Role of superoxide-nitric oxide interactions in the accelerated age-related loss of muscle mass in mice lacking Cu,Zn superoxide dismutase.
Role of superoxide-nitric oxide interactions in the accelerated age-related loss of muscle mass in mice lacking Cu,Zn superoxide dismutase.
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DOI：
10.1111/j.1474-9726.2011.00709.x
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发表时间：
2011-10
期刊：
影响因子：
7.8
通讯作者：
Jackson MJ
中科院分区：
文献类型：
--
作者：
Sakellariou GK;Pye D;Vasilaki A;Zibrik L;Palomero J;Kabayo T;McArdle F;Van Remmen H;Richardson A;Tidball JG;McArdle A;Jackson MJ
缺乏铜，锌超氧化物歧化酶（SOD 1）的小鼠表现出加速的，与年龄相关的肌肉质量损失。缺乏SOD 1可能导致超氧化物增加，一氧化氮（NO）减少，过氧亚硝酸盐增加，每一种都可能引发肌纤维损失。来自野生型（WT）和Sod 1 −/−小鼠的趾短屈肌的单个肌纤维负载有NO敏感性（4-氨基-5-甲氨基-2 ′，7 ′-二氟荧光素二乙酸酯，DAF-FM）和超氧化物敏感性（二氢乙锭，DHE）探针。测定腓肠肌SOD酶、一氧化氮合酶（NOS）和3-硝基酪氨酸（3-NT）含量。缺乏SOD 1并没有增加休息时超氧化物的可用性，因为与WT小鼠相比，在Sod 1 −/−小鼠的纤维中没有观察到DHE形成乙锭或2-羟基乙锭（2-HE）的增加。与野生型小鼠相比，来自Sod 1 −/−小鼠的纤维具有降低的NO可用性（降低的DAF-FM荧光），肌肉蛋白中的3-NT增加，表明过氧亚硝酸盐形成增加和过氧化物氧还蛋白V（过氧亚硝酸盐还原酶）含量增加。与野生型小鼠的肌纤维相比，Sod 1 −/−小鼠的肌纤维在收缩时产生的超氧化物大大减少。NOS的抑制并不影响休息或收缩时WT或Sod 1 −/−小鼠纤维中DHE的氧化，但过表达nNOS的转基因小鼠显示出DAF-FM荧光增加，静息肌纤维中DHE氧化减少。结论是，肌纤维中过氧亚硝酸盐的形成是Sod 1 −/−小鼠缺乏SOD 1的主要影响，可能导致该模型中的纤维损失，NO调节肌肉中超氧化物的可用性和过氧亚硝酸盐的形成。
Mice lacking Cu,Zn superoxide dismutase (SOD1) show accelerated, age-related loss of muscle mass. Lack of SOD1 may lead to increased superoxide, reduced nitric oxide (NO), and increased peroxynitrite, each of which could initiate muscle fiber loss. Single muscle fibers from flexor digitorum brevis of wild-type (WT) and Sod1−/− mice were loaded with NO-sensitive (4-amino-5-methylamino-2′,7′-difluorofluorescein diacetate, DAF-FM) and superoxide-sensitive (dihydroethidium, DHE) probes. Gastrocnemius muscles were analyzed for SOD enzymes, nitric oxide synthases (NOS), and 3-nitrotyrosine (3-NT) content. A lack of SOD1 did not increase superoxide availability at rest because no increase in ethidium or 2-hydroxyethidium (2-HE) formation from DHE was seen in fibers from Sod1−/− mice compared with those from WT mice. Fibers from Sod1−/− mice had decreased NO availability (decreased DAF-FM fluorescence), increased 3-NT in muscle proteins indicating increased peroxynitrite formation and increased content of peroxiredoxin V (a peroxynitrite reductase), compared with WT mice. Muscle fibers from Sod1−/− mice showed substantially reduced generation of superoxide in response to contractions compared with fibers from WT mice. Inhibition of NOS did not affect DHE oxidation in fibers from WT or Sod1−/− mice at rest or during contractions, but transgenic mice overexpressing nNOS showed increased DAF-FM fluorescence and reduced DHE oxidation in resting muscle fibers. It is concluded that formation of peroxynitrite in muscle fibers is a major effect of lack of SOD1 in Sod1−/− mice and may contribute to fiber loss in this model, and that NO regulates superoxide availability and peroxynitrite formation in muscle.
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影响因子：
5.5
作者：
Fink, B;Laude, K;Dikalov, S
通讯作者：
Dikalov, S
DOI：
10.1073/pnas.0306706101
发表时间：
2004-03-23
影响因子：
11.1
作者：
Bryan, NS;Rassaf, T;Feelisch, M
通讯作者：
Feelisch, M
DOI：
10.1152/ajpcell.2001.280.3.c621
发表时间：
2001-03-01
影响因子：
5.5
作者：
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通讯作者：
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影响因子：
5.8
作者：
Andrés, D;Sanz, N;Cascales, M
通讯作者：
Cascales, M
DOI：
10.1111/j.1749-6632.2002.tb02104.x
发表时间：
2002-01-01
期刊：
INCREASING HEALTHY LIFE SPAN: CONVENTIONAL MEASURES AND SLOWING THE INNATE AGING PROCESS
影响因子：
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作者：
Melov, S
通讯作者：
Melov, S