Silvestri E, Moreno M, Lombardi A, Ragni M, de Lange P, Alexson S E H, Lanni A, Goglia F
Dipartimento di Scienze Biologiche ed Ambientali, Università degli Studi del Sannio, Via Port'Arsa 11, 82100 Benevento, Italy.
FEBS Lett. 2005 Mar 14;579(7):1639-45. doi: 10.1016/j.febslet.2005.02.022.
In vitro, uncoupling protein 3 (UCP3)-mediated uncoupling requires cofactors [e.g., superoxides, coenzyme Q (CoQ) and fatty acids (FA)] or their derivatives, but it is not yet clear whether or how such activators interact with each other under given physiological or pathophysiological conditions. Since triiodothyronine (T3) stimulates lipid metabolism, UCP3 expression and mitochondrial uncoupling, we examined its effects on some biochemical pathways that may underlie UCP3-mediated uncoupling. T3-treated rats (Hyper) showed increased mitochondrial lipid-oxidation rates, increased expression and activity of enzymes involved in lipid handling and increased mitochondrial superoxide production and CoQ levels. Despite the higher mitochondrial superoxide production in Hyper, euthyroid and hyperthyroid mitochondria showed no differences in proton-conductance when FA were chelated by bovine serum albumin. However, mitochondria from Hyper showed a palmitoyl-carnitine-induced and GDP-inhibited increased proton-conductance in the presence of carboxyatractylate. We suggest that T3 stimulates the UCP3 activity in vivo by affecting the complex network of biochemical pathways underlying the UCP3 activation.
在体外，解偶联蛋白3（UCP3）介导的解偶联需要辅因子[如超氧化物、辅酶Q（CoQ）和脂肪酸（FA）]或其衍生物，但在特定的生理或病理生理条件下，这些激活剂是否以及如何相互作用尚不清楚。由于三碘甲状腺原氨酸（T3）可刺激脂质代谢、UCP3表达和线粒体解偶联，我们研究了其对一些可能是UCP3介导解偶联基础的生化途径的影响。经T3处理的大鼠（Hyper）表现出线粒体脂质氧化速率增加、参与脂质处理的酶的表达和活性增加、线粒体超氧化物生成增加以及CoQ水平升高。尽管Hyper组的线粒体超氧化物生成较高，但当脂肪酸被牛血清白蛋白螯合时，正常甲状腺和甲状腺功能亢进的线粒体在质子传导方面没有差异。然而，在存在羧基苍术苷的情况下，Hyper组的线粒体在棕榈酰肉碱诱导且GDP抑制的情况下质子传导增加。我们认为，T3通过影响UCP3激活所涉及的复杂生化途径网络来刺激体内的UCP3活性。
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