Astaxanthin alleviates oxidative stress insults-related derangements in human vascular endothelial cells exposed to glucose fluctuations

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• 作者：Lobna A. Abdelzaher ; Takahiro Imaizumi ; Tokiko Suzuki ; Kengo Tomita ; Michinori Takashina ; Yuichi Hattori ; ^{yhattori@med.u-toyama.ac.jp" class="auth_mail" title="E-mail the corresponding author}
• 关键词：CM-H2DCFPA ; 5-(and-6)-chloromethyl-2&prime ; 7&prime ; -dichlorofluorescein diacetate ; eNOS ; endothelial nitric oxide synthase ; ERK ; extracellular signal-regulated protein kinase ; GAPDH ; glyceraldehyde-3-phosphate dehydrogenase ; HUVEC ; human umbilical venous endothelial cell ; ICAM-1 ; intercellular adhesion molecule-1 ; JNK ; c-Jun N-terminal kinase ; IL-6 ; interleukin-6 ; MAPK ; mitogen-activated protein kinase ; Mn-SOD ; manganese-dependent superoxide dismutase ; NAC ; N-acetyl-L-cysteine ; NO ; nitric oxide
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：1 April 2016
• 年：2016
• 卷：150
• 期：Complete
• 页码：24-31
• 全文大小：942 K

文摘

Glycemic fluctuations may play a critical role in the pathogenesis of diabetic complications, such as cardiovascular disease. We investigated whether the oxycarotenoid astaxanthin can reduce the detrimental effects of fluctuating glucose on vascular endothelial cells. Human umbilical venous endothelial cells were incubated for 3 days in media containing 5.5 mM glucose, 22 mM glucose, or 5.5 mM glucose alternating with 22 mM glucose in the absence or presence of astaxanthin or N-acetyl-L-cysteine (NAC). Constant high glucose increased reactive oxygen species (ROS) generation, but such an effect was more pronounced in fluctuating glucose. This was associated with up-regulated p22^phox expression and down-regulated peroxisome proliferator activated receptor-γ coactivator (PGC-1α) expression. Astaxanthin inhibited ROS generation, p22^phox up-regulation, and PGC-1α down-regulation by the stimuli of glucose fluctuation. Fluctuating glucose, but not constant high glucose, significantly decreased the endothelial nitric oxide synthase (eNOS) phosphorylation level at Ser-1177 without affecting total eNOS expression, which was prevented by astaxanthin as well as by the anti-oxidant NAC. Transferase-mediated dUTP nick end labeling (TUNEL) showed increased cell apoptosis in fluctuating glucose. Glucose fluctuation also resulted in up-regulating gene expression of pro-inflammatory mediators, interleukin-6 and intercellular adhesion molecule-1. These adverse changes were subdued by astaxanthin. The phosphorylation levels of c-Jun N-terminal kinase (JNK) and p38 were significantly increased by glucose fluctuations, and astaxanthin significantly inhibited the increase in JNK and p38 phosphorylation. Taken together, our results suggest that astaxanthin can protect vascular endothelial cells against glucose fluctuation by reducing ROS generation.