Dipartimento delle Scienze Biologiche, Sezione di Fisiologia, Università di Napoli, I-80134 Napoli, Italy.
Mol Cell Endocrinol. 2011 Jul 20;341(1-2):55-62. doi: 10.1016/j.mce.2011.05.013. Epub 2011 Jun 1.
Thyronamines T(0)AM and T(1)AM are naturally occurring decarboxylated thyroid hormone derivatives. Their in vivo administration induces effects opposite to those induced by thyroid hormone, including lowering of body temperature. Since the mitochondrial energy-transduction apparatus is known to be a potential target of thyroid hormone and its derivatives, we investigated the in vitro effects of T(0)AM and T(1)AM on the rates of O(2) consumption and H(2)O(2) release by rat liver mitochondria. Hypothyroid animals were used because of the low levels of endogenous thyronamines. We found that both compounds are able to reduce mitochondrial O(2) consumption and increase H(2)O(2) release. The observed changes could be explained by a partial block, operated by thyronamines, at a site located near the site of action of antimycin A. This hypothesis was confirmed by the observation that thyronamines reduced the activity of Complex III where the site of antimycin action is located. Because thyronamines exerted their effects at concentrations comparable to those found in hepatic tissue, it is conceivable that they can affect in vivo mitochondrial O(2) consumption and H(2)O(2) production acting as modulators of thyroid hormone action.
甲状腺素胺 T(0)AM 和 T(1)AM 是天然存在的脱羧甲状腺激素衍生物。它们在体内的给药会引起与甲状腺激素相反的作用,包括降低体温。由于线粒体能量转换装置被认为是甲状腺激素及其衍生物的潜在靶标,我们研究了 T(0)AM 和 T(1)AM 对大鼠肝线粒体 O(2)消耗和 H(2)O(2)释放速率的体外影响。使用甲状腺功能减退动物是因为内源性甲状腺素胺水平较低。我们发现这两种化合物都能够降低线粒体 O(2)消耗并增加 H(2)O(2)释放。观察到的变化可以通过甲状腺素胺在靠近抗霉素 A 作用部位的部位进行部分阻断来解释。这一假设得到了证实,因为甲状腺素胺降低了位于抗霉素作用部位的复合物 III 的活性。由于甲状腺素胺在与肝组织中发现的浓度相当的浓度下发挥作用,可以想象它们可以通过作为甲状腺激素作用的调节剂来影响体内线粒体 O(2)消耗和 H(2)O(2)的产生。