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Hypoxia upregulates arginase 2 in human endothelial cells
Author(s) -
Krotova Karina,
Zharikov Sergey,
Patel Jawaharlal M,
Block Edward R
Publication year - 2009
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.23.1_supplement.1024.7
Subject(s) - arginase , hypoxia (environmental) , nitric oxide , downregulation and upregulation , nitric oxide synthase , chemistry , microbiology and biotechnology , arginine , biology , endocrinology , biochemistry , oxygen , gene , organic chemistry , amino acid
We studied the effects of hypoxia on arginase expression and activity in human endothelial cells (EC). We found that in human lung microvascular EC and human pulmonary artery EC only one isoform‐ arginase 2 (Arg2) ‐is expressed and hypoxia upregulates the activity as well as mRNA and protein levels of Arg 2. In EC arginase shares and competes for the substrate L‐arginine with nitric oxide synthase (NOS). Through regulation of substrate availability for NOS arginase is able to modulate nitric oxide (NO) production. To evaluate the role of Arg 2 in regulation of NO production under hypoxia we compared NO output (RFL‐6 reporter assay) in cells with normal and silenced Arg 2. Cells treated with the arginase inhibitor BEC or with an Arg 2 siRNA produced more available NO both in normoxia and especially in hypoxia. We sought to determine the signaling pathways involved in the upregulation of Arg 2. Since HIF is a family of transcriptional factors activated by hypoxia, we tested the possibility of involvement of HIF‐1 and HIF‐2 in regulation of Arg 2 under hypoxia. The silencing of HIF‐2 but not HIF‐1 prevented the activation of Arg 2 by hypoxia. This work was supported by Florida DOH (KK), VA and NIH (JMP).