Park S H, Paulsen S R, Gammon S R, Mustard K J, Hardie D G, Winder W W
Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah 84602, USA.
J Appl Physiol (1985). 2002 Dec;93(6):2081-8. doi: 10.1152/japplphysiol.00504.2002.
AMP-activated protein kinase (AMPK) consists of three subunits: alpha, beta, and gamma. Two isoforms exist for the alpha-subunit (alpha(1) and alpha(2)), two for the beta-subunit (beta(1) and beta(2)), and three for the gamma-subunit (gamma(1), gamma(2), and gamma(3)). Although the specific roles of the beta- and gamma-subunits are not well understood, the alpha-subunit isoforms contain the catalytic site and also the phosphorylation/activation site for the upstream kinase. This study was designed to determine the role of thyroid hormones in controlling expression levels of these AMPK subunits and of one downstream target, acetyl-CoA carboxylase (ACC), in muscle. AMPK subunit and ACC levels were determined by Western blots in control rats, in rats given 0.01% propylthiouracil (PTU) in drinking water for 3 wk, and in rats given 3 mg of thyroxine and 1 mg of triiodothyronine per kilogram chow for 1 or 3 wk. In gastrocnemius muscle, all isoforms of AMPK subunits were significantly increased in rats given thyroid hormones for 3 wk vs. those treated with PTU. Similar patterns were seen in individual muscle types. Expression of muscle ACC was also significantly increased in response to 3 wk of treatment with excess thyroid hormones. Muscle content of malonyl-CoA was elevated in PTU-treated rats and depressed in thyroid hormone-treated rats. These data provide evidence that skeletal muscle AMPK subunit and ACC expression is partially under the control of thyroid hormones.
AMP激活的蛋白激酶（AMPK）由三个亚基组成：α、β和γ。α亚基有两种同工型（α(1)和α(2)），β亚基有两种（β(1)和β(2)），γ亚基有三种（γ(1)、γ(2)和γ(3)）。尽管β和γ亚基的具体作用尚未完全明确，但α亚基同工型包含催化位点以及上游激酶的磷酸化/激活位点。本研究旨在确定甲状腺激素在控制肌肉中这些AMPK亚基以及一个下游靶点乙酰辅酶A羧化酶（ACC）表达水平方面的作用。通过蛋白质免疫印迹法测定了对照大鼠、饮用含0.01%丙硫氧嘧啶（PTU）的水3周的大鼠以及每千克饲料给予3毫克甲状腺素和1毫克三碘甲状腺原氨酸1周或3周的大鼠中AMPK亚基和ACC的水平。在腓肠肌中，给予甲状腺激素3周的大鼠与给予PTU的大鼠相比，AMPK亚基的所有同工型均显著增加。在各个肌肉类型中也观察到类似的模式。给予过量甲状腺激素治疗3周后，肌肉ACC的表达也显著增加。在PTU处理的大鼠中，丙二酰辅酶A的肌肉含量升高，而在甲状腺激素处理的大鼠中则降低。这些数据提供了证据，表明骨骼肌AMPK亚基和ACC的表达部分受甲状腺激素的控制。
