Adenosine induces endothelial apoptosis by activating protein tyrosine phosphatase: A possible role of p38α
Autor: | Julie Newton, Nancy Parks, Anthony Smeglin, Sharon Rounds, Elizabeth O. Harrington |
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Předmět: |
Pulmonary and Respiratory Medicine
medicine.medical_specialty Programmed cell death Adenosine Homocysteine Physiology Angiogenesis Apoptosis Protein tyrosine phosphatase Biology Pulmonary Artery p38 Mitogen-Activated Protein Kinases Cell Line chemistry.chemical_compound Cytosol Mitogen-Activated Protein Kinase 11 Physiology (medical) Internal medicine medicine Animals Enzyme Inhibitors Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Cell Membrane JNK Mitogen-Activated Protein Kinases Cell Biology Genistein Endothelial stem cell Kinetics Endocrinology chemistry Cancer research Cattle Endothelium Vascular Signal transduction Mitogen-Activated Protein Kinases Protein Tyrosine Phosphatases medicine.drug |
Zdroj: | Scopus-Elsevier |
Popis: | Endothelial cell (EC) apoptosis is important in vascular injury, repair, and angiogenesis. Homocysteine and/or adenosine exposure of ECs causes apoptosis. Elevated homocysteine or adenosine occurs in disease states such as homocysteinuria and tissue necrosis, respectively. We examined the intracellular signaling mechanisms involved in this pathway of EC apoptosis. Inhibition of protein tyrosine phosphatase (PTPase) attenuated homocysteine- and/or adenosine-induced apoptosis and completely blocked apoptosis induced by the inhibition of S-adenosylhomocysteine hydrolase with MDL-28842. Consistent with this finding, the tyrosine kinase inhibitor genistein enhanced apoptosis in adenosine-treated ECs. Adenosine significantly elevated the PTPase activity in the ECs. Mitogen-activated protein kinase activities were examined to identify possible downstream targets for the upregulated PTPase(s). Extracellular signal-regulated kinase (ERK) 1 activity was slightly elevated in adenosine-treated ECs, whereas ERK2, c-Jun NH2-terminal kinase-1, or p38β activities differed little. The mitogen-activated protein kinase-1 inhibitor PD-98059 enhanced DNA fragmentation, suggesting that increased ERK1 activity is a result but not a cause of apoptosis in adenosine-treated ECs. Adenosine-treated ECs had diminished p38α activity compared with control cells; this effect was blunted on PTPase inhibition. These results indicate that PTPase(s) plays an integral role in the induction of EC apoptosis upon exposure to homocysteine and/or adenosine, possibly by the attenuation of p38α activity. |
Databáze: | OpenAIRE |
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