Elevated Transglutaminase 2 Activity Is Associated with Hypoxia-Induced Experimental Pulmonary Hypertension in Mice
| Autor: | Rod R. Warburton, Cornelius Klöck, Zachary Herrera, Deniz Toksoz, Chaitan Khosla, Thomas R. DiRaimondo, Nicholas S. Hill, Barry L. Fanburg, Krishna Penumatsa |
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| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Tissue transglutaminase Hypertension Pulmonary Biology Biochemistry Article Muscle hypertrophy Mice GTP-Binding Proteins In vivo Internal medicine medicine Animals Humans Protein Glutamine gamma Glutamyltransferase 2 Enzyme Inhibitors Hypoxia Lung Transglutaminases General Medicine Hypoxia (medical) medicine.disease Pulmonary hypertension Enzyme Activation Mice Inbred C57BL medicine.anatomical_structure Endocrinology Ventricle Positron-Emission Tomography Ventricular pressure biology.protein Molecular Medicine medicine.symptom |
| Zdroj: | ACS Chemical Biology. 9:266-275 |
| ISSN: | 1554-8937 1554-8929 |
| Popis: | Previous studies in human patients and animal models have suggested that transglutaminase 2 (TG2) is upregulated in pulmonary hypertension (PH), a phenomenon that appears to be associated with the effects of serotonin (5-hydroxytryptamine; 5-HT) in this disease. Using chemical tools to interrogate and inhibit TG2 activity in vivo, we have shown that pulmonary TG2 undergoes marked post-translational activation in a mouse model of hypoxia-induced PH. We have also identified irreversible fluorinated TG2 inhibitors that may find use as non-invasive positron emission tomography probes for diagnosis and management of this debilitating, lifelong disorder. Pharmacological inhibition of TG2 attenuated the elevated right ventricular pressure but had no effect on hypertrophy of the right ventricle of the heart. A longitudinal study of pulmonary TG2 activity in PH patients is warranted. |
| Databáze: | OpenAIRE |
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