Digestive Diseases and Nutrition Center, Department of Pediatrics, The State University of New York at Buffalo, Buffalo, New York, United States of America.
PLoS One. 2011;6(9):e24363. doi: 10.1371/journal.pone.0024363. Epub 2011 Sep 12.
Recent studies revealed that hemoglobin is expressed in some non-erythrocytes and it suppresses oxidative stress when overexpressed. Oxidative stress plays a critical role in the pathogenesis of non-alcoholic steatohepatitis (NASH). This study was designed to investigate whether hemoglobin is expressed in hepatocytes and how it is related to oxidative stress in NASH patients. Analysis of microarray gene expression data revealed a significant increase in the expression of hemoglobin alpha (HBA1) and beta (HBB) in liver biopsies from NASH patients. Increased hemoglobin expression in NASH was validated by quantitative real time PCR. However, the expression of hematopoietic transcriptional factors and erythrocyte specific marker genes were not increased, indicating that increased hemoglobin expression in NASH was not from erythropoiesis, but could result from increased expression in hepatocytes. Immunofluorescence staining demonstrated positive HBA1 and HBB expression in the hepatocytes of NASH livers. Hemoglobin expression was also observed in human hepatocellular carcinoma HepG2 cell line. Furthermore, treatment with hydrogen peroxide, a known oxidative stress inducer, increased HBA1 and HBB expression in HepG2 and HEK293 cells. Importantly, hemoglobin overexpression suppressed oxidative stress in HepG2 cells. We concluded that hemoglobin is expressed by hepatocytes and oxidative stress upregulates its expression. Suppression of oxidative stress by hemoglobin could be a mechanism to protect hepatocytes from oxidative damage in NASH.
最近的研究表明，血红蛋白在一些非红细胞中表达，并且在过表达时抑制氧化应激。氧化应激在非酒精性脂肪性肝炎（NASH）的发病机制中起着关键作用。本研究旨在研究血红蛋白是否在肝细胞中表达，以及它与 NASH 患者的氧化应激有何关系。微阵列基因表达数据分析显示，NASH 患者肝活检中血红蛋白α（HBA1）和β（HBB）的表达显著增加。通过实时定量 PCR 验证了 NASH 中血红蛋白表达的增加。然而，造血转录因子和红细胞特异性标记基因的表达并没有增加，这表明 NASH 中血红蛋白表达的增加不是来自红细胞生成，而是可能来自肝细胞的表达增加。免疫荧光染色显示 NASH 肝脏的肝细胞中 HBA1 和 HBB 表达呈阳性。在人肝癌 HepG2 细胞系中也观察到血红蛋白表达。此外，用已知的氧化应激诱导剂过氧化氢处理，增加了 HepG2 和 HEK293 细胞中 HBA1 和 HBB 的表达。重要的是，血红蛋白过表达抑制了 HepG2 细胞中的氧化应激。我们得出结论，血红蛋白由肝细胞表达，氧化应激上调其表达。血红蛋白对氧化应激的抑制可能是保护 NASH 肝细胞免受氧化损伤的一种机制。
