Abstract

Antihypertensive peptides (AHTPs) are a group of small peptides with the main role to block key enzymes or receptors in the angiotensin genesis pathway. A great number of AHTPs have been isolated or digested from natural food resources; however, comprehensive studies on comparisons of AHTPs in various species from the perspective of big data are rare. Here, we established a simplified local AHTP database, and performed in situ mapping for high throughput identification of AHTPs with high antihypertensive activity from high-quality whole proteome datasets of 18 fish species. In the 35 identified AHTPs with reported high activity, we observed that Gly-Leu-Pro, Leu-Pro-Gly, and Val-Ser-Val are the major components of fish proteins, and AHTP hit numbers in various species demonstrated a similar distributing pattern. Interestingly, Atlantic salmon (Salmo salar) is in possession of far more abundant AHTPs compared with other fish species. In addition, collagen subunit protein is the largest group with more matching AHTPs. Further exploration of two collagen subunits (col4a5 and col8a1) in more fish species suggested that the hit pattern of these conserved proteins among teleost is almost the same, and their phylogeny is consistent with the evolution of these fish species. In summary, our present study provides basic information for the relationship of AHTPs with fish proteins, which sheds light on rapid discovery of marine drugs or food additives from fish protein hydrolysates to alleviate hypertension.

Highlights

  • The prevalence of cardiovascular diseases is mainly caused by high blood pressure [1,2].Clinical trials have observed that lowering systolic blood pressure would reduce cardiovascular morbidity and mortality significantly [3]

  • We found that Atlantic salmon has more antihypertensive peptides (AHTPs) hits than other fish species

  • Since the AHTP hit number of every protein in each fish species (Figures 3c and S5) supported supported a variety of matched AHTPs for the numerous mapped proteins, we summarized the a variety of matched AHTPs for the numerous mapped proteins, we summarized the categories of 50 categories of 50 proteins with top hits and top scores for reference (Figure 4 and Figure S6)

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Summary

Introduction

The prevalence of cardiovascular diseases is mainly caused by high blood pressure [1,2]. Clinical trials have observed that lowering systolic blood pressure would reduce cardiovascular morbidity and mortality significantly [3]. Serious side effects, such as kidney function deterioration and electrolyte abnormalities, occurred with utilization of various antihypertensive medication [3,4]. Angiotensin converting enzyme (ACE) inhibitors are preferred antihypertensive drugs [5], as ACE is responsible for the conversion of angiotensin I (Ang I) into vasoconstrictor angiotensin II (Ang II) and the inactivation of vasodilator bradykinin [6,7]. Given the adverse effects of synthetic drugs, there is a growing demand for antihypertensive agents from natural food resources over the past decades since the discovery of natural antihypertensive peptides (AHTPs) from a snake venom [8,9]

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