Lin Cong, Zhang Li-Jun, Li Bo, Zhang Feng, Shen Qing-Rong, Kong Guo-Qing, Wang Xiao-Fan, Cui Shou-Hong, Dai Rong, Cao Wen-Qiang, Zhang Pu
Department of Cardiology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Neurology, People's Hospital of Linyi Affiliated to Qingdao University, Linyi, China.
Front Physiol. 2020 Jul 9;11:791. doi: 10.3389/fphys.2020.00791. eCollection 2020.
Hyperglycemia is the main feature of diabetes and may increase the risk of vascular calcification (VC), which is an independent predictor for cardiovascular and cerebrovascular diseases (CCD). Selenium (Se) may decrease the risk of CCD, and previous studies confirmed that Se-containing protein from Se-enriched platensis (Se-SP) exhibited novel antioxidant potential. However, the effect of Se-SP against VC has been not investigated. Herein, the protective effect and underlying mechanism of Se-SP against high glucose-induced calcification in mouse aortic vascular smooth muscle cells (MOVAS) were explored. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) results showed time-dependent uptake of Se-SP in MOVAS cells, which significantly inhibited high glucose-induced abnormal proliferation. Se-SP co-treatment also effectively attenuated high glucose-induced calcification of MOVAS cells, followed by decreased activity and expression of alkaline phosphatase (ALP). Further investigation revealed that Se-SP markedly prevented reactive oxygen species (ROS)-mediated DNA damage in glucose-treated MOVAS cells. ROS inhibition by glutathione (GSH) effectively inhibited high glucose-induced calcification, indicating that Se-SP could act as ROS inhibitor to inhibit high glucose-induced DNA damage and calcification. Moreover, Se-SP dramatically attenuated high glucose-induced dysfunction of mitogen-activated protein kinases (MAPKs) and phosphatidylinositol-3-kinase/AKT (PI3K/AKT) pathways. Se-SP after Se addition achieved enhanced potential in inhibiting high glucose-induced calcification, which validated that Se-SP as a new Se species could be a highly effective treatment for human CCD.
高血糖是糖尿病的主要特征，可能会增加血管钙化（VC）的风险，而血管钙化是心血管和脑血管疾病（CCD）的独立预测指标。硒（Se）可能会降低患CCD的风险，先前的研究证实，富硒钝顶螺旋藻中的含硒蛋白（Se-SP）具有新的抗氧化潜力。然而，Se-SP对VC的影响尚未得到研究。在此，我们探讨了Se-SP对高糖诱导的小鼠主动脉血管平滑肌细胞（MOVAS）钙化的保护作用及其潜在机制。电感耦合等离子体原子发射光谱（ICP-AES）结果显示，MOVAS细胞对Se-SP的摄取呈时间依赖性，这显著抑制了高糖诱导的异常增殖。Se-SP联合处理也有效减轻了高糖诱导的MOVAS细胞钙化，随后碱性磷酸酶（ALP）的活性和表达降低。进一步研究表明，Se-SP显著预防了葡萄糖处理的MOVAS细胞中活性氧（ROS）介导的DNA损伤。谷胱甘肽（GSH）抑制ROS有效抑制了高糖诱导的钙化，表明Se-SP可作为ROS抑制剂来抑制高糖诱导的DNA损伤和钙化。此外，Se-SP显著减轻了高糖诱导的丝裂原活化蛋白激酶（MAPKs）和磷脂酰肌醇-3-激酶/蛋白激酶B（PI3K/AKT）信号通路功能障碍。添加硒后的Se-SP在抑制高糖诱导的钙化方面具有增强的潜力，这证实了Se-SP作为一种新的硒物种可能是治疗人类CCD的高效药物。
