Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cellular glutathione peroxidase (GPx-1), a selenocysteine-containing enzyme, plays a central role in protecting cells from oxidative injury. GPx-1 is ubiquitously expressed in eukaryotic cells where it reduces hydrogen and lipid peroxides to alcohols. Adenosine, which is released from stressed or injured cells, protects against ischemia/reperfusion injury and apoptosis. In this study, we hypothesize that the cytoprotective effect of adenosine involves an increase in the activity of GPx-1. Treatment of human primary pulmonary artery endothelial cells (HPAECs) with 50 micromol/L adenosine in the presence of 10 micromol/L erytho-9-(2-hydroxy-3-nonyl)adenine (EHNA), an adenosine deaminase inhibitor, for 48 hours increased GPx-1 mRNA levels 2-fold. GPx-1 protein and enzyme activity also increased approximately 2-fold after treatment. The induction of GPx-1 expression was found to be a consequence of increased mRNA stability and not an increase in transcription. Bisindolylmaleimide I (BIM), a protein kinase C signaling pathway inhibitor, significantly attenuated the induction of GPx-1 mRNA by approximately 36%. The adenosine/EHNA-treated cells were more resistant to hydrogen peroxide stress. Both pharmacological inhibition and siRNA knockdown of GPx-1 attenuated the protective affect of adenosine/EHNA treatment, indicating that the adenosine-induced increase in GPx-1 contributes to an increase in cellular protection against oxidative stress. These data suggest that adenosine may protect the cardiovascular system from ischemia/reperfusion injury, in part, by enhancing the expression of the central intracellular antioxidant enzyme, GPx-1.
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PMID:Adenosine-dependent induction of glutathione peroxidase 1 in human primary endothelial cells and protection against oxidative stress. 1580 13