Lactoferricin-Related Peptides with Inhibitory Effects on ACE-Dependent Vasoconstriction

Abstract

A selection of lactoferricin B (LfcinB)-related peptides with an angiotensin I-converting enzyme (ACE) inhibitory effect have been examined using in vitro and ex vivo functional assays. Peptides that were analyzed included a set of sequence-related antimicrobial hexapeptides previously reported and two representative LfcinB-derived peptides. In vitro assays using hippuryl-L-histidyl-L-leucine (HHL) and angiotensin I as substrates allowed us to select two hexapeptides, PACEI32 (Ac-RKWHFW-NH2) and PACEI34 (Ac-RKWLFW-NH2), and also a LfcinB-derived peptide, LfcinB17-31 (Ac-FKCRRWQWRMKKLGA-NH2). Ex vivo functional assays using rabbit carotid arterial segments showed PACEI32 (both D- and L-enantiomers) and LfcinB17-31 have inhibitory effects on ACE-dependent angiotensin I-induced contraction. None of the peptides exhibited in vitro ACE inhibitory activity using bradykinin as the substrate. In conclusion, three bioactive lactoferricin-related peptides exhibit inhibitory effects on both ACE activity and ACE-dependent vasoconstriction with potential to modulate hypertension that deserves further investigation.

Bovine lactoferrin pepsin hydrolysate exerts inhibitory effect on angiotensin I-converting enzyme-dependent vasoconstriction

“…We have reported previously that angiotensin I induces ACE-dependent vasoconstriction in the rabbit isolated carotid artery, as supported by the inhibition of angiotensin I-induced but not angiotensin II-induced contractions by the ACE inhibitor captopril (Centeno et al, 2006). In the present study, challenge of rabbit carotid arterial segments with depolarizing solution (KCl 50 mM) induced phasic contraction followed by active tone maintained until KCl washout (Fig.…”

“…LFH was assayed in vitro for its capacity to inhibit the ACE activity using hippuryl-L-histidyl-L-leucine (HHL; Sigma) as substrate and following the protocol described previously (Centeno et al, 2006). ACE (from porcine kidney) was purchased from Sigma.…”

“…Recently, we have demonstrated inhibitory effects on ACE activity and ACE-dependent vasoconstriction of synthetic Lfcin-related peptides including two representative LfcinB-derived peptides, LfcinB 20À25 and LfcinB 17À31 . We used an ex vivo model, the rabbit isolated carotid artery, in which angiotensin I induces ACE-dependent vasoconstriction checked by inhibition with the selective inhibitor captopril (Centeno et al, 2006). Local formation of angiotensin II from angiotensin I by ACE present in the arterial wall is necessary for induction of contraction by inactive angiotensin I (Egleme, Cressier, & Wood, 1990).…”

QSAR-aided in silico approach in evaluation of food proteins as precursors of ACE inhibitory peptides

“…Our study showed that lactoferrin, a well known protein for its diverse biological activities including antimicrobial, antiviral and antioxidant activities (Tomita, Wakabayashi, Yamauchi, Teraguchi, & Hayasawa, 2002), possesses the most potent peptides in milk including VRW, with a predicted IC 50 value of 0.6 μM ( Table 2). Lactoferricin-related peptides were reported to have ACE inhibitory activity (Centeno et al, 2006). It should be noted that lactoferricinrelated peptides are rich in hydrophobic and positively charged amino acid residues, which were postulated to play an important role in the potency of ACE inhibitory peptides.…”

Casein Fermentate of Lactobacillus animalis DPC6134 Contains a Range of Novel Propeptide Angiotensin-Converting Enzyme Inhibitors

“…ACE catalyzes the release of the dipeptide His-Leu from the angiotensin I C terminus, which results in the octapeptide angiotensin II, a potent vasoconstrictor (45). ACE also hydrolyzes and inactivates the vasoactive bradykinin (4). Additionally, ACE is a stimulant for the release of aldosterone in the adrenal cortex (6,7).…”