Attenuated cardiovascular hypertrophy and oxidant generation in response to angiotensin II infusion in glutaredoxin-1 knockout mice.
Attenuated cardiovascular hypertrophy and oxidant generation in response to angiotensin II infusion in glutaredoxin-1 knockout mice.
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DOI：
10.1016/j.freeradbiomed.2010.07.005
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发表时间：
2010-10-15
影响因子：
7.4
通讯作者：
Matsui, Reiko
中科院分区：
文献类型：
--
作者：
Bachschmid, Markus M.;Xu, Shanqin;Maitland-Toolan, Karlene A.;Ho, Ye-Shih;Cohen, Richard A.;Matsui, Reiko
关键词：
谷氧还蛋白-1(Glutaredosin-1，GLRX)是一种硫醇转移酶，调节蛋白质S-谷胱甘肽的氧化还原。为了阐明内源性Glrx在心血管疾病中的作用，给Glrx基因敲除(KO)小鼠注入血管紧张素II(Ang II)6天。经Ang II输注后，WT和Glrx KO小鼠的体重和血压相似。然而，与WT小鼠相比，Glrx KO小鼠表现出(1)较少的心脏和主动脉中层肥厚，(2)二氢乙锭染色和硝基酪氨酸测定的主动脉中氧化剂的产生较少，(3)心脏Akt的磷酸化减少，以及(4)主动脉和心脏中诱导型一氧化氮合酶(INOS)的表达减少。在培养的Glrx KO小鼠胚胎成纤维细胞中，与WT细胞相比，过氧化氢刺激后肌动蛋白的S谷胱甘肽解聚作用增强，肌动蛋白解聚作用减弱。此外，在佛波酯刺激的成纤维细胞和RAW 264.7巨噬细胞样细胞中，Glrx siRNA被敲除后产生的氧化剂较少。这些数据表明，在Glrx KO小鼠中，Ang II诱导的氧化剂产生和肥大反应减弱，这可能是由于NADPH氧化酶活性受损所致。
Glutaredoxin-1 (Glrx) is a thioltransferase that regulates protein S-glutathiolation. To elucidate the role of endogenous Glrx in cardiovascular disease, Glrx knockout (KO) mice were infused with angiotensin II (Ang II) for 6 days. After Ang II infusion, body weight and blood pressure were similar between WT and Glrx KO mice. However, compared to WT mice, Glrx KO mice demonstrated (1) less cardiac and aortic medial hypertrophy, (2) less oxidant generation in aorta assessed by dihydroethidium staining and nitrotyrosine, (3) decreased phosphorylation of Akt in the heart, and (4) less expression of inducible NOS (iNOS) in aorta and heart. In cultured embryonic fibroblasts from Glrx KO mice, S-glutathiolation of actin was enhanced and actin depolymerization was impaired after hydrogen peroxide stimulation compared with WT cells. Furthermore, oxidant generation in phorbol ester-stimulated fibroblasts and RAW 264.7 macrophage-like cells was lower with Glrx siRNA knockdown. These data indicate that Ang II-induced oxidant production and hypertrophic responses were attenuated in Glrx KO mice, which may result from impaired NADPH oxidase activation.
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影响因子：
37.8
作者：
Matsui, R;Xu, SQ;Cohen, RA
通讯作者：
Cohen, RA
影响因子：
4.8
作者：
Chrestensen, CA;Starke, DW;Mieyal, JJ
通讯作者：
Mieyal, JJ
影响因子：
7.4
作者：
Meyer, EB;Wells, WW
通讯作者：
Wells, WW
DOI：
10.1073/pnas.96.15.8693
发表时间：
1999-07-20
影响因子：
11.1
作者：
Nunoi, H;Yamazaki, T;Kanegasaki, S
通讯作者：
Kanegasaki, S
影响因子：
4.1
作者：
MANNERVIK, B;AXELSSON, K;HOLMGREN, A
通讯作者：
HOLMGREN, A