Download Biomolecules carbonylation in oxidative stress related human

Biomolecules carbonylation in oxidative
stress related human diseases
»
Dr. Maria Fedorova
Keywords
Lipid carbonylation
Lipid derived reactive carbonyls
are characterized by large variety of species with different physicochemical properties. New high
throughput analytical methods for
sensitive and specific detection of
lipid peroxidation products were
developed and allowed simultaneous detection of different types of
carbonyls using shotgun- and LCMS-based lipidomics approach.
 Oxidative stress related
human disorders
 Protein and lipid oxidation
 Carbonyl stress
Protein carbonylation
Protein carbonylation results either
from direct oxidation of amino
acid residues or from the reaction
between proteins and secondary
products of glycation and lipidperoxidation. Detection of carbonyated proteins in vivo is challenged
by their extremely low abundance.
New method utilizing MS-based enrichment was developed and tested
for specific detection of carbonylated proteins in complex biological
samples. Additionally combination
of oxolipidomics and proteomics
techniques allow to map adducts
between proteins and lipid peroxidation products.
Contact
Selected References
Dr. Maria Fedorova
Bioanalytics
UNIVERSITÄT LEIPZIG
BOLLINENI, R. C.; HOFFMANN, R.; FEDOROVA, M.
Identification of protein carbonylation sites by tow-dimensional liquid chromatography in
combination with MALDI- and ESI-MS. J Proteomics. 74 (2011), 2338–2350.
FEDOROVA, M.; KULEVA, N.; HOFFMANN, R.
Identification, quantification and functional aspects of skeletal muscle protein-carbonylation
in vivo during acute oxidative stress. J. Proteome Res. 9 (2010), 2516–2526.
FEDOROVA, M.; TODOROVSKY, T.; KULEVA, N.; HOFFMANN, R.
Quantitative evaluation of tryptophan oxidation in actin and troponin I from skeletal
muscles using a rat model of acute oxidative stress. Proteomics 10 (2010), 2696–2700.
Fakultät für Chemie und Mineralogie
Institut für Bioanalytische Chemie
Biotechnologisch-Biomedizinisches
Zentrum
Deutscher Platz 5
04103 Leipzig
fon +49 341 97-31336
fax +49 341 97-31339
[email protected]
PROTEIN ENGINEERING AND BIOANALYTICS
Carbonyl stress
Oxidative stress (OS) related human disorders, such as diabetes,
obesity, metabolic syndrome and
neurodegeneration, are characterized by elevated levels of oxidatively modified biomolecules (protein, lipids and DNA). Oxidation
of biomolecules results in numerous functional dysfunctions associated with disease progression.
One of the most abundant and
hazardous class of modifications
are reactive carbonyls (aldehydes,
ketones), which are considered as
a major hallmark of OS-related
diseases. Accumulation of reactive aldehydes and ketones leads
to carbonyl stress, which is characterized by high in vivo toxicity due
to protein aggregation, membrane
disruption and mutagenesis. Sensitive and specific detection of carbonyls as well as determination of
pathological threshold (control vs
disease) will facilitate identification
of prognostic biomarkers and development of preventive therapies.