THESIS
2016
xvii, 110 pages : illustrations (some color) ; 30 cm
Abstract
Biomarkers are characteristics that could be measured and evaluated as an indicator of
normal biological processes, pathogenic processes, or pharmacologic responses to a
therapeutic intervention. Complex organ function or cognizable changes in molecular level
can be used as biomarkers. Natural diseases and exposing to toxicants or specific
environments may lead to fatal alteration of the biological system of a subject. Detecting
alterations in the early stage, diseases could be treated appropriate. As a consequence, the
evaluation of health status is extremely useful in health care and medication. Biomarkers are
extremely useful in both toxicological research as well as biological monitoring.
Oxidative stress is related to the process of aging and many kinds of chronic disea...[
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Biomarkers are characteristics that could be measured and evaluated as an indicator of
normal biological processes, pathogenic processes, or pharmacologic responses to a
therapeutic intervention. Complex organ function or cognizable changes in molecular level
can be used as biomarkers. Natural diseases and exposing to toxicants or specific
environments may lead to fatal alteration of the biological system of a subject. Detecting
alterations in the early stage, diseases could be treated appropriate. As a consequence, the
evaluation of health status is extremely useful in health care and medication. Biomarkers are
extremely useful in both toxicological research as well as biological monitoring.
Oxidative stress is related to the process of aging and many kinds of chronic diseases. It
was caused by the accumulation of reactive oxygen/nitrogen species (ROS/RNS) broke the
imbalance between oxidants and antioxidants. Excess ROS/RNS will attack bimolecular and
generate formaldehyde in vivo. With formaldehyde being both ubiquitous in the ambient
environment and one of the most common reactive carbonyls produced from endogenous
metabolism, quantitating formaldehyde exposure is thus an essential way to risk assessments.
The goal of my first project is to develop thioproline (thiazolidine-4-carboxylic acid, TA), a
cysteine-conjugated metabolite of formaldehyde as a biomarker for assessing the risk of
oxidative stress and formaldehyde exposures. Dose-dependent formation of TA was observed in the cultured resuspension solution of Escherichia coli (E. coli) exposed to hydroxyl radical
mediators of Fe
2+-EDTA, H
2O
2, and NaOCl, indicating the potential use of TA as biomarker
of exposure to oxidative stress and disease risk.
Formaldehyde may also reacted with amino acid residues in protein leading to
post-translational modifications (PTMs) to proteins which have been well-documented to
play important roles in normal cell physiology such as cell signaling and protein functions.
PTMs have also been demonstrated to be one of the milestones in the pathophysiology of
many human diseases such as cancer, age-related pathology, and neurodegenerative
disorders. The goal of my second project is to identify of a novel PTM, 'thiazolidination',
formed by reacting formaldehyde with cysteine residue in protein. The study was
performed by quantitating thioproline in protein in formaldehyde- and oxidant-exposed E.
coli. Further, N
6-formyllysine, a well-defined formylation product formed by reacting
formaldehyde with lysine, was exploited in a comparative study to evaluate the relative
reactivity and amount of thiazolidination in the protein formylation chemistry. It is feasible
that 'thiazolidination' may serve a biomarker for oxidative stress exposure and with the
potential of filling one of the gaps in mining for unknown/novel PTMs in protein.
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