Novel antihypertensive lactoferrin-derived peptides produced by Kluyveromyces marxianus: gastrointestinal stability profile and in vivo angiotensin I-converting enzyme (ACE) inhibition.
Novel antihypertensive peptides released by Kluyveromyces marxianus from bovine lactoferrin (LF) have been identified. K. marxianus LF permeate was fractionated by semipreparative high performance liquid chromatography and 35 peptides contained in the angiotensin I-converting enzyme (ACE)-inhibitory fractions were identified by using an ion trap mass spectrometer. On the basis of peptide abundance and common structural features, six peptides were chemically synthesized. Four of them (DPYKLRP, PYKLRP, YKLRP, and GILRP) exerted in vitro inhibitory effects on ACE activity and effectively decreased systolic blood pressure after oral administration to spontaneously hypertensive rats (SHRs). Stability against gastrointestinal enzymes suggested that the sequence LRP could contribute to the in vivo effects of parental peptides. Finally, there were reductions in circulating ACE activity and angiotensin II level in SHRs after either DPYKLRP or LRP intake, thus confirming ACE inhibition as the in vivo mechanism for their antihypertensive effect.
Departamento de Biotecnología de Alimentos, Instituto de Agroquímica y Tecnología de Alimentos, Consejo Superior de Investigaciones Científicas (IATA-CSIC), Avenida Agustín Escardino 7, 46980 Paterna, Valencia, Spain.
Aurora
A
García-Tejedor
Laura
L
Sánchez-Rivera
María
M
Castelló-Ruiz
Isidra
I
Recio
Juan B
JB
Salom
Paloma
P
Manzanares
D000284:Administration, Oral; D000595:Amino Acid Sequence; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D001711:Biotransformation; D001794:Blood Pressure / Q000187:drug effects; D002417:Cattle; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D007716:Kluyveromyces / Q000378:metabolism*; D007781:Lactoferrin / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D010455:Peptides; D007703:Peptidyl-Dipeptidase A; D007781:Lactoferrin