A heptameric peptide purified from Spirulina sp. gastrointestinal hydrolysate inhibits angiotensin I-converting enzyme- and angiotensin II-induced vascular dysfunction in human endothelial cells

Heo,Seong-Yeong; Ko,Seok-Chun; Kim,Chang  Su; Oh,Gun-Woo; Ryu,Bomi; Qian,Zhong‑Ji; Kim,Geunhyung; Park,Won  Sun; Choi,Il-Whan; Phan,Thi   Tuong Vy; Heo,Soo-Jin; Kang,Do-Hyung; Yi,Myunggi; Jung,Won-Kyo

doi:10.3892/ijmm.2017.2941

A heptameric peptide purified from Spirulina sp. gastrointestinal hydrolysate inhibits angiotensin I-converting enzyme- and angiotensin II-induced vascular dysfunction in human endothelial cells

Authors:
- Seong-Yeong Heo
- Seok-Chun Ko
- Chang Su Kim
- Gun-Woo Oh
- Bomi Ryu
- Zhong‑Ji Qian
- Geunhyung Kim
- Won Sun Park
- Il-Whan Choi
- Thi Tuong Vy Phan
- Soo-Jin Heo
- Do-Hyung Kang
- Myunggi Yi
- Won-Kyo Jung
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Affiliations: Department of Biomedical Engineering, and Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University, Busan 48513, Republic of Korea, Department of Orthopedic Surgery, Kosin University Gospel Hospital, Busan 49267, Republic of Korea, School of Pharmacy, The University of Queensland, Brisbane, QLD 4072, Australia, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang, Guangdong 524088, P.R. China, Department of Bio-Mechatronic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi 16419, Republic of Korea, Department of Physiology, Kangwon National University, School of Medicine, Chuncheon, Gangwon 24341, Republic of Korea, Department of Microbiology, Inje University College of Medicine, Busan 47392, Republic of Korea, Jeju International Marine Science Center for Research and Education, Korea Institute of Ocean Science and Technology (KIOST), Jeju 63349, Republic of Korea
Published online on: April 4, 2017 https://doi.org/10.3892/ijmm.2017.2941
Pages: 1072-1082
Copyright: © Heo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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