Facundo Heberty T F, Carreira Raquel S, de Paula Juliana G, Santos Célio C X, Ferranti Renato, Laurindo Francisco R M, Kowaltowski Alicia J
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes, 748, 05508-900, São Paulo, SP, Brazil.
Free Radic Biol Med. 2006 Feb 1;40(3):469-79. doi: 10.1016/j.freeradbiomed.2005.08.041. Epub 2005 Nov 9.
Mitochondrial ATP-sensitive K+ channels (mitoKATP) mediate ischemic preconditioning, a cardioprotective procedure. MitoKATP activity has been proposed to either enhance or prevent the release of reactive oxygen species. This study tested the redox effects of mitoKATP in order to clarify the role of these channels during preconditioning. We found no evidence that mitoKATP channels increase mitochondrial reactive oxygen species release directly. In addition, neither ischemic preconditioning nor the mitoKATP agonist diazoxide increased antioxidant defenses. Furthermore, increases in reactive oxygen species observed during ischemic preconditioning were not inhibited by mitoKATP antagonists, suggesting that they occur upstream of channel activity. Antioxidants were tested to verify if diazoxide-promoted ischemic protection was dependent on reactive oxygen species. N-Acetylcysteine proved to be an inadequate antioxidant for these tests since it directly interfered with the ability of diazoxide to activate mitoKATP. Catalase reversed the beneficial effect of preconditioning, but not of diazoxide, indicating that reactive oxygen species mediating preconditioning occur upstream of mitoKATP. Taken together, these results demonstrate that ischemic preconditioning increases reactive oxygen release independently of mitoKATP and suggest that the activity of this channel prevents oxidative reperfusion damage by decreasing reactive oxygen species production.
线粒体ATP敏感性钾通道（mitoKATP）介导缺血预处理，这是一种心脏保护过程。有人提出mitoKATP活性可增强或阻止活性氧的释放。本研究测试了mitoKATP的氧化还原作用，以阐明这些通道在预处理过程中的作用。我们没有发现mitoKATP通道直接增加线粒体活性氧释放的证据。此外，缺血预处理和mitoKATP激动剂二氮嗪均未增强抗氧化防御能力。此外，mitoKATP拮抗剂并未抑制缺血预处理期间观察到的活性氧增加，这表明活性氧增加发生在通道活性的上游。我们测试了抗氧化剂，以验证二氮嗪促进的缺血保护是否依赖于活性氧。N-乙酰半胱氨酸被证明不适用于这些测试，因为它直接干扰了二氮嗪激活mitoKATP的能力。过氧化氢酶逆转了预处理的有益作用，但未逆转二氮嗪的有益作用，这表明介导预处理的活性氧发生在mitoKATP的上游。综上所述，这些结果表明缺血预处理独立于mitoKATP增加活性氧释放，并表明该通道的活性通过减少活性氧的产生来防止氧化再灌注损伤。
