Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, 185 S Orange Ave., MSB G609, Newark, NJ 07103, USA.
J Cardiovasc Transl Res. 2010 Aug;3(4):314-20. doi: 10.1007/s12265-010-9184-8. Epub 2010 Mar 31.
Increases in oxidative stress in the heart play an important role in mediating hypertrophy, apoptosis, fibrosis, mitochondrial dysfunction, and the consequent development of heart failure. Although it has been widely believed that electron leakage from the mitochondrial electron transport chain is the primary source of oxidative stress in the failing heart, increasing lines of evidence suggest that enzymes which produce reactive oxygen species may also contribute to it. NADPH oxidases are transmembrane enzymes dedicated to producing superoxide (O(2)(-)) by transferring an electron from NAD(P)H to molecular oxygen. Nox4 is a major NADPH oxidase isoform expressed in the heart. Nox4 is localized primarily at mitochondria in cardiac myocytes, and upregulation of Nox4 hypertrophic stimuli enhances O(2)(-) production, apoptosis, and mitochondrial dysfunction, thereby playing an important role in mediating cardiac dysfunction. Since Nox4 could be a key molecule mediating oxidative stress and pathological hypertrophy, it may serve as an important target of heart failure treatment. In this review, the importance of NADPH oxidases as sources of increased oxidative stress in the failing heart and the role of Nox4 in mediating growth and death of cardiac myocytes are discussed.
心脏中氧化应激的增加在介导肥大、细胞凋亡、纤维化、线粒体功能障碍以及心力衰竭的发展中起着重要作用。尽管人们普遍认为，线粒体电子传递链的电子泄漏是心力衰竭中心脏氧化应激的主要来源，但越来越多的证据表明，产生活性氧物质的酶也可能对此有贡献。NADPH 氧化酶是一种跨膜酶，通过将电子从 NAD(P)H 转移到分子氧来专门产生超氧化物 (O2(-))。Nox4 是心脏中表达的主要 NADPH 氧化酶同工型。Nox4 主要位于心肌细胞的线粒体中，Nox4 对肥大刺激的上调增强了 O2(-)的产生、细胞凋亡和线粒体功能障碍，从而在介导心脏功能障碍中起着重要作用。由于 Nox4 可能是介导氧化应激和病理性肥大的关键分子，因此它可能成为心力衰竭治疗的重要靶点。本文综述了 NADPH 氧化酶作为心力衰竭中心脏氧化应激增加的来源的重要性以及 Nox4 在介导心肌细胞生长和死亡中的作用。
