Cigarette smoking is a major risk factor for developing pulmonary and cardiovascular diseases as well as some forms of cancer. Understanding the mechanisms by which smoking contributes to disease remains a major research focus. Increased levels of carbonylated serum proteins are present in smokers; albumin is the major carbonylated protein in the bronchoalveolar lavage fluid of older smokers. We have investigated the susceptibility of human serum albumin (HSA) to α,β-unsaturated aldehyde-induced carbonylation when exposed to whole-phase cigarette smoke extract (CSE). Fluorescence studies with fluorescent probes showed depletion of HSA Cys34 free thiol and marked decrease of free Lys residues. Spectrophotometric and immunochemical carbonyl assays after carbonyl derivatization with 2,4-dinitrophenylhydrazine revealed the formation of covalent carbonyl adducts. Nanoscale capillary liquid chromatography and electrospray tandem mass spectrometry analysis detected acrolein and crotonaldehyde Michael adducts at Cys34, Lys525, Lys351, and His39 at all the CSE concentrations tested. Lys541 and Lys545 were also found to form a Schiff base with acrolein. The carbonyl scavenger drugs, hydralazine and pyridoxamine, partially prevented CSE-induced HSA carbonylation. Carbonylation of HSA associated with cigarette smoking might result in modifications of its antioxidant properties and transport functions of both endogenous and exogenous compounds.

Colombo, G., Aldini, G., Orioli, M., Giustarini, D., Gornati, R., Rossi, R., et al. (2010). Water-soluble α,β-unsaturated aldehydes of cigarette smoke induce carbonylation of human serum albumin. ANTIOXIDANTS & REDOX SIGNALING, 12(3), 349-364 [10.1089/ars.2009.2806].

Water-soluble α,β-unsaturated aldehydes of cigarette smoke induce carbonylation of human serum albumin

GIUSTARINI D;ROSSI, RANIERI;
2010

Abstract

Cigarette smoking is a major risk factor for developing pulmonary and cardiovascular diseases as well as some forms of cancer. Understanding the mechanisms by which smoking contributes to disease remains a major research focus. Increased levels of carbonylated serum proteins are present in smokers; albumin is the major carbonylated protein in the bronchoalveolar lavage fluid of older smokers. We have investigated the susceptibility of human serum albumin (HSA) to α,β-unsaturated aldehyde-induced carbonylation when exposed to whole-phase cigarette smoke extract (CSE). Fluorescence studies with fluorescent probes showed depletion of HSA Cys34 free thiol and marked decrease of free Lys residues. Spectrophotometric and immunochemical carbonyl assays after carbonyl derivatization with 2,4-dinitrophenylhydrazine revealed the formation of covalent carbonyl adducts. Nanoscale capillary liquid chromatography and electrospray tandem mass spectrometry analysis detected acrolein and crotonaldehyde Michael adducts at Cys34, Lys525, Lys351, and His39 at all the CSE concentrations tested. Lys541 and Lys545 were also found to form a Schiff base with acrolein. The carbonyl scavenger drugs, hydralazine and pyridoxamine, partially prevented CSE-induced HSA carbonylation. Carbonylation of HSA associated with cigarette smoking might result in modifications of its antioxidant properties and transport functions of both endogenous and exogenous compounds.
Colombo, G., Aldini, G., Orioli, M., Giustarini, D., Gornati, R., Rossi, R., et al. (2010). Water-soluble α,β-unsaturated aldehydes of cigarette smoke induce carbonylation of human serum albumin. ANTIOXIDANTS & REDOX SIGNALING, 12(3), 349-364 [10.1089/ars.2009.2806].
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11365/412282