L-phenylalanine and smooth muscle cell proliferation from SHR and WKY rats.
Cell growth and proliferation were evaluated in cultured vascular smooth muscle cells (VSMCs) isolated from spontaneously hypertensive rat (SHR) and normotensive Wistar-Kyoto (WKY) rat aortae by measuring [3H]-thymidine incorporation into newly synthesized DNA and by determining cell number, respectively. The results showed that in cultures from both rat strains (1) serum-, basic fibroblast growth factor (bFGF)- and thrombin-induced DNA synthesis were inhibited by L-phenylalanine dose-dependently; (2) L-phenylalanine inhibited cell proliferation in response to serum in a concentration-dependent manner; (3) L-phenylalanine inhibited serum-induced proto-oncogene c-fos and c-myc expression; (4) L-tyrosine, L-histidine and D-phenylalanine failed to mimic the inhibitory effect of L-phenylalanine. All these data demonstrate that L-phenylalanine could exert a direct and specific antiproliferative effect on VSMCs suggesting that such effect can account for the antihypertensive action of this amino acid observed in SHR.
Gao
P J
PJ
Affiliated Ruijin Hospital and Shanghai Institute of Hypertension, Shanghai Second Medical University, Shanghai 200025, China.
Zhu
D L
DL
Zhan
Y M
YM
Stepien
O
O
Marche
P
P
Zhao
G S
GS
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D010649:Phenylalanine / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D016222:Fibroblast Growth Factor 2; D010649:Phenylalanine; D004247:DNA