Elevated transglutaminase 2 activity is associated with hypoxia-induced experimental pulmonary hypertension in mice.
Elevated transglutaminase 2 activity is associated with hypoxia-induced experimental pulmonary hypertension in mice.
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DOI：
10.1021/cb4006408
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发表时间：
2014-01-17
影响因子：
4
通讯作者：
Fanburg, Barry
中科院分区：
文献类型：
--
作者：
DiRaimondo, Thomas R.;Kloeck, Cornelius;Warburton, Rod;Herrera, Zachary;Penumatsa, Krishna;Toksoz, Deniz;Hill, Nicholas;Khosla, Chaitan;Fanburg, Barry
先前对人类患者和动物模型的研究表明，转谷氨酰胺酶 2 (TG2) 在肺动脉高压 (PH) 中上调，这种现象似乎与血清素（5-羟色胺；5-HT）在这种疾病中的作用有关。使用化学工具来检测和抑制体内 TG2 活性，我们发现肺 TG2 在缺氧诱导的 PH 小鼠模型中经历了明显的翻译后激活。我们还发现了不可逆的氟化 TG2 抑制剂，可用作非侵入性正电子发射断层扫描探针，用于诊断和治疗这种使人衰弱的终生疾病。 TG2 的药理抑制可减弱右心室压力升高，但对心脏右心室肥大没有影响。有必要对 PH 患者的肺 TG2 活性进行纵向研究。
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.
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