Christian J. Doonan, Ingrid J. Pickering, Graham N. George, More on Molecular Mimicry in Mercury Toxicology, Chem. Res. Toxicol., 19 (2006) 1118-1120. DOI: 10.1021/tx060177s

 Christy C. Bridges, Rudolfs K. Zalups, Molecular Mimicry as a Mechanism for the Uptake of Cysteine S-Conjugates of Methylmercury and Inorganic Mercury, Chem. Res. Toxicol., 19 (2006) 1117-1118. DOI: 10.1021/tx060158i

 Yan Li, Yan Jiang, Xiu-Ping Yan, Probing Mercury Species-DNA Interactions by Capillary Electrophoresis with On-Line Electrothermal Atomic Absorption Spectrometric Detection, Anal. Chem., 78/17 (2006) 6115-6120. DOI: 10.1021/ac060644a

Grazyna Zareba, Elsa Cernichiari, Rieko Hojo, Scott Mc Nitt, Bernard Weiss, Moiz M. Mumtaz, Dennis E. Jones, Thomas W. Clarkson, Thimerosal distribution and metabolism in neonatal mice: comparison with methyl mercury, J. Appl. Toxicol., 27/5 (2007) 511-518. doi: 10.1002/jat.1272g

 Yan Li, Xiu-Ping Yan, Chen Chen, Yun-Long Xia, Yan Jiang, Human serum albumin-mercurial species interactions, J. Proteome Res., 6/6 (2007) 2277-2286. doi: 10.1021/pr0700403

 Xing Wu, Hong Liang, Kimberley A. O'Hara, Jack C. Yalowich, Brian B. Hasinoff, Thiol-modulated mechanisms of the cytotoxicity of thimerosal and inhibition of DNA topoisomerase II alpha, Chem. Res. Toxicol., 21/2 (2008) 483-493. doi: 10.1021/tx700341n

 Eva M. Krupp, Bruce F. Milne, Adrien Mestrot, Andrew A. Meharg, Jörg Feldmann, Investigation into mercury bound to biothiols: structural identification using ESI-ion-trap MS and introduction of a method for their HPLC separation with simultaneous detection by ICP-MS and ESI-MS, Anal. Bioanal. Chem., 390/7 (2008) 1753-1764. doi: 10.1007/s00216-008-1927-x

Yifei Guo, Liqin Chen, Limin Yang, Qiuquan Wang, Counting Sulfhydryls and Disulfide Bonds in Peptides and Proteins Using Mercurial Ions as an MS-Tag, J. Am. Soc. Mass Spectrom., 19/8 (2008) 1108-1113. doi:10.1016/j.jasms.2008.05.005


Related EVISA Resources
    
EVISA Journals Database: Metallomics
EVISA Journals Database: Journals related to metallomics
EVISA Link Database: Toxicity of Thimerosal
 EVISA Link Database: All About Thimerosal
EVISA News Section: News related to Thimerosal
EVISA Summary page: ESI-MS: The tool for the identification of species
EVISA Summary page: LC-ICP-MS - The most often used hyphenated system for speciation analysis


Related News

EVISA News, October 30, 2008: Precautionary approach to methylmercury needed
EVISA News, July 10, 2008: Methyl mercury metabolism in man influenced by genetic factors
EVISA News, Januar 12, 2008: New California study concludes that thimerosal seems not to be the major cause for autism
EVISA News, November 16, 2006: A silent pandemic: Industrial chemicals are impairing the brain development of children worldwide
EVISA News, March 24, 2006: Mercury Containing Preservative Alters Immune Function
EVISA News, April 27, 2005: New results about toxicity of thimerosal
EVISA News, February 11, 2005: New findings about Thimerosal Neurotoxicity
 

last time modified: December 14, 2008









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