Cytoprotective Peptides from Blue Mussel Protein Hydrolysates: Identification and Mechanism Investigation in Human Umbilical Vein Endothelial Cells Injury.

Indyaswan Tegar Suryaningtyas,Chang-Bum Ahn,Jae-Young Je

doi:10.3390/md19110609

Indyaswan Tegar Suryaningtyas, Chang-Bum Ahn + Show 1 more

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https://doi.org/10.3390/md19110609

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Abstract

Cardiovascular disease represents a leading cause of mortality and is often characterized by the emergence of endothelial dysfunction (ED), a physiologic condition that takes place in the early progress of atherosclerosis. In this study, two cytoprotective peptides derived from blue mussel chymotrypsin hydrolysates with the sequence of EPTF and FTVN were purified and identified. Molecular mechanisms underlying the cytoprotective effects against oxidative stress which lead to human umbilical vein endothelial cells (HUVEC) injury were investigated. The results showed that pretreatment of EPTF, FTVN and their combination (1:1) in 0.1 mg/mL significantly reduced HUVEC death due to H2O2 exposure. The cytoprotective mechanism of these peptides involves an improvement in the cellular antioxidant defense system, as indicated by the suppression of the intracellular ROS generation through upregulation of the cytoprotective enzyme heme oxygenase-1. In addition, H2O2 exposure triggers HUVEC damage through the apoptosis process, as evidenced by increased cytochrome C release, Bax protein expression, and the elevated amount of activated caspase-3, however in HUVEC pretreated with peptides and their combination, the presence of those apoptotic stimuli was significantly decreased. Each peptide showed similar cytoprotective effect but no synergistic effect. Taken together, these peptides may be especially important in protecting against oxidative stress-mediated ED.

Highlights

The imbalance between the antioxidant defense mechanism and reactive oxygen species (ROS) generation in a physiological system leads to oxidative stress and associated disease consequences
Cytoprotective peptides were purified from α-chymotrypsin-assisted protein hydrolysates of blue mussel by a cytoprotective activity-guided purification process
The F3 fraction that showed the highest protective effect on human umbilical vein endothelial cells (HUVEC) against H2 O2 -induced oxidative cell damage was selected and further purified by HPLC equipped with a C18 column (Figure 1)

Summary

Introduction

The imbalance between the antioxidant defense mechanism and reactive oxygen species (ROS) generation in a physiological system leads to oxidative stress and associated disease consequences. When the mitochondrial membrane potential is reduced, a series of signaling proteins is activated, which leads to the activation of several stress-responsive genes, such as p53, Bax, Bcl-2, and caspase-3 [1]. This results in enhanced reactive oxygen species generation, severe cell damage, and apoptosisinduced cell death [2,3]. These risk factors can induce endothelial dysfunction (ED) through a variety of processes [4,5]. ED is considered as an early indicator in the progression of cardiovascular disease (CVD) [6,7]

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