Kanikarla-Marie Preeti, Jain Sushil K
Department of Pediatrics, Louisiana State University Health Sciences Center, 1501 Kings Highway, P.O. Box 33932, Shreveport, LA, 71130, USA.
Mol Cell Biochem. 2014 Jun;391(1-2):251-6. doi: 10.1007/s11010-014-2009-3. Epub 2014 Mar 14.
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.
1型糖尿病（T1D）患者血糖过高，血液中酮体水平也会升高，尤其是乙酰乙酸（AA）和β-羟基丁酸（BHB）。T1D患者发生内皮功能障碍和心血管疾病（CVD）的风险更高。已证明补充富含半胱氨酸的乳蛋白有助于改善内皮功能障碍和CVD的各种生物标志物。本研究探讨L-半胱氨酸（LC）本身是否能阻止单核细胞黏附于内皮细胞，这是内皮功能障碍的关键步骤。将人脐静脉内皮细胞和THP-1单核细胞分别用或不用LC（500μM）预处理2小时，然后暴露于酮类物质（AA或BHB，0 - 4 mM）和/或高糖（HG）（25 mM）中24小时。本研究表明，LC可减少HG和酮类物质诱导的活性氧生成、细胞间黏附分子-1（ICAM-1）表达以及单核细胞与内皮细胞的黏附。本研究提供了一种生化机制，通过该机制补充乳蛋白有助于预防糖尿病患者出现的过度内皮功能障碍和CVD。
