Proteomic study of endothelial dysfunction in response to homocysteinylated albumin
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Hyperhomocysteinemia is reported to be involved in the progression of cardiovascular and neurological diseases. The levels of homocysteine in blood can increase due to deficiency of folic acid, vitamin B12, or B6. Homocyteine gets converted to its cyclic analog, homocysteine thiolactone, by methionyl-tRNA synthetase during the process of translation, which can further react with the free amino groups of proteins forming an N-homocysteinylated product. The homocysteine-modified proteins have altered structure and function and can be deleterious to cells. Accumulation of such modified proteins in plasma could be one of the possible mechanisms for the development of cardiovascular complications in patients with hyperhomocysteinemia. To investigate this, albumin was modified with homocysteine thiolactone, and its effect on endothelial function was studied in Human Umbilical Vein Endothelial Cells (HUVECs) by SWATH MS-based proteomics approach. Treatment of HUVECs with homocysteinylated albumin for 24 h negatively affected cell viability, and led to altered abundance of about 53 proteins, out of the total 1410 identified in proteomic analysis. Thus, homocysteinylated proteins can lead to dysfunction in vascular endothelial cells and predispose to cardiovascular diseases.
KeywordsEndothelial dysfunction Homocysteine Proteomics SWATH Chemical modification
Bovine serum albumin
Human umbilical vein endothelial cells
Senescence-associated secretory proteins
Sequential window acquisition of theoretical masses
This work was carried out under the project BSC0124. The authors acknowledge University Grants Commission for research fellowship.
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest.
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