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Proteomic study of endothelial dysfunction in response to homocysteinylated albumin

  • Reema Banarjee
  • Akshay Sharma
  • Shakuntala Bai
  • Arati Deshmukh
  • Mahesh KulkarniEmail author
Original Article
  • 12 Downloads

Abstract

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.

Graphic abstract

Keywords

Endothelial dysfunction Homocysteine Proteomics SWATH Chemical modification 

Abbreviations

BSA

Bovine serum albumin

ED

Endothelial dysfunction

HUVECs

Human umbilical vein endothelial cells

Hcy

Homocysteine

Hct

Homocysteine thiolactone

HHcy

Hyperhomocystenemia

SASPs

Senescence-associated secretory proteins

SWATH

Sequential window acquisition of theoretical masses

Notes

Acknowledgements

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.

Supplementary material

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Supplementary material 1 (PDF 119 kb)
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Supplementary material 2 (XLSX 17584 kb)
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Supplementary material 3 (XLSX 13 kb)
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Supplementary material 4 (XLSX 275 kb)

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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Reema Banarjee
    • 1
    • 2
  • Akshay Sharma
    • 1
  • Shakuntala Bai
    • 1
    • 2
  • Arati Deshmukh
    • 1
    • 2
  • Mahesh Kulkarni
    • 1
    • 2
    Email author
  1. 1.Proteomics Facility, Biochemical Sciences DivisionCSIR-National Chemical LaboratoryPuneIndia
  2. 2.Academy of Scientific and Innovative Research (AcSIR)GhaziabadIndia

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