Transport of Antihypertensive Peptide RVPSL, Ovotransferrin 328-332, in Human Intestinal Caco-2 Cell Monolayers.
The objective of this study was to investigate the transepithelial transport of RVPSL (Arg-Val-Pro-Ser-Leu), an egg-white-derived peptide with angiotensin I-converting enzyme (ACE) inhibitory and antihypertensive activity, in human intestinal Caco-2 cell monolayers. Results revealed that RVPSL could be passively transported across Caco-2 cell monolayers. However, during the process of transport, 36.31% ± 1.22% of the initial RVPSL added to the apical side was degraded, but this degradation decreased to 23.49% ± 0.68% when the Caco-2 cell monolayers were preincubated with diprotin A (P < 0.001), suggesting that RVPSL had a low resistance to various brush border membrane peptidases. When transport from the apical side to the basolateral side was investigated, the apparent permeability coefficient (Papp) was (6.97 ± 1.11) × 10(-6) cm/s. The transport route of RVPSL appears to be the paracellular pathway via tight junctions, as only cytochalasin D, a disruptor of tight junctions (TJs), significantly increased the transport rate (P < 0.001). In addition, the relationship between the structure of RVPSL and transport across Caco-2 cell monolayers was studied by mutation of RVPSL. It was found that N-terminal Pro residues were more beneficial for transport of pentapeptides across Caco-2 cell monolayers than Arg and Val. Furthermore, RVPSL could be more easily transported as smaller peptides, especially in the form of dipeptides and tripeptides.
Laboratory of Nutrition and Functional Food, Jilin University , Changchun 130062, People's Republic of China.
Long
L
Ding
Laboratory of Nutrition and Functional Food, Jilin University , Changchun 130062, People's Republic of China.
Liying
L
Wang
Laboratory of Nutrition and Functional Food, Jilin University , Changchun 130062, People's Republic of China.
Yan
Y
Zhang
Laboratory of Nutrition and Functional Food, Jilin University , Changchun 130062, People's Republic of China.
Jingbo
J
Liu
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001692:Biological Transport; D018938:Caco-2 Cells; D002851:Chromatography, High Pressure Liquid; D004527:Egg Proteins / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008871:Microvilli / Q000201:enzymology; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D010447:Peptide Hydrolases / Q000378:metabolism; D013329:Structure-Activity Relationship
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004527:Egg Proteins; D010446:Peptide Fragments; C000589715:arginyl-valyl-prolyl-seryl-leucine; D010447:Peptide Hydrolases
Caco-2 cell monolayer; antihypertensive peptide; brush border membrane peptidase; egg white; transport