Mass Spectrometric Characterization of Human Hemoglobin Adducts Formed in Vitro by Hexahydrophthalic Anhydride

Kristiansson, Monica H.; Jönsson, Bo; Lindh, Christian

doi:10.1021/tx0155911

Cited by 13 publications

(26 citation statements)

References 18 publications

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“…Tetrahydrophtalic anhydride (THPA) yields adducts with albumin (Kristiansson, Lindh, & Jonsson Bo, 2003;Kristiansson, Lindh, & Jonsson, 2004) and hemoglobin (Jonsson Bo, Lindh, & Welinder, 1997;Lindh & Jonsson Bo, 1998;Kristiansson, Ajonsson, & Lindh, 2002). The main attachment site was found to be the e-amino group of lysine side chains and the modified amino acid could be isolated from an enzymic digest of hemoglobin with trypsin followed by the unspecific protease pronase E and characterized by fragment ion analysis (Kristiansson, Ajonsson, & Lindh, 2002).…”

Section: Reaction With Chemical Sensitizersmentioning

confidence: 99%

“…The main attachment site was found to be the e-amino group of lysine side chains and the modified amino acid could be isolated from an enzymic digest of hemoglobin with trypsin followed by the unspecific protease pronase E and characterized by fragment ion analysis (Kristiansson, Ajonsson, & Lindh, 2002). A large number of lysine residues of HSA is modified in vitro at 10-fold molar excess of anhydride, while at 0.1-fold only a few positions yielded adducts, the main one being Lys 212 of subdomain IIA (Sennbro et al, 2003).…”

Section: Reaction With Chemical Sensitizersmentioning

confidence: 99%

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Toward an “omic” physiopathology of reactive chemicals: Thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds

Rubino

Pitton

Fabio

et al. 2009

Mass Spectrometry Reviews

109

170

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Cancer and degenerative diseases are major causes of morbidity and death, derived from the permanent modification of key biopolymers such as DNA and regulatory proteins by usually smaller, reactive molecules, present in the environment or generated from endogenous and xenobiotic components by the body's own biochemical mechanisms (molecular adducts). In particular, protein adducts with organic electrophiles have been studied for more than 30 [see, e.g., Calleman et al., 1978] years essentially for three purposes: (a) as passive monitors of the mean level of individual exposure to specific chemicals, either endogenously present in the human body or to which the subject is exposed through food or environmental contamination; (b) as quantitative indicators of the mean extent of the individual metabolic processing which converts a non-reactive chemical substance into its toxic products able to damage DNA (en route to cancer induction through genotoxic mechanisms) or key proteins (as in the case of several drugs, pesticides or otherwise biologically active substances); (c) to relate the extent of protein modification to that of biological function impairment (such as enzyme inhibition) finally causing the specific health damage. This review describes the role that contemporary mass spectrometry-based approaches employed in the qualitative and quantitative study of protein-electrophile adducts play in the discovery of the (bio)chemical mechanisms of toxic substances and highlights the future directions of research in this field. A particular emphasis is given to the measurement of often high levels of the protein adducts of several industrial and environmental pollutants in unexposed human populations, a phenomenon which highlights the possibility that a number of small organic molecules are generated in the human organism through minor metabolic processes, the imbalance of which may be the cause of "spontaneous" cases of cancer and of other degenerative diseases of still uncharacterized etiology. With all this in mind, it is foreseen that a holistic description of cellular functions will take advantage of new analytical methods based on time-integrated metabolomic measurements of a new biological compartment, the "adductome," aimed at better understanding integrated organism response to environmental and endogenous stressors.

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Section: Reaction With Chemical Sensitizersmentioning

confidence: 99%

Section: Reaction With Chemical Sensitizersmentioning

confidence: 99%

Toward an “omic” physiopathology of reactive chemicals: Thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds

Rubino

Pitton

Fabio

et al. 2009

Mass Spectrometry Reviews

109

170

View full text Add to dashboard Cite

show abstract

“…HHP acid was then quantified on an LC/MS/MS (API 3000; Applied Biosystems, Foster City, CA, USA) coupled to an HPLC system from Perkin-Elmer (Norwalk, CT, USA) as described by Kristiansson et al (2002). Briefly, samples were analyzed on a C 18 column (2.1 mm i.d.…”

Section: Quantification Of Hhp Acid By Lc/ms/msmentioning

confidence: 99%

“…After an acid hydrolysis of the protein adducts, the corresponding HHP acid is released. The HHP acid can then be analysed using liquid chromatography tandem MS (LC/MS/MS; Kristiansson et al, 2002) or after derivatization using gas chromatography mass spectrometry (GC/MS; Lindh and Jönsson, 1998).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of an immunoaffinity extraction column for enrichment of adducts between human serum albumin and hexahydrophthalic anhydride in plasma

Johannesson

Kristiansson

Jönsson

et al. 2007

Biomedical Chromatography

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An immunoaffinity extraction (IAE) column was prepared for extraction of adducts between human serum albumin (HSA) and hexahydrophthalic anhydride (HHPA). HHPA is a strong sensitizer inducing immunoglobulin E antibodies in vivo. Polyclonal antibodies from a rabbit immunized with keyhole limpet hemocyananin-HHPA conjugate were purified using a Protein A Sepharose gel. To obtain antibodies with optimal affinity towards HHPA-protein adducts, HHPA-specific antibodies were selected using an N-hydroxysuccinimide-Sepharose column coupled with albumin-HHPA conjugate. Antibodies eluted from this column at pH 2.2 were selected to prepare the IAE column. The column was evaluated using 2 mL plasma spiked with HSA-HHPA conjugate. The column was eluted with glycine buffer at pH 2.0. The conjugates in the eluate were hydrolyzed to the corresponding HHP acid and quantified by mass spectrometry. The average recovery of HHPA adducts in 11 experiments was 68% with a coefficient of variation (CV) of 7%. The column's capacity to bind protein-HHPA adducts was found to be linear in the range of 0.15-1.2 nmol conjugate. The evaluation showed that the IAE column had adequate affinity towards the HHPA adducts and that the adducts could be extracted with good recovery and precision from a large volume of plasma.

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“…It has previously been shown that Hb adducts can be used as long-term biomarkers of sensitizing compounds [17,18]. Protein adducts formed by sensitizing chemicals have been characterized in several studies [17,[19][20][21][22][23] using LC/MS/MS or GC/MS. However, the identity of covalent binding sites of acrylates in proteins has not previously been studied.…”

Section: Introductionmentioning

confidence: 99%

Identification of covalent binding sites of ethyl 2-cyanoacrylate, methyl methacrylate and 2-hydroxyethyl methacrylate in human hemoglobin using LC/MS/MS techniques

Jeppsson

Mörtstedt

Ferrari

et al. 2010

Journal of Chromatography B

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Mass Spectrometric Characterization of Human Hemoglobin Adducts Formed in Vitro by Hexahydrophthalic Anhydride

Cited by 13 publications

References 18 publications

Toward an “omic” physiopathology of reactive chemicals: Thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds

Toward an “omic” physiopathology of reactive chemicals: Thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds

Evaluation of an immunoaffinity extraction column for enrichment of adducts between human serum albumin and hexahydrophthalic anhydride in plasma

Identification of covalent binding sites of ethyl 2-cyanoacrylate, methyl methacrylate and 2-hydroxyethyl methacrylate in human hemoglobin using LC/MS/MS techniques

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