Synthetic peptide (P-21) derived from Asp-hemolysin inhibits the induction of apoptosis on HUVECs by lysophosphatidylcholine.
Lysophosphatidylcholine (LPC), formed during low-density lipoprotein (LDL) oxidation and located within atherosclerotic plaques, regulates a variety of cellular functions, some of which could be construed to promote atherosclerotic lesion development, including vascular muscle cell proliferation, monocyte attraction, and endothelial cell apoptosis. We have previously reported that the synthetic peptide derived from Asp-hemolysin, named P-21, inhibits oxidized LDL (OxLDL)-induced macrophage proliferation through binding of P-21 to OxLDL. In this study, to clarify the interaction between P-21 and LPC as a typical lipid moiety of OxLDL, we examined the influence of P-21 on LPC-induced apoptosis in human umbilical vein endothelial cells (HUVECs). Based on flow cytometric analysis, using annexin V-fluorescein isothiocyanate and propidium iodide as probes to assess apoptosis, LPC induced the apoptosis of HUVECs, and P-21 significantly inhibited this activity by 82.4%. Furthermore, dissociation-enhanced lanthanide fluorometric immunoassay indicated that LPC inhibited the binding of P-21 to OxLDL in a dose-dependent manner. A 50% inhibition dose was estimated to be 4.65 microM of LPC. These results suggest that P-21 inhibits LPC-induced HUVEC apoptosis through binding of P-21 to LPC.
Tsutsumi
Hiromu
H
First Department of Hygienic Chemistry, Tohoku Pharmaceutical University, Sendai, Miyagi, Japan.
Kumagai
Takeshi
T
Naitoo
Saori
S
Ebina
Keiichi
K
Yokota
Katsushi
K
D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D008077:Lipoproteins, LDL / Q000737:chemistry; D008244:Lysophosphatidylcholines / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology*; D010084:Oxidation-Reduction; D011485:Protein Binding
D017304:Annexin A5; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines