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

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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.

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Acknowledgments

The authors thank Georgia Morgan for excellent editing. The authors are supported by NIDDK and the ODS (RO1 DK072433), the Malcolm Feist Chair in Diabetes, and the Malcolm Feist Predoctoral Fellowship by the Institute for Cardiovascular Diseases and Imaging.

Conflicts of interest

No conflicts of interest are declared by the authors.

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Authors and Affiliations

  1. Department of Pediatrics, Louisiana State University Health Sciences Center, 1501 Kings Highway, P.O. Box 33932, Shreveport, LA, 71130, USA

    Preeti Kanikarla-Marie & Sushil K. Jain

  2. Department Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA, 71130, USA

    Preeti Kanikarla-Marie & Sushil K. Jain

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  1. Preeti Kanikarla-Marie
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Correspondence to Sushil K. Jain.

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Kanikarla-Marie, P., Jain, S.K. l-Cysteine supplementation reduces high-glucose and ketone-induced adhesion of monocytes to endothelial cells by inhibiting ROS. Mol Cell Biochem 391, 251–256 (2014). https://doi.org/10.1007/s11010-014-2009-3

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  • DOI: https://doi.org/10.1007/s11010-014-2009-3

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