{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T17:04:31Z","timestamp":1774112671706,"version":"3.50.1"},"reference-count":51,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,2,25]],"date-time":"2019-02-25T00:00:00Z","timestamp":1551052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Institute of Fisheries Science","award":["R2019053"],"award-info":[{"award-number":["R2019053"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Enhanced oxidative stress plays a central role in promoting endothelial dysfunction, leading to the development of atherosclerosis. In this study, we investigated the protective effects of the hydrolysates derived from blue mussel (Mytilus edulis) against H2O2-mediated oxidative injury in human umbilical vein endothelial cells (HUVECs). The blue mussel hydrolysates were prepared by enzymatic hydrolysis with eight proteases, and blue mussel-\u03b1-chymotrypsin hydrolysate (BMCH) showed the highest antioxidant activities in DPPH radical scavenging, ABTS+ radical scavenging, and ORAC value compared to those of the other hydrolysates. BMCH also inhibited Cu2+-mediated low density lipoprotein (LDL) oxidation. Treatment of H2O2 resulted in the decreased HUVEC viability whereas pre-treatment with BMCH increased HUVEC viability and reduced reactive oxygen species (ROS) generation. BMCH pre-treatment increased cellular antioxidant capacities, including levels of glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) against H2O2-mediated oxidative stress in HUVECs. Flow cytometry and western blot analysis revealed that BMCH pre-treatment significantly reduced H2O2-mediated HUVEC apoptosis through inhibition of caspase-3 activation. Real-time-qPCR analysis showed that BMCH down-regulated expression of p53 and caspase-3 genes, as well as decreased the bax\/bcl-2 ratio. Taken together, these results indicate that BMCH may be useful as functional food ingredients for protecting endothelial dysfunction or related disease.<\/jats:p>","DOI":"10.3390\/md17020135","type":"journal-article","created":{"date-parts":[[2019,2,25]],"date-time":"2019-02-25T03:06:52Z","timestamp":1551064012000},"page":"135","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Amino Acid Composition, Antioxidant, and Cytoprotective Effect of Blue Mussel (Mytilus edulis) Hydrolysate through the Inhibition of Caspase-3 Activation in Oxidative Stress-Mediated Endothelial Cell Injury"],"prefix":"10.3390","volume":"17","author":[{"given":"Yunok","family":"Oh","sequence":"first","affiliation":[{"name":"Department of Marine-Bio Convergence Science, Pukyong National University, Busan 48547, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang-Bum","family":"Ahn","sequence":"additional","affiliation":[{"name":"Division of Food and Nutrition, Chonnam National University, Gwangju 61186, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ki-Ho","family":"Nam","sequence":"additional","affiliation":[{"name":"Food Safety and Processing Research Division, National Fisheries Research &amp; Development Institute, Busan 4608, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yeon-Kye","family":"Kim","sequence":"additional","affiliation":[{"name":"Food Safety and Processing Research Division, National Fisheries Research &amp; Development Institute, Busan 4608, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na Young","family":"Yoon","sequence":"additional","affiliation":[{"name":"Food Safety and Processing Research Division, National Fisheries Research &amp; Development Institute, Busan 4608, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae-Young","family":"Je","sequence":"additional","affiliation":[{"name":"Department of Marine-Bio Convergence Science, Pukyong National University, Busan 48547, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e146","DOI":"10.1161\/CIR.0000000000000485","article-title":"Heart disease and stroke statistics-2017 update: A report from the American Heart Association","volume":"135","author":"Benjamin","year":"2017","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1475-2840-5-4","article-title":"Endothelial dysfunction: A comprehensive appraisal","volume":"5","author":"Esper","year":"2006","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"222","DOI":"10.5830\/CVJA-2011-068","article-title":"Endothelial dysfunction: The early predictor of atherosclerosis","volume":"23","author":"Mudau","year":"2012","journal-title":"Cardiovasc. J. Afr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1056\/NEJMoa1109034","article-title":"Genetic associations with valvular calcification and aortic stenosis","volume":"368","author":"Thanassoulis","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_5","first-page":"40","article-title":"Pathogenesis of atherosclerosis: A multifactorial process","volume":"7","author":"Singh","year":"2002","journal-title":"Exp. Clin. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1161\/01.RES.87.10.840","article-title":"Endothelial dysfunction in cardiovascular diseases: The role of oxidant stress","volume":"87","author":"Cai","year":"2000","journal-title":"Circ. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1161\/01.ATV.0000051384.43104.FC","article-title":"Endothelial dysfunction: A marker of atherosclerotic risk","volume":"23","author":"Bonetti","year":"2003","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1191\/0961203305lu2216oa","article-title":"Oxidant stress, inflammation and atherogenesis","volume":"14","author":"Davi","year":"2005","journal-title":"Lupus"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"86","DOI":"10.4067\/S0716-97602000000200008","article-title":"Endothelial cell oxidative stress and signal transduction","volume":"33","author":"Foncea","year":"2000","journal-title":"Biol. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1002\/ana.410280122","article-title":"Atherosclerosis and stroke","volume":"28","author":"Taylor","year":"1990","journal-title":"Ann. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"C7","DOI":"10.1016\/j.jacc.2005.09.068","article-title":"Pathogenesis of atherosclerosis","volume":"47","author":"Falk","year":"2006","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"189","DOI":"10.2174\/13892037113149990041","article-title":"Marine bioactive peptides as potential antioxidants","volume":"14","author":"Ngo","year":"2013","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1021\/np0204038","article-title":"Marine natural products as novel antioxidant prototypes","volume":"66","author":"Takamatsu","year":"2003","journal-title":"J. Nat. Prod."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1007\/s12010-015-1689-9","article-title":"Overview of antioxidant peptides derived from marine resources: The sources, characteristic, purification, and evaluation methods","volume":"176","author":"Wu","year":"2015","journal-title":"Appl. Biochem. Biotechnol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1016\/j.foodres.2013.01.045","article-title":"Hepatoprotective effect of peptic hydrolysate from salmon pectoral fin protein byproducts on ethanol-induced oxidative stress in Sprague\u2013Dawley rats","volume":"51","author":"Je","year":"2013","journal-title":"Food Res. Int."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.foodchem.2017.09.043","article-title":"Blue mussel (Mytilus edulis) protein hydrolysate promotes mouse mesenchymal stem cell differentiation into osteoblasts through up-regulation of bone morphogenetic protein","volume":"242","author":"Hyung","year":"2018","journal-title":"Food Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1016\/j.peptides.2010.06.020","article-title":"Antioxidative peptides from food proteins: A review","volume":"31","author":"Sarmadi","year":"2010","journal-title":"Peptides"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1016\/j.foodchem.2012.12.002","article-title":"Purification and characterisation of a novel antioxidant peptide derived from blue mussel (Mytilus edulis) protein hydrolysate","volume":"138","author":"Wang","year":"2013","journal-title":"Food Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.jff.2015.10.023","article-title":"Partial purification and identification of three antioxidant peptides with hepatoprotective effects from blue mussel (Mytilus edulis) hydrolysate by peptic hydrolysis","volume":"20","author":"Park","year":"2016","journal-title":"J. Funct. Foods"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/j.bcp.2009.05.029","article-title":"A novel marine compound xyloketal B protects against oxidized LDL-induced cell injury in vitro","volume":"78","author":"Chen","year":"2009","journal-title":"Biochem. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"948","DOI":"10.3390\/md13020948","article-title":"Design and synthesis of novel xyloketal derivatives and their protective activities against H2O2-induced HUVEC injury","volume":"13","author":"Liu","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.jff.2014.09.007","article-title":"Protective effect of fucoxanthin isolated from Ishige okamurae against high-glucose induced oxidative stress in human umbilical vein endothelial cells and zebrafish model","volume":"11","author":"Kang","year":"2014","journal-title":"J. Funct. Foods"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.tcm.2013.12.001","article-title":"Oxidative stress and endothelial dysfunction: Clinical evidence and therapeutic implications","volume":"24","author":"Higashi","year":"2014","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Leiva, E., Wehinger, S., Guzm\u00e1n, L., and Orrego, R. (2015). Role of Oxidized LDL in Atherosclerosis. Hypercholesterolemia, InTech.","DOI":"10.5772\/59375"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1021\/acs.jafc.7b04036","article-title":"Rice Bioactive Peptide Binding with TLR4 To Overcome H2O2-Induced Injury in Human Umbilical Vein Endothelial Cells through NF-\u03baB Signaling","volume":"66","author":"Liang","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/1550-2783-2-2-38","article-title":"The antioxidant role of glutathione and N-acetyl-cysteine supplements and exercise-induced oxidative stress","volume":"2","author":"Kerksick","year":"2005","journal-title":"J. Int. Soc. Sports Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s11010-005-5075-8","article-title":"Overexpression of human GPX1 modifies Bax to Bcl-2 apoptotic ratio in human endothelial cells","volume":"277","author":"Faucher","year":"2005","journal-title":"Mol. Cell. Biochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1002\/(SICI)1097-4652(199811)177:2<324::AID-JCP14>3.0.CO;2-9","article-title":"Involvement of reactive oxygen species and caspase 3 activation in arsenite-induced apoptosis","volume":"177","author":"Chen","year":"1998","journal-title":"J. Cell. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1002\/jcp.10333","article-title":"Endothelial cell functions","volume":"196","author":"Michiels","year":"2003","journal-title":"J. Cell. Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"563","DOI":"10.12659\/MSM.899730","article-title":"Inhibition of hydrogen peroxide-induced human umbilical vein endothelial cells aging by allicin depends on Sirtuin1 activation","volume":"23","author":"Lin","year":"2017","journal-title":"Med. Sci. Monit."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e41","DOI":"10.1161\/ATVBAHA.117.309228","article-title":"Reactive oxygen species generation and atherosclerosis","volume":"37","author":"Nowak","year":"2017","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.pathophys.2006.05.002","article-title":"Oxidative stress and atherosclerosis","volume":"13","author":"Singh","year":"2006","journal-title":"Pathophysiology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S0002-9149(02)03144-2","article-title":"Role of oxidative stress in atherosclerosis","volume":"91","author":"Harrison","year":"2003","journal-title":"Am. J. Cardiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/ncpcardio1211","article-title":"Oxidative stress in vascular disease: Causes, defense mechanisms and potential therapies","volume":"5","year":"2008","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2988","DOI":"10.2174\/138161209789058093","article-title":"Oxidative stress, endothelial dysfunction and atherosclerosis","volume":"15","author":"Victor","year":"2009","journal-title":"Curr. Pharm. Des."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Petrulea, M., Muresan, A., and Duncea, I. (2012). Oxidative stress and antioxidant status in hypo-and hyperthyroidism. Antioxidant Enzyme, InTech.","DOI":"10.5772\/51018"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1093\/jn\/133.4.985","article-title":"Polyphenolic flavonoids differ in their antiapoptotic efficacy in hydrogen peroxide\u2013treated human vascular endothelial cells","volume":"133","author":"Choi","year":"2003","journal-title":"J. Nutr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1152\/nips.01519.2004","article-title":"Morphological features of cell death","volume":"19","author":"Ziegler","year":"2004","journal-title":"Physiology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2977","DOI":"10.1016\/j.bbamcr.2016.09.012","article-title":"Activation of apoptosis signalling pathways by reactive oxygen species","volume":"1863","year":"2016","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Cell Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1038\/38525","article-title":"A model for p53-induced apoptosis","volume":"389","author":"Polyak","year":"1997","journal-title":"Nature"},{"key":"ref_41","first-page":"1","article-title":"Abieslactone induces cell cycle arrest and apoptosis in human hepatocellular carcinomas through the mitochondrial pathway and the generation of reactive oxygen species","volume":"9","author":"Wang","year":"2014","journal-title":"PLoS ONE"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"9166","DOI":"10.1073\/pnas.93.17.9166","article-title":"Cellular oxidative stress and the control of apoptosis by wild-type p53, cytotoxic compounds, and cytokines","volume":"93","author":"Lotem","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"S656","DOI":"10.1016\/S0003-4975(02)04687-8","article-title":"The basic biology of apoptosis and its implications for cardiac function and viability","volume":"75","author":"Valen","year":"2003","journal-title":"Ann. Thorac. Surg."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Kuang, J., Yan, X., Genders, A.J., Granata, C., and Bishop, D.J. (2018). An overview of technical considerations when using quantitative real-time PCR analysis of gene expression in human exercise research. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0196438"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.biopha.2018.08.143","article-title":"Protective effect of enzymatic hydrolysates from seahorse (Hippocampus abdominalis) against H2O2-mediated human umbilical vein endothelial cell injury","volume":"108","author":"Oh","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/sj.cdd.4400476","article-title":"Emerging roles of caspase-3 in apoptosis","volume":"6","author":"Porter","year":"1999","journal-title":"Cell Death Differ."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"90","DOI":"10.4103\/1319-3767.61234","article-title":"Antioxidant enzyme activities in hepatic tissue from children with chronic cholestatic liver disease","volume":"16","author":"Ismail","year":"2010","journal-title":"Saudi J. Gastroenterol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"535","DOI":"10.3746\/jkfn.2009.38.5.535","article-title":"Extraction of polyphenols from apple peel using cellulase and pectinase and estimation of antioxidant activity","volume":"38","author":"Park","year":"2009","journal-title":"J. Korean Soc. Food Sci. Nutr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.foodchem.2008.09.033","article-title":"ORAC and TEAC assays comparison to measure the antioxidant capacity of food products","volume":"114","author":"Zulueta","year":"2009","journal-title":"Food Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/0304-4165(86)90300-4","article-title":"De novo synthesis of glutathione in human fibroblasts during in vitro ageing and in some metabolic diseases as measured by a flow cytometric method","volume":"883","author":"Poot","year":"1986","journal-title":"Biochim. Biophys. Acta (BBA) Gen. Subj."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/nprot.2008.73","article-title":"Analyzing real-time PCR data by the comparative C T method","volume":"3","author":"Schmittgen","year":"2008","journal-title":"Nat. Protoc."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/17\/2\/135\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:34:32Z","timestamp":1760186072000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/17\/2\/135"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,25]]},"references-count":51,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2019,2]]}},"alternative-id":["md17020135"],"URL":"https:\/\/doi.org\/10.3390\/md17020135","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,25]]}}}