Man Kwun-Nok Mimi, Philipsen Sjaak, Tan-Un Kian Cheng
University of Hong Kong, School of Biological Sciences, 6N-09, Kadoorie Biological Sciences Building, Pokfulam, Hong Kong SAR.
Toxicol Lett. 2008 Dec 15;183(1-3):36-44. doi: 10.1016/j.toxlet.2008.09.015. Epub 2008 Oct 1.
Cytoglobin (Cygb) is a recently discovered hexacoordinate globin protein with a yet undefined function. It was found to be up-regulated in toxin-induced liver fibrosis and during hypoxic conditions [Fago, A., Hundahl, C., Malte, H., Weber, R.E., 2004. Functional properties of neuroglobin and cytoglobin. Insights into the ancestral physiological roles of globins. IUBMB Life 56, 689-696; Fordel, E., Thijs, L., Martinet, W., Schrijvers, D., Moens, L., Dewilde, S., 2007. Anoxia or oxygen and glucose deprivation in SH-SY5Y cells: a step closer to the unraveling of neuroglobin and cytoglobin functions. Gene 398, 114-122; Guo, X., Philipsen, S., Tan-Un, K.C., 2007. Study of the hypoxia-dependent regulation of human CYGB gene. Biochem. Biophys. Res. Commun. 364, 145-150; Li, D., Chen, X.Q., Li, W.J., Yang, Y.H., Wang, J.Z., Yu, A.C., 2007. Cytoglobin up-regulated by hydrogen peroxide plays a protective role in oxidative stress. Neurochem. Res. 32, 1375-1380]. Cygb is expressed ubiquitously in most tissues but its subcellular localization in certain cell types (e.g. hepatocytes) is still controversial. In this study we investigated the localization of Cygb protein in mouse tissues, its expression pattern in response to carbon tetrachloride (CCl(4)) challenge and that during CCl(4)-induced liver fibrosis in order to delineate the functional property of Cygb. We found that it is expressed in fibroblasts in various organs and in the hepatic stellate cells. Cygb mRNA expression is up-regulated by more than 3.5-fold 24h after administration of CCl(4). At 48h post-administration, the expression of procollagen I alpha 1 mRNA was increased by over 7.6-fold. The increase in collagen expression after CCl(4) insult was also evident at the protein level. We found that the number of Cygb-expressing cells increased through the development of CCl(4)-induced liver fibrosis. It may be possible that Cygb is an early biomarker for liver fibrosis.
细胞珠蛋白（Cygb）是一种最近发现的六配位珠蛋白，其功能尚未明确。研究发现，在毒素诱导的肝纤维化以及低氧条件下，细胞珠蛋白表达上调[法戈，A.，洪达尔，C.，马尔特，H.，韦伯，R.E.，2004年。神经珠蛋白和细胞珠蛋白的功能特性。对珠蛋白祖先生理作用的深入了解。国际生物化学与分子生物学联盟生活56，689 - 696；福尔德尔，E.，蒂伊斯，L.，马蒂内，W.，施里弗斯，D.，莫恩斯，L.，德维尔德，S.，2007年。SH - SY5Y细胞中的缺氧或氧与葡萄糖剥夺：向揭示神经珠蛋白和细胞珠蛋白功能迈进了一步。基因398，114 - 122；郭，X.，菲利普森，S.，谭恩，K.C.，2007年。人CYGB基因缺氧依赖性调控的研究。生物化学与生物物理研究通讯364，145 - 150；李，D.，陈，X.Q.，李，W.J.，杨，Y.H.，王，J.Z.，于，A.C.，2007年。过氧化氢上调的细胞珠蛋白在氧化应激中起保护作用。神经化学研究32，1375 - 1380]。细胞珠蛋白在大多数组织中普遍表达，但其在某些细胞类型（如肝细胞）中的亚细胞定位仍存在争议。在本研究中，我们调查了细胞珠蛋白在小鼠组织中的定位、其对四氯化碳（CCl₄）攻击的反应表达模式以及在CCl₄诱导的肝纤维化过程中的表达模式，以阐明细胞珠蛋白的功能特性。我们发现它在各种器官的成纤维细胞和肝星状细胞中表达。给予CCl₄后24小时，细胞珠蛋白mRNA表达上调超过3.5倍。给药后48小时，I型前胶原α1 mRNA的表达增加超过7.6倍。在蛋白质水平上，CCl₄损伤后胶原蛋白表达的增加也很明显。我们发现，随着CCl₄诱导的肝纤维化发展，表达细胞珠蛋白的细胞数量增加。细胞珠蛋白有可能是肝纤维化的早期生物标志物。
