Venditti Paola, De Rosa Raffaella, Di Meo Sergio
Dipartimento di Fisiologia Generale ed Ambientale, Università di Napoli, Napoli, Italy.
Free Radic Biol Med. 2003 Sep 1;35(5):485-94. doi: 10.1016/s0891-5849(03)00331-9.
The effects of the thyroid state on oxidative damage, antioxidant capacity, susceptibility to in vitro oxidative stress and Ca(2+)-induced permeabilization of mitochondria from rat tissues (liver, heart, and gastrocnemious muscle) were examined. Hypothyroidism was induced by administering methimazole in drinking water for 15 d. Hyperthyroidism was elicited by a 10 d treatment of hypothyroid rats with triiodothyronine (10 micro g/100 g body weight). Mitochondrial levels of hydroperoxides and protein-bound carbonyls significantly decreased in hypothyroid tissues and were reported above euthroid values in hypothyroid rats after T(3) treatment. Mitochondrial vitamin E levels were not affected by changes of animal thyroid state. Mitochondrial Coenzyme Q9 levels decreased in liver and heart from hypothyroid rats and increased in all hyperthyroid tissues, while Coenzyme Q10 levels decreased in hypothyroid liver and increased in all hyperthyroid tissues. The antioxidant capacity of mitochondria was not significantly different in hypothyroid and euthyroid tissues, whereas it decreased in the hyperthyroid ones. Susceptibility to in vitro oxidative challenge decreased in mitochondria from hypothyroid tissues and increased in mitochondria from hyperthyroid tissues, while susceptibility to Ca(2+)-induced swelling decreased only in hypothyroid liver mitochondria and increased in mitochondria from all hyperthyroid tissues. The tissue-dependence of the mitochondrial susceptibility to stressful conditions in altered thyroid states can be explained by different thyroid hormone-induced changes in mitochondrial ROS production and relative amounts of mitochondrial hemoproteins and antioxidants. We suggest that susceptibilities to oxidants and Ca(2+)-induced swelling may have important implications for the thyroid hormone regulation of the turnover of proteins and whole mitochondria, respectively.
研究了甲状腺状态对大鼠组织（肝脏、心脏和腓肠肌）线粒体氧化损伤、抗氧化能力、体外氧化应激敏感性以及Ca(2+)诱导的线粒体通透性的影响。通过在饮水中给予甲巯咪唑15天诱导甲状腺功能减退。用三碘甲状腺原氨酸（10μg/100g体重）对甲状腺功能减退的大鼠进行10天治疗以诱发甲状腺功能亢进。甲状腺功能减退组织中线粒体过氧化氢和蛋白质结合羰基的水平显著降低，而在T(3)治疗后的甲状腺功能减退大鼠中，这些水平高于正常甲状腺值。线粒体维生素E水平不受动物甲状腺状态变化的影响。甲状腺功能减退大鼠肝脏和心脏中的线粒体辅酶Q9水平降低，而在所有甲状腺功能亢进组织中升高，而辅酶Q10水平在甲状腺功能减退肝脏中降低，在所有甲状腺功能亢进组织中升高。甲状腺功能减退和正常甲状腺组织中线粒体的抗氧化能力没有显著差异，而在甲状腺功能亢进组织中则降低。甲状腺功能减退组织中线粒体对体外氧化应激的敏感性降低，而甲状腺功能亢进组织中线粒体的敏感性增加，而对Ca(2+)诱导肿胀的敏感性仅在甲状腺功能减退的肝脏线粒体中降低，在所有甲状腺功能亢进组织的线粒体中增加。甲状腺状态改变时线粒体对压力条件敏感性的组织依赖性可以通过甲状腺激素诱导的线粒体ROS产生以及线粒体血红蛋白和抗氧化剂相对含量的不同变化来解释。我们认为，对氧化剂和Ca(2+)诱导肿胀的敏感性可能分别对甲状腺激素调节蛋白质周转和整个线粒体具有重要意义。
