Inhibition of growth of proline-requiring Chinese hamster ovary cells (CHO-k1) resulting from antagonism by a system amino acids.
CHO-K1 requires proline for growth. Two proline-independent revertants were isolated--K1-J and K1-6. CHO-K1 pro- is much more sensitive than the pro+ cell lines to inhibition of growth by addition to the medium of amino acids and amino acid analogues that are transported through the A system. In contrast, pro+ cells are as sensitive as, or in some cases slightly more sensitive than, pro- cells to glycine, basic amino acids, and to amino acids that are mainly transported by the L system. The A system analogue alpha(methylamino) isobutyric acid (MAIB) in low concentrations reacts competitively with proline to regulate the growth of pro- cells, yielding a Ki for MAIB of 0.56 mM. CHO-K1 and K1-6 transport proline at the same initial rate and are equally sensitive to the inhibition of proline transport by alanine. Alanine and MAIB inhibit proline transport strongly and similarly in CHO-K1. Thus although these compounds inhibit the transport of proline by both cell types to the same extent, pro+ cells are immune to the effect of this starvation since they are able to synthesize their own proline. We also describe a secondary inhibition caused by high A system amino acid concentrations that affects both pro- and pro+ cells.
D000596:Amino Acids / Q000378:metabolism* / Q000494:pharmacology; D000621:Aminoisobutyric Acids / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D001692:Biological Transport; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D010053:Ovary; D011392:Proline / Q000378:metabolism*
D000596:Amino Acids; D000621:Aminoisobutyric Acids; C017911:2-(methylamino)isobutyric acid; D011392:Proline