Peptides from Lactobacillus hydrolysates of bovine milk caseins inhibit prolyl-peptidases of human colon cells.
Prolyl-rich peptides derived from hydrolysates of bovine caseins have been previously shown to inhibit angiotensin converting enzyme (ACE) activity, suggesting that they may also be able to inhibit the enzymatic activities of prolyl-specific peptidases. This study shows that peptides derived from α(S1)-casein and β-casein inhibited the enzymatic activities of purified recombinant matrix metalloprotease (MMP)-2, MMP-7, and MMP-9. The inhibitory efficacy was sequence-dependent. These peptides also selectively inhibited the enzymatic activities of prolyl-amino-peptidases, prolyl-amino-dipeptidases, and prolyl-endopeptidases in extracts of HT-29 and SW480 human colon carcinoma cells, but not in intact cells. They were not cytotoxic or growth inhibitory for these cells. Thus, the prolyl-rich selected peptides were good and selective inhibitors of MMPs and post-proline-cleaving proteases, demonstrating their potential to control inadequate proteolytic activity in the human digestive tract, without inducing cytotoxic effects.
University Institute of Pathology, Centre Hospitalier Universitaire Vaudois (CHUV), and University of Lausanne (UNIL), Lausanne, Switzerland. lucienne.juillerat@chuv.ch
Lucienne
L
Juillerat-Jeanneret
Marie-Claude
MC
Robert
Marcel A
MA
Juillerat
D000595:Amino Acid Sequence; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002364:Caseins / Q000737:chemistry / Q000378:metabolism*; D002417:Cattle; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000382:microbiology; D015536:Down-Regulation; D006801:Humans; D007778:Lactobacillus / Q000378:metabolism*; D008892:Milk / Q000382:microbiology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*
D000806:Angiotensin-Converting Enzyme Inhibitors; D002364:Caseins; D010455:Peptides; D007703:Peptidyl-Dipeptidase A