Inhibition of rat vascular smooth muscle cell proliferation by taurine and taurine analogues.
The growth of rat aorta vascular smooth muscle cells (VSMCs) was measured in the presence and absence of taurine. Concentrations of taurine as low as 0.3 mM in the culture medium inhibited the proliferation of the cells, as monitored by measuring cell count, and also inhibited the rate of DNA synthesis, as examined by measuring [3H]thymidine incorporation into DNA. However, even at the highest concentration of taurine (30 mM), the doubling time of the VSMCs was only increased by 38%. Protein content of the VSMCs was decreased by 30 mM taurine. [3H]Leucine incorporation into newly synthesized protein was not affected by the highest concentration of taurine tested (30 mM), indicating that taurine did not inhibit protein synthesis but rather decreased total protein content by inhibiting cellular proliferation. The effects of other amino acids such as alanine, glycine, and serine and of various taurine analogues such as beta-alanine, guanidinoethanesulfonic acid (GES), and isethionic acid also were tested at a concentration of 20 mM for their effects on the growth of the VSMCs. Alanine, glycine, and serine had only a minimal effect or no effect on cell count, quantity of protein, and incorporation of [3H]thymidine into DNA. GES, beta-alanine, and isethionic acid had a significant effect on cell count, protein content, and incorporation of [3H]thymidine into DNA. Beta-alanine was the only analogue tested that significantly depressed [3H]leucine incorporation into newly synthesized protein. It is concluded that taurine, GES, and isethionic acid inhibited proliferation of VSMCs but did not alter normal protein synthesis or survivability of VSMCs. In contrast, other amino acids, alanine, glycine and serine, had minimal effects on VSMC proliferation and protein synthesis, whereas beta-alanine appeared to be toxic, inhibiting both VSMC synthesis and de novo protein synthesis.
Zhang
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X
Department of Pharmacology, Texas Tech University Health Sciences Center, Lubbock 79430, USA.
Tenner
T E
TE
Lombardini
J B
JB
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004347:Drug Interactions; D005260:Female; D007930:Leucine / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D014176:Protein Biosynthesis; D011506:Proteins / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013654:Taurine / Q000031:analogs & derivatives / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D000596:Amino Acids; D011506:Proteins; D014316:Tritium; D013654:Taurine; D004247:DNA; D007930:Leucine; D013936:Thymidine