Journal
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
Volume 292, Issue 4, Pages C1263-C1271Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00382.2006
Keywords
nitric oxide; nitrosothiols; system L transporter; endothelial cells; smooth muscle cells; red blood cells
Categories
Ask authors/readers for more resources
System L amino acid transporters have been shown to be responsible for cellular uptake of S- nitroso- L- cysteine ( L- CSNO). In this study, we examined the characteristics of L- CSNO uptake in Xenopus laevis oocytes expressing system L transporters and found that uptake increased only when both 4F2 heavy chain ( 4F2HC) and either L- type amino acid transporter 1 ( LAT1) or LAT2 light chain were coexpressed. The Km for transport was 57 +/- 8 mu M for 4F2HC- LAT1 and 520 +/- 52 mu M for 4F2HC- LAT2. Vascular endothelial and smooth muscle cells were shown to express transcripts for 4F2HC and for both LAT1 and LAT2. Transport of L- CSNO into red blood cells, endothelial cells, and smooth muscle cells was inhibited by 2- aminobicyclo( 2.2.1) heptane- 2- carboxylic acid ( BCH) and by large neutral amino acids demonstrating functional system L transporters in each cell type. Uptake of L- CSNO led to accumulation of cellular S- nitrosothiols and inhibition of both growth factor-induced ERK phosphorylation and TNF-alpha- mediated I kappa B degradation. Similar effects were seen when cells were incubated simultaneously with S- nitrosoalbumin and L- cysteine but not with D- cysteine or with S- nitrosoalbumin alone. In each case, nitrosylation of proteins and cellular responses were blocked by BCH. Together, these data suggest that transmembrane movement of nitric oxide ( NO) equivalents from the plasma albumin NO reservoir is mediated by cysteine, which serves as a carrier. The mechanism requires transnitrosylation from S- nitrosoalbumin to free cysteine and activity of system L transporters, thereby providing a unique pathway for cellular responses to S- nitrosoalbumin.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available