Skeletal muscle as an endogenous nitrate reservoir.
Skeletal muscle as an endogenous nitrate reservoir.
复制标题
DOI：
10.1016/j.niox.2015.02.145
复制
发表时间：
2015-05-01
影响因子：
3.9
通讯作者：
Schechter, Alan N.
中科院分区：
文献类型：
--
作者：
Piknova, Barbora;Park, Ji Won;Swanson, Kathryn M.;Dey, Soumyadeep;Noguchi, Constance Tom;Schechter, Alan N.
一氧化氮合酶（NOS）家族的酶在氧存在下从精氨酸形成一氧化氮（NO）。在氧可用性降低时，NO也通过细菌和哺乳动物的铁蝶呤蛋白在两步过程中从硝酸盐产生，并且还通过多种五配位亚铁血红素蛋白直接从亚硝酸盐产生。哺乳动物NO循环还涉及NO直接氧化成亚硝酸盐，以及NO和亚硝酸盐通过含氧亚铁血红素蛋白直接氧化成硝酸盐。肝脏和血液被认为是哺乳动物NO代谢的活跃场所，已经测定了包括人类在内的几种哺乳动物的肝脏和血液中的亚硝酸盐和硝酸盐浓度。然而，在NO循环的分析中，通常没有考虑骨骼肌的大组织块，尽管其长期已知存在显著水平的活性神经元NOS（nNOS或NOS 1）。我们假设骨骼肌参与NO循环，并且由于其NO氧化血红素蛋白，氧肌红蛋白，具有高浓度的硝酸根离子。我们测量了大鼠和小鼠腿部骨骼肌中的亚硝酸盐和硝酸盐浓度，发现与肝脏相比，硝酸盐浓度异常高，但亚硝酸盐水平相似。肌肉中的硝酸盐储库很容易通过血液进入，因此硝酸盐可被运输到内脏器官，在那里它可以被还原为亚硝酸盐和NO。与对照组相比，nNOS−/−小鼠骨骼肌和血液中的硝酸盐水平显着降低，这进一步支持了我们的假设。虽然肌肉中黄嘌呤氧化还原酶的硝酸还原酶活性低于肝脏，但鉴于其总质量和硝酸盐的高基础水平，肌肉中的残留活性可能非常重要。我们认为，骨骼肌参与整体NO代谢，作为一个硝酸盐水库，直接形成亚硝酸盐和NO，并确定其他器官中的硝酸盐水平。
The nitric oxide synthase (NOS) family of enzymes form nitric oxide (NO) from arginine in the presence of oxygen. At reduced oxygen availability NO is also generated from nitrate in a two step process by bacterial and mammalian molybdopterin proteins, and also directly from nitrite by a variety of five-coordinated ferrous hemoproteins. The mammalian NO cycle also involves direct oxidation of NO to nitrite, and both NO and nitrite to nitrate by oxy-ferrous hemoproteins. The liver and blood are considered the sites of active mammalian NO metabolism and nitrite and nitrate concentrations in the liver and blood of several mammalian species, including human, have been determined. However, the large tissue mass of skeletal muscle had not been generally considered in the analysis of the NO cycle, in spite of its long-known presence of significant levels of active neuronal NOS (nNOS or NOS1). We hypothesized that skeletal muscle participates in the NO cycle and, due to its NO oxidizing heme protein, oxymyoglobin, has high concentrations of nitrate ions. We measured nitrite and nitrate concentrations in rat and mouse leg skeletal muscle and found unusually high concentrations of nitrate but similar levels of nitrite, when compared to the liver. The nitrate reservoir in muscle is easily accessible via the bloodstream and therefore nitrate is available for transport to internal organs where it can be reduced to nitrite and NO. Nitrate levels in skeletal muscle and blood in nNOS−/− mice were dramatically lower when compared with controls, which support further our hypothesis. Although the nitrate reductase activity of xanthine oxidoreductase in muscle is less than that of liver, the residual activity in muscle could be very important in view of its total mass and the high basal level of nitrate. We suggest that skeletal muscle participates in overall NO metabolism, serving as a nitrate reservoir, for direct formation of nitrite and NO, and for determining levels of nitrate in other organs.
登录
查看更多内容
DOI：
10.1016/j.niox.2009.07.002
发表时间：
2009-09
期刊：
Nitric oxide : biology and chemistry
影响因子：
--
作者：
Hall CN;Garthwaite J
通讯作者：
Garthwaite J
影响因子：
13.8
作者：
Brunori, M
通讯作者：
Brunori, M
影响因子：
6.6
作者：
Milsom, Alexandra B.;Fernandez, Bernadette O.;Feelisch, Martin
通讯作者：
Feelisch, Martin
影响因子：
7.1
作者：
ECHEVARNE, C;RENERRE, M;LABAS, R
通讯作者：
LABAS, R
影响因子：
82.9
作者：
Cosby, K;Partovi, KS;Gladwin, MT
通讯作者：
Gladwin, MT