Expression and Activity Patterns of Nitric Oxide Synthases and Antioxidant Enzymes Reveal a Substantial Heterogeneity Between Cardiac and Vascular Aging in the Rat
Expression and Activity Patterns of Nitric Oxide Synthases and Antioxidant Enzymes Reveal a Substantial Heterogeneity Between Cardiac and Vascular Aging in the Rat
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一氧化氮合成酶和抗氧化酶的表达和活性模式揭示了大鼠心脏和血管衰老之间的显着异质性
DOI：
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
T. Lüscher
中科院分区：
文献类型：
--
作者：
B. Loo;M. Bachschmid;Ralf Labugger;S. Schildknecht;J. Kilo;R. Hahn;M. Palacios;T. Lüscher
我们研究了衰老和缺血再灌注（I/R）损伤对一氧化氮（•NO）合酶和超氧化物歧化酶（SOD）异构体的表达及活性的影响。为此，我们按照朗根多夫技术对年轻（6个月大）和年老（31 - 34个月大）大鼠的离体心脏进行灌注。在基线灌注30分钟后，离体心脏要么经历20分钟的全心无血流缺血，随后再灌注40分钟，要么进行对照灌注（60分钟常氧灌注）。随着年龄增长，锰超氧化物歧化酶（MnSOD）和铜锌超氧化物歧化酶（Cu,ZnSOD）的表达均未改变，且不受缺血再灌注的影响。然而，超氧化物歧化酶活性从年轻心脏的7.55 ± 0.1单位/毫克蛋白下降到年老心脏的5.94 ± 0.44单位/毫克蛋白（P<0.05）。此外，缺血再灌注导致年轻动物心肌中的酶活性进一步下降（至6.35 ± 0.41单位/毫克蛋白；P<0.05），但年老动物心肌中未出现这种情况。未检测到心肌中蛋白质结合的3 - 硝基酪氨酸水平有变化。内皮型一氧化氮合酶（eNOS）在老年左心室中的表达和活性无论是否有缺血再灌注损伤均未改变。这与从相同动物获取的外周（肾和股）动脉形成鲜明对比，在外周动脉中可以证明内皮型一氧化氮合酶蛋白表达随年龄增长显著增加。无论年龄如何，在外周动脉或左心室中均未检测到诱导型一氧化氮合酶的表达。特别是当与一种急性病理状态相关联，且这种病理状态还局限于一定时间范围时，与血管衰老过程相比，衰老心肌中对于维持氧化还原稳态至关重要的酶的变化似乎不太明显，甚至不存在。这可能表明心血管衰老过程在分子调控方面存在异质性。
We investigated the effects of aging and ischemia–reperfusion (I/R) injury on the expression and activity of nitric oxide (•NO) synthases and superoxide dismutase (SOD) isoforms. To this end we perfused excised hearts from young (6 months old) and old (31–34 months old) rats according to the Langendorff technique. The isolated hearts were, after baseline perfusion for 30 min, either subjected to 20 min of global no-flow ischemia followed by 40 min of reperfusion or were control-perfused (60 min normoxic perfusion). Both MnSOD and Cu,ZnSOD expression remained unchanged with increasing age and remained unaltered by I/R. However, SOD activity decreased from 7.55 ± 0.1 U/mg protein in young hearts to 5.94 ± 0.44 in old hearts (P<0.05). Furthermore, I/R led to a further decrease in enzyme activity (to 6.35 ± 0.41 U/mg protein; P<0.05) in myocardium of young, but not in that of old animals. No changes in myocardial protein-bound 3-nitrotyrosine levels could be detected. Endothelial NOS (eNOS) expression and activity remained unchanged in aged left ventricles, irrespective of I/R injury. This was in steep contrast to peripheral (renal and femoral) arteries obtained from the same animals where a marked age-associated increase of eNOS protein expression could be demonstrated. Inducible NOS expression was undetectable either in the peripheral arteries or in the left ventricle, irrespective of age. In particular when associated with an acute pathology, which is furthermore limited to a certain time frame, changes in the aged myocardium with respect to enzymes crucially involved in maintaining the redox homeostasis, seem to be much less pronounced or even absent compared to the vascular aging process. This may point to heterogeneity in the molecular regulation of the cardiovascular aging process.
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影响因子：
7.4
作者：
Antunes, F;Han, D;Cadenas, E
通讯作者：
Cadenas, E
DOI：
10.1073/pnas.93.21.11853
发表时间：
1996-10-15
影响因子：
11.1
作者：
MacMillanCrow, LA;Crow, JP;Thompson, JA
通讯作者：
Thompson, JA
影响因子：
3.9
作者：
BECKMAN, JS;ISCHIROPOULOS, H;TSAI, M
通讯作者：
TSAI, M
影响因子：
20.1
作者：
Brahmajothi, MV;Campbell, DL
通讯作者：
Campbell, DL
离体大鼠心脏缺血/再灌注期间 MnSOD 缺乏变化。
影响因子：
5
作者：
Subramanian,R;Volovsek,A;Ho,YS
通讯作者：
Ho,YS