Characteristics and regulation of proline transport in cultured glioblastoma cells.
L-Proline transport in C6 glioblastoma cells takes place mainly via a saturable Na(+)-dependent mechanism. The uptake process can be discriminated into two components, system A and system ASC. A minor proportion of L-proline transport is carried out by the ASC system, which appears to be constitutively expressed by the cell, but most is by system A which shows adaptive responses to amino acid deprivation and sensitivity to N-methyl-alpha-aminoisobutyric acid. The transport system is inhibited by proline derivatives, such as methyl and benzyl esters, and also hydroxyproline, and is stereospecific. Incubation of glioblastoma cells with phorbol 12-myristate 13-acetate led to concentration- and time-dependent decreases in L-proline transport. This effect could be mimicked by exogenous phospholipase C. Proline transport is significantly stimulated in the presence of Ca(2+)-mobilization agents and strongly inhibited in the absence of Ca2+. The present data suggest a complex regulation of L-proline transport by different kinases in glioblastoma cells.
Zafra
F
F
Centro de Biología Molecular Severo Ochoa, Facultad de Ciencias, Universidad Autónoma de Madrid, Spain.
Aragón
C
C
Giménez
C
C
D000621:Aminoisobutyric Acids / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D007700:Kinetics; D011392:Proline / Q000378:metabolism*; D051381:Rats; D012964:Sodium / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000494:pharmacology
D000621:Aminoisobutyric Acids; C017911:2-(methylamino)isobutyric acid; D011392:Proline; D012964:Sodium; D010738:Type C Phospholipases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium