A heptameric peptide purified from Spirulina sp gastrointestinal hydrolysate inhibits angiotensin I-converting enzymeand angiotensin II-induced vascular dysfunction in human endothelial cells
A heptameric peptide purified from Spirulina sp gastrointestinal hydrolysate inhibits angiotensin I-converting enzymeand angiotensin II-induced vascular dysfunction in human endothelial cells
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DOI：
10.3892/ijmm.2017.2941
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发表时间：
2017-05-01
影响因子：
5.4
通讯作者：
Jung, Won-Kyo
中科院分区：
文献类型：
--
作者：
Heo, Seong-Yeong;Ko, Seok-Chun;Jung, Won-Kyo
在这项研究中，使用胃肠道酶水解海洋微藻螺旋藻衍生的蛋白质，产生血管紧张素 I (Ang I) 转换酶 (ACE) 抑制肽。经过连续纯化后，有效的 ACE 抑制肽由 7 个氨基酸组成：Thr-Met-Glu-Pro-Gly-Lys-Pro（分子量，759 Da）。使用 Lineweaver-Burk 图和分子模型进行的分析表明，纯化的肽充当 ACE 的混合非竞争性抑制剂。还研究了该肽对 Ang II 诱导的血管功能障碍相关因子的细胞产生的抑制作用。在人内皮细胞中，用纯化的肽培养细胞时，Ang II 诱导的一氧化氮和活性氧的产生受到抑制，诱导型一氧化氮合酶 (iNOS) 和内皮素-1 (ET-1) 的表达下调。此外，该肽还能阻断 p38 丝裂原激活蛋白激酶的激活。这些结果表明，这种源自螺旋藻的肽值得进一步研究，作为 ACE 和血管功能障碍的潜在药理学抑制剂。
In this study, a marine microalga Spirulina sp.derived protein was hydrolyzed using gastrointestinal enzymes to produce an angiotensin I (Ang I)-converting enzyme (ACE) inhibitory peptide. Following consecutive purification, the potent ACE inhibitory peptide was composed of 7 amino acids, Thr-Met-Glu-Pro-Gly-Lys-Pro (molecular weight, 759 Da). Analysis using the Lineweaver-Burk plot and molecular modeling suggested that the purified peptide acted as a mixed non-competitive inhibitor of ACE. The inhibitory effects of the peptide against the cellular production of vascular dysfunction- related factors induced by Ang II were also investigated. In human endothelial cells, the Ang II-induced production of nitric oxide and reactive oxygen species was inhibited, and the expression of inducible nitric oxide synthase (iNOS) and endothelin-1 (ET-1) was downregulated when the cells were cultured with the purified peptide. Moreover, the peptide blocked the activation of p38 mitogen-activated protein kinase. These results indicated that this Spirulina sp.-derived peptide warrants further investigation as a potential pharmacological inhibitor of ACE and vascular dysfunction.