Nox4-derived reactive oxygen species mediate cardiomyocyte injury in early type 1 diabetes
Nox4-derived reactive oxygen species mediate cardiomyocyte injury in early type 1 diabetes
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DOI：
10.1152/ajpcell.00331.2011
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发表时间：
2012-02-01
影响因子：
5.5
通讯作者：
Abboud, Hanna E.
中科院分区：
文献类型：
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作者：
Maalouf, Rita M.;Eid, Assaad A.;Abboud, Hanna E.
Maalouf RM，Eid AA，Gorin YC，Block K，Escobar GP，Bailey S，Abboud HE. nox 4源性活性氧介导1型糖尿病早期心肌细胞损伤。美国生理学杂志细胞生理学302：C597-C604，2012年。首次发表于2011年10月26日; doi：10.1152/ajpcell.00331.2011。氧化应激导致糖尿病性心肌病。本研究探讨了NADPH氧化酶Nox 4作为活性氧（ROS）来源在糖尿病心肌病发生发展中的作用。硫代磷酸化的反义（AS）或正义（S）寡核苷酸的Nox 4的给药2周的糖尿病大鼠链脲佐菌素。糖尿病大鼠左心室组织中NADPH氧化酶活性、ROS生成和Nox 4表达增加，但Nox 1或Nox 2表达增加。肥大和肌纤维化的分子标志物，包括纤连蛋白、胶原、α-平滑肌肌动蛋白和β-肌球蛋白重链的表达也增加。这些参数被衰减的AS，但不S Nox 4的管理。此外，在糖尿病大鼠中观察到的收缩性损害在AS-但不是S-治疗的动物中得到预防。将培养的心肌细胞暴露于25 mM葡萄糖[高葡萄糖（HG）]增加NADPH氧化酶活性，Nox 4表达和心脏损伤的分子标志物。HG的这些作用在用含有显性负性形式的Nox 4的腺病毒载体感染的细胞中被阻止。这项研究提供了强有力的证据，证明Nox 4是左心室活性氧的重要来源，并且Nox 4衍生的活性氧有助于1型糖尿病早期阶段的心肌病。
Maalouf RM, Eid AA, Gorin YC, Block K, Escobar GP, Bailey S, Abboud HE. Nox4-derived reactive oxygen species mediate cardiomyocyte injury in early type 1 diabetes. Am J Physiol Cell Physiol 302: C597-C604, 2012. First published October 26, 2011; doi: 10.1152/ajpcell.00331.2011.-Oxidative stress contributes to diabetic cardiomyopathy. This study explored the role of the NADPH oxidase Nox4 as a source of reactive oxygen species (ROS) involved in the development of diabetic cardiomyopathy. Phosphorothioated antisense (AS) or sense (S) oligonucleotides for Nox4 were administered for 2 wk to rats made diabetic by streptozotocin. NADPH oxidase activity, ROS generation, and the expression of Nox4, but Nox1 or Nox2, were increased in left ventricular tissue of the diabetic rats. Expression of molecular markers of hypertrophy and myofibrosis including fibronectin, collagen, alpha-smooth muscle actin, and beta-myosin heavy chain were also increased. These parameters were attenuated by the administration of AS but not S Nox4. Moreover, the impairment of contractility observed in diabetic rats was prevented in AS- but not S-treated animals. Exposure of cultured cardiac myocytes to 25 mM glucose [high glucose (HG)] increased NADPH oxidase activity, the expression of Nox4, and molecular markers of cardiac injury. These effects of HG were prevented in cells infected with adenoviral vector containing a dominant negative form of Nox4. This study provides strong evidence that Nox4 is an important source of ROS in the left ventricle and that Nox4-derived ROS contribute to cardiomyopathy at early stages of type 1 diabetes.