Premium
Stimulated Lymphocytes from Patients with ARG1 Single Nucleotide Polymorphism rs2781666 have Augmented NO Production in Hyperoxia
Author(s) -
Trittmann Jennifer,
Jin Yi,
Chen Bernadette,
Nelin Leif
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.662.6
Subject(s) - arginase , single nucleotide polymorphism , hyperoxia , snp , endogeny , nitric oxide , endocrinology , arginine , biology , medicine , apoptosis , chemistry , microbiology and biotechnology , biochemistry , genotype , gene , amino acid , lung
L‐arginine metabolism by arginase and NO synthase have opposing effects on vascular tone and remodeling, with arginase activity favoring vasoconstriction and vascular remodeling. Our group recently found that the arginase I ( ARG1) single nucleotide polymorphism (SNP) rs2781666 is associated with a decreased risk of PH in infants with BPD. We hypothesized that the mechanism for protection against PH in BPD is due to lower levels of arginase I and thereby greater endogenous NO production. Lymphocytes from BPD patients were genotyped for the ARG1 SNP rs2781666 (GG‐wildtype, TT minor allele), stimulated with IL‐4, IL‐13, and phorbol myristate acetate (PMA), and exposed to either normoxia (21%O 2 ) or hyperoxia (90%O 2 ) for 24 hours. Cell lysates from lymphocytes were assayed for arginase I, arginase II, and cleaved caspase‐3 protein by western blot. The media was assayed for nitrites. Stimulated lymphocytes from patients homozygous for the ARG1 rs2781666 SNP exposed to hyperoxia have decreased levels of arginase I protein, no difference in arginase II protein, increased nitrite levels, and increased cleaved caspase‐3 protein, as compared to lymphocytes from patients homozygous for the wild‐type allele. These data are consistent with our hypothesis that BPD patients who have the ARG1 rs2781666 SNP are protected against PH during hyperoxic exposure by producing lower levels of arginase I and greater levels of endogenous NO. The increase in endogenous NO in these lymphocytes was associated with increased apoptosis as demonstrated by greater cleaved caspase‐3 activation.