Involvement of the system L amino acid transporter on uptake of S-nitroso-L-cysteine, an endogenous S-nitrosothiol, in PC12 cells.
Previously, we proposed that S-nitroso-L-cysteine, an endogenous S-nitrosothiol, was incorporated via the system L-like amino acid transporter(s) in rat brain slices. In this study, we investigated the effect of S-nitroso-L-cysteine on L-[3H]leucine uptake in PC12 cells (a neuronal cell line). L-[3H]Leucine uptake in PC12 cells was Na(+) independent and significantly inhibited by an inhibitor of system L and by L-phenylalanine, L-cysteine, L-methionine and L-leucine at 1 mM. The effects of L-alanine, L-serine and L-threonine were limited. S-Nitroso-L-cysteine, but not other nitric oxide compounds, inhibited L-[3H]leucine uptake, and this inhibitory effect was eliminated by washing with buffer. System L is composed of the 4F2 light chains (LAT1 or LAT2) and the heavy chain, and the transcripts of these components were detected in RNA from PC12 cells. These findings suggest that S-nitroso-L-cysteine is incorporated via the system L amino acid transporter and thus regulates cell responses in PC12 cells.
Nemoto
Takanori
T
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, 263-8522, Chiba, Japan.
Shimma
Naoko
N
Horie
Syunji
S
Saito
Takeshi
T
Okuma
Yasunobu
Y
Nomura
Yasuyuki
Y
Murayama
Toshihiko
T
D000409:Alanine / Q000737:chemistry / Q000494:pharmacology; D026905:Amino Acid Transport Systems / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000598:Amino Acids, Cyclic / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D003545:Cysteine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007930:Leucine / Q000493:pharmacokinetics; D020030:Nitric Oxide Donors / Q000494:pharmacology; D016716:PC12 Cells; D010649:Phenylalanine / Q000737:chemistry / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D026403:S-Nitrosothiols / Q000493:pharmacokinetics* / Q000494:pharmacology; D013237:Stereoisomerism; D014316:Tritium; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology
D026905:Amino Acid Transport Systems; D000598:Amino Acids, Cyclic; D020030:Nitric Oxide Donors; D012333:RNA, Messenger; D026403:S-Nitrosothiols; D014316:Tritium; D015091:beta-Alanine; C012924:2,2-dimethyl-beta-alanine; C006504:2-aminobicyclo(2,2,1)heptane-2-carboxylic acid; D010649:Phenylalanine; C021315:S-nitrosocysteine; D007930:Leucine; D003545:Cysteine; D000409:Alanine; D002118:Calcium