4.6 Article

Plasma albumin cysteinylation is regulated by cystathionine β-synthase

Journal

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 325, Issue 4, Pages 1449-1453

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2004.10.191

Keywords

plasma albumin; ischemia; reperfusion; homocysteine; cysteine; multi-organ failure; cystathionine beta-synthase

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High homocysteine (Hey) levels are a well-known independent risk factor for endothelial damage in atherosclerosis. We examined whether a rat intestinal model of ischemia-reperfusion was associated with high Hey and with the modification of plasma albumin into cysteinylated species (CysAlb). The three treatment groups were as follows: midline abdominal incision (group A, n = 10), followed by ligation of the superior mesenteric artery for a period of 2 It (group B, n = 3), and followed by reperfusion for 1 h (group C, n = 10). Hey levels were 2.5-fold higher in group C than group A (p < 0.05). 100% and 73.44 +/- 0.04% of Alb were modified into Cys species in groups C and B, respectively, compared to 51.2% in group A. A cystathionine beta-synthase (CBS) deficient mouse model, known to have high plasma Hey levels, was also used to determine the extent of CysAlb. Hey levels, %CysAlb, and %HcyAlb were 180.1 +/- 45.7 muM, 0%, and 23.4 +/- 4.4% in CBS deficient mice, while in control mice, those values were 5.7 +/- 1.8 muM, 24.2 +/- 4.1%, and 0%, respectively (p < 0.05). High CysAlb and Hey levels were observed in a rat model of bowel ischemia/reperfusion while high HcyAlb and Hey levels with no CysAlb were observed in the CBS deficient mice. CysAlb may serve as a biomarker for the severity of gut ischemia, and high Hey may explain endothelial damage associated with this model. Additionally, active CBS is essential for the formation of CysAlb. (C) 2004 Elsevier Inc. All rights reserved.

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