Elevated Transglutaminase 2 Activity Is Associated with Hypoxia-Induced Experimental Pulmonary Hypertension in Mice

详细信息    查看全文

• 作者：Thomas R. DiRaimondo ; Cornelius Kl?ck ; Rod Warburton ; Zachary Herrera ; Krishna Penumatsa ; Deniz Toksoz ; Nicholas Hill ; Chaitan Khosla ; Barry Fanburg
• 刊名：ACS Chemical Biology
• 出版年：2014
• 出版时间：January 17, 2014
• 年：2014
• 卷：9
• 期：1
• 页码：266-275
• 全文大小：541K
• ISSN：1554-8937

文摘

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.