title: A heptameric peptide purified from Spirulina sp. gastrointestinal hydrolysate inhibits angiotensin I-converting enzyme- and angiotensin II-induced vascular dysfunction in human endothelial cells.
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.
authors.affiliation: Department of Biomedical Engineering, and Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University, Busan 48513, Republic of Korea.
authors.forename: Seong-Yeong
authors.initials: SY
authors.lastname: Heo
authors.affiliation: Department of Biomedical Engineering, and Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University, Busan 48513, Republic of Korea.
authors.forename: Seok-Chun
authors.initials: SC
authors.lastname: Ko
authors.affiliation: Department of Orthopedic Surgery, Kosin University Gospel Hospital, Busan 49267, Republic of Korea.
authors.forename: Chang Su
authors.initials: CS
authors.lastname: Kim
authors.affiliation: Department of Biomedical Engineering, and Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University, Busan 48513, Republic of Korea.
authors.forename: Gun-Woo
authors.initials: GW
authors.lastname: Oh
authors.affiliation: School of Pharmacy, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Bomi
authors.initials: B
authors.lastname: Ryu
authors.affiliation: College of Food Science and Technology, Guangdong Ocean University, Zhanjiang, Guangdong 524088, P.R. China.
authors.forename: Zhong-Ji
authors.initials: ZJ
authors.lastname: Qian
authors.affiliation: Department of Bio-Mechatronic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi 16419, Republic of Korea.
authors.forename: Geunhyung
authors.initials: G
authors.lastname: Kim
authors.affiliation: Department of Physiology, Kangwon National University, School of Medicine, Chuncheon, Gangwon 24341, Republic of Korea.
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
authors.affiliation: Department of Microbiology, Inje University College of Medicine, Busan 47392, Republic of Korea.
authors.forename: Il-Whan
authors.initials: IW
authors.lastname: Choi
authors.affiliation: Department of Biomedical Engineering, and Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University, Busan 48513, Republic of Korea.
authors.forename: Thi Tuong Vy
authors.initials: TT
authors.lastname: Phan
authors.affiliation: Jeju International Marine Science Center for Research and Education, Korea Institute of Ocean Science and Technology (KIOST), Jeju 63349, Republic of Korea.
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Heo
authors.affiliation: Jeju International Marine Science Center for Research and Education, Korea Institute of Ocean Science and Technology (KIOST), Jeju 63349, Republic of Korea.
authors.forename: Do-Hyung
authors.initials: DH
authors.lastname: Kang
authors.affiliation: Department of Biomedical Engineering, and Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University, Busan 48513, Republic of Korea.
authors.forename: Myunggi
authors.initials: M
authors.lastname: Yi
authors.affiliation: Department of Biomedical Engineering, and Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University, Busan 48513, Republic of Korea.
authors.forename: Won-Kyo
authors.initials: WK
authors.lastname: Jung
mesh_terms: D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001665:Binding Sites; D001808:Blood Vessels / Q000187:drug effects* / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008958:Models, Molecular; D008970:Molecular Weight; D009569:Nitric Oxide / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D017382:Reactive Oxygen Species / Q000378:metabolism; D053545:Spirulina / Q000378:metabolism
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D010455:Peptides; D017382:Reactive Oxygen Species; D000804:Angiotensin II; D009569:Nitric Oxide; D020928:Mitogen-Activated Protein Kinases; D007703:Peptidyl-Dipeptidase A