Functional analysis of cytoglobin that is expressed and induced in liver cirrhosis

细胞珠蛋白是一类新的六配位珠蛋白超家族，最近通过蛋白质组学方法在大鼠肝星状细胞（肝脏中一种独特的成纤维细胞）中发现。与血红蛋白、肌红蛋白和神经红蛋白不同，细胞红蛋白在肝脏、胰腺、肾脏、脾脏、肠和肺等器官中普遍表达，但其具体位置尚不清楚。免疫组织化学和免疫电镜显示，细胞红蛋白独特地定位于内脏器官的成纤维细胞样细胞，即维生素a储存细胞谱系，但不在上皮细胞、内皮细胞、肌肉细胞、血细胞、巨噬细胞和真皮成纤维细胞中。在胰腺和肾脏纤维化病变中，活化的成纤维细胞样细胞或肌成纤维细胞数量增加，细胞红蛋白表达上调。在培养的肝星状细胞中，血清、血小板源性生长因子- bb和转化生长因子- β 1刺激可增强细胞红蛋白的表达。这些结果表明，细胞红蛋白是一种独特的组织血红蛋白，定位于内脏成纤维细胞谱系，并可能在纤维化器官疾病中发挥作用。通过纯化和结晶的细胞红蛋白获得的其他实验表明，这种蛋白质以类似于肌红蛋白的方式结合氧、一氧化氮和一氧化碳。因此，细胞红蛋白是一种新的球蛋白，在内脏肌成纤维细胞的氧运输中起作用，相反，肌红蛋白似乎是肌肉细胞特异性的氧载体。

Cytoglobin consists of a new class of hexacoordinate globin superfamily, which was recently discovered by a proteomics approach for the rat hepatic stellate cell, an unique fibroblastic cell in the liver. Unlike hemoglobin, myoglobin and neuroglobin, cytoglobin is ubiquitously expressed in several organs including the liver, pancreas, kidney, spleen, intestine and lung, although its detailed localization is unclarified. Immunohistochemistry and immunoelectronmicroscopy revealed that cytoglobin is uniquely localized in fibroblast-like cells in splanchnic organs, namely vitamin A-storing cell lineage, but neither in epithelial cells, endothelial cells, muscle cells, blood cells, macrophages, nor dermal fibroblasts. Expression of cytoglobin was upregulated in fibrotic lesions of pancreas and kidney in which activated fibroblast-like cells or myofibroblasts increased in number. In cultured hepatic stellate cells, cytoglobin expression was augmented by the stimulation with serum, platelet-derived growth factor-BB and transforming growth factor-beta 1. These results indicate that cytoglobin is a tissue hemoglobin uniquely localized in splanchnic fibroblastic cell lineage and may play a role in fibrotic organ disorder. Additional experiments obtained by purified and crystallized cytoglobin revealed that this protein bind oxygen, nitric oxide and carbon monoxide in a manner similar to myoglobin. Thus, cytoglobin is a novel globin that play a role in oxygen transport in visceral myofibroblasts and in contrast myoglobin seems to be a muscle cell-specific oxygen carrier.