Using high-resolution immuno-electron microscopy the steady-state subcellular distribution of tyrosine-nitrated proteins in different cells and tissues was evaluated. In quiescent eosinophils and neutrophils in the bone marrow intracellular nitrated proteins were mainly restricted to the peroxidase-containing secretory granules. The inducible nitric oxide synthase (iNOS) was expressed in the same granules. Proteins nitrated on tyrosine residues were also abundant in the cytosol of circulating erythrocytes. In the vasculature, nitrated proteins were mainly located in mitochondria and endoplasmic reticulum of the endothelial cells, fibroblasts, and smooth muscle cells. Endogenous nitrated proteins were also found in chondrocytes in cartilage, where it was typically associated with the cytoplasmic interface of the endoplasmic reticulum membrane. Nitrated proteins were also prominent in the peroxisomes of liver hepatocytes and of secretory cells in the lacrimal gland. Challenge of mouse dendritic cells with lipopolysaccharide induced iNOS protein expression in cytosol and peroxisomes and was associated with an increased 3-nitrotyrosine formation in cytosol, mitochondria, and peroxisomes. These data indicate that nitric oxide-dependent protein tyrosine nitration is a physiologically relevant process localized within specific subcellular compartments in close proximity to iNOS and to enzymes capable of peroxidative chemistry and reactive oxygen species production.

中文翻译：

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酪氨酸硝化蛋白的亚细胞定位是由产生活性氧的酶和与一氧化氮合酶的接近性决定的。

使用高分辨率的免疫电子显微镜，评估了酪氨酸硝化蛋白质在不同细胞和组织中的稳态亚细胞分布。在静止的嗜酸性粒细胞和嗜中性粒细胞的骨髓中，细胞内的硝化蛋白主要局限于含过氧化物酶的分泌颗粒。诱导型一氧化氮合酶（iNOS）在相同的颗粒中表达。酪氨酸残基上被硝化的蛋白质在循环红细胞的细胞质中也很丰富。在脉管系统中，硝化蛋白主要位于内皮细胞，成纤维细胞和平滑肌细胞的线粒体和内质网中。在软骨的软骨细胞中还发现了内源性硝酸化蛋白，该蛋白通常与内质网膜的细胞质界面有关。硝化蛋白在肝肝细胞和泪腺分泌细胞的过氧化物酶体中也很明显。用脂多糖攻击小鼠树突状细胞可诱导iNOS蛋白在细胞质和过氧化物酶体中表达，并与细胞质，线粒体和过氧化物酶体中3-硝基酪氨酸的形成增加有关。这些数据表明，一氧化氮依赖性蛋白酪氨酸硝化是生理相关的过程，位于iNOS和能够过氧化化学反应和产生活性氧的酶附近的特定亚细胞区室中。用脂多糖攻击小鼠树突状细胞可诱导iNOS蛋白在细胞质和过氧化物酶体中表达，并与细胞质，线粒体和过氧化物酶体中3-硝基酪氨酸的形成增加有关。这些数据表明，一氧化氮依赖性蛋白酪氨酸硝化是生理相关的过程，位于iNOS和能够过氧化化学反应和产生活性氧的酶附近的特定亚细胞区室中。用脂多糖攻击小鼠树突状细胞可诱导iNOS蛋白在细胞质和过氧化物酶体中表达，并与细胞质，线粒体和过氧化物酶体中3-硝基酪氨酸的形成增加有关。这些数据表明，一氧化氮依赖性蛋白酪氨酸硝化是生理相关的过程，位于iNOS和能够过氧化化学反应和产生活性氧的酶附近的特定亚细胞区室中。