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

Mar Drugs. 2019 Feb 25;17(2):135. doi: 10.3390/md17020135.

Abstract

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-α-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.

Keywords: bioactive peptide; blue mussel; caspase-3 activation; endothelial dysfunction; oxidative stress.

MeSH terms

  • Amino Acids / chemistry*
  • Amino Acids / metabolism
  • Amino Acids / pharmacology
  • Animals
  • Antioxidants / chemistry
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Caspase 3 / metabolism*
  • Enzyme Activation / drug effects
  • Glutathione / metabolism
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / pathology
  • Humans
  • Hydrogen Peroxide / administration & dosage
  • Lipoproteins, LDL / metabolism
  • Mytilus edulis / chemistry*
  • Mytilus edulis / metabolism
  • Oxidative Stress / drug effects*
  • Protein Hydrolysates / chemistry
  • Protein Hydrolysates / isolation & purification
  • Protein Hydrolysates / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger
  • Reactive Oxygen Species / metabolism
  • Tumor Suppressor Protein p53 / metabolism
  • bcl-2-Associated X Protein / metabolism

Substances

  • Amino Acids
  • Antioxidants
  • BCL2 protein, human
  • Lipoproteins, LDL
  • Protein Hydrolysates
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Reactive Oxygen Species
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • Hydrogen Peroxide
  • CASP3 protein, human
  • Caspase 3
  • Glutathione