title: L-Cysteine supplementation reduces high-glucose and ketone-induced adhesion of monocytes to endothelial cells by inhibiting ROS.
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.
authors.affiliation: Department of Pediatrics, Louisiana State University Health Sciences Center, 1501 Kings Highway, P.O. Box 33932, Shreveport, LA, 71130, USA.
authors.forename: Preeti
authors.initials: P
authors.lastname: Kanikarla-Marie
authors.forename: Sushil K
authors.initials: SK
authors.lastname: Jain
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D003545:Cysteine / Q000494:pharmacology*; D019587:Dietary Supplements; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007659:Ketones / Q000494:pharmacology*; D008954:Models, Biological; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D007659:Ketones; D017382:Reactive Oxygen Species; D018799:Intercellular Adhesion Molecule-1; D005947:Glucose; D003545:Cysteine