Hypoxic upregulation of arginase II in human lung endothelial cells
| Autor: | Karina Krotova, Edward R. Block, Jawaharlal M. Patel, Sergey Zharikov |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Small interfering RNA
medicine.medical_specialty Physiology Hypertension Pulmonary Cell Biology Nitric Oxide Cell Line Nitric oxide chemistry.chemical_compound Downregulation and upregulation Vascular Biology Internal medicine Basic Helix-Loop-Helix Transcription Factors medicine Humans Enzyme Inhibitors RNA Small Interfering Lung Cell Proliferation Arginase Cell growth Endothelial Cells Cell Biology Hypoxia (medical) Boronic Acids Cell Hypoxia Up-Regulation Endothelial stem cell medicine.anatomical_structure Endocrinology chemistry Microvessels Cancer research Hypoxia-Inducible Factor 1 medicine.symptom |
| Zdroj: | American Journal of Physiology-Cell Physiology. 299:C1541-C1548 |
| ISSN: | 1522-1563 0363-6143 |
| Popis: | Activated arginase has been implicated in many diseases including cancer, immune cell dysfunction, infections, and vascular disease. Enhanced arginase activity has been reported in lungs of patients with pulmonary artery hypertension. We used hypoxia as a model for pulmonary hypertension and studied the effect of exposure to hypoxia on arginase activity in human lung microvascular endothelial cells (HMVEC). Hypoxia induces upregulation of arginase activity as well as mRNA and protein levels of arginase II (Arg II), the only arginase isoform we were able to identify in HMVEC. In endothelial cells, arginase shares and competes for the substrate l-arginine with nitric oxide (NO) synthase (NOS). Through regulation of substrate availability for NOS, arginase is able to modulate NO production. To evaluate the role of Arg II in regulation of NO production under hypoxia, we compared NO output (RFL-6 reporter assay) in cells with normal and silenced Arg II. Exposure to hypoxia led to an increase in NO levels produced by HMVEC. Inhibition of Arg II by specific small interfering RNA or by the pharmacological inhibitor BEC additionally enhanced the levels of NO. Another possible role for activated arginase is involvement in regulation of cell proliferation. However, we showed that hypoxia decreased cell proliferation and upregulated Arg II did not have an effect on cell proliferation. Since hypoxia-inducible factors (HIF) are a family of transcriptional factors activated by hypoxia, we tested the possibility of involvement of HIF-1 and HIF-2 in regulation of Arg II under hypoxia. The silencing of HIF-2 but not HIF-1 prevented the activation of Arg II by hypoxia. |
| Databáze: | OpenAIRE |
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