L-Cysteine supplementation reduces high-glucose and ketone-induced adhesion of monocytes to endothelial cells by inhibiting ROS

Mol Cell Biochem. 2014 Jun;391(1-2):251-6. doi: 10.1007/s11010-014-2009-3. Epub 2014 Mar 14.

Abstract

Type 1 diabetic (T1D) patients are hyperglycemic and also show elevated blood levels of ketone bodies, particularly acetoacetate (AA) and β-hydroxybutyrate (BHB). T1D patients have a greater risk of developing endothelial dysfunction and cardiovascular disease (CVD). Supplementation with cysteine-rich milk proteins has been shown to be beneficial in improving various biomarkers of endothelial dysfunction and CVD. This study examines whether L-cysteine (LC) per se prevents monocyte adhesion to endothelial cells, a critical step in endothelial dysfunction. Human umbilical vein endothelial cells and THP-1 monocytes were pretreated with and without LC (500 μM) for 2 h and then exposed to ketones (AA or BHB, 0-4 mM) and/or high glucose (HG) (25 mM) for 24 h. This study shows that LC reduces HG and ketone-induced ROS production, ICAM-1 expression, and the adhesion of monocytes to endothelial cells. This study provides a biochemical mechanism by which milk protein supplementation can be beneficial in preventing the excess endothelial dysfunction and CVD seen in diabetic patients.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Adhesion / drug effects
  • Cysteine / pharmacology*
  • Dietary Supplements
  • Endothelial Cells / cytology*
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Glucose / pharmacology*
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism
  • Ketones / pharmacology*
  • Models, Biological
  • Monocytes / cytology*
  • Monocytes / drug effects
  • Monocytes / metabolism
  • Reactive Oxygen Species / metabolism*

Substances

  • Ketones
  • Reactive Oxygen Species
  • Intercellular Adhesion Molecule-1
  • Glucose
  • Cysteine