Characterization of adult α- and β-globin elevated by hydrogen peroxide in cervical cancer cells that play a cytoprotective role against oxidative insults

Hemoglobin (Hgb) is the main oxygen and carbon dioxide carrier in cells of erythroid lineage and is responsible for oxygen delivery to the respiring tissues of the body. However, Hgb is also expressed in nonerythroid cells. In the present study, the expression of Hgb in human uterine cervix carcinom...

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Published in:	PloS one 2013, Vol.8 (1), p.e54342
Main Authors:	Li, Xiaolei, Wu, Zhiqiang, Wang, Yao, Mei, Qian, Fu, Xiaobing, Han, Weidong
Format:	Article
Language:	eng
Subjects:	alpha-Globins - genetics alpha-Globins - metabolism Annexin V Antioxidants Apoptosis Base Sequence beta-Globins - genetics beta-Globins - metabolism Biology Cancer Carbon dioxide Caspase Caspase-3 Cell Line, Tumor Cervical cancer Cervical carcinoma Cytometry Ectopic expression Erythrocytes Female Flow cytometry Gene expression Gene Expression Regulation, Neoplastic - drug effects HEK293 Cells HeLa Cells Hemoglobin Hemopoiesis Hospitals HT29 Cells Humans Hydrogen Hydrogen peroxide Hydrogen Peroxide - metabolism Hydrogen Peroxide - pharmacology Immunoblotting Immunology Impact damage Kinases L-Lactate dehydrogenase Lactate dehydrogenase Lactic acid Life sciences MCF-7 Cells Medicine Microscopy, Fluorescence Middle Aged Molecular biology Mutants Ovarian cancer Oxidants - metabolism Oxidants - pharmacology Oxidative Stress Oxygen Pathogenesis Polymerase chain reaction Proteins Reactive oxygen species Reactive Oxygen Species - metabolism Red blood cells Reverse Transcriptase Polymerase Chain Reaction RNA-directed DNA polymerase Rodents Studies Superoxides - metabolism Thyroid gland Tissues Transcription factors Tumor cell lines Tumors Uterine cancer Uterine Cervical Neoplasms - genetics Uterine Cervical Neoplasms - metabolism Uterine Cervical Neoplasms - pathology Uterus
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Summary:	Hemoglobin (Hgb) is the main oxygen and carbon dioxide carrier in cells of erythroid lineage and is responsible for oxygen delivery to the respiring tissues of the body. However, Hgb is also expressed in nonerythroid cells. In the present study, the expression of Hgb in human uterine cervix carcinoma cells and its role in cervical cancer were investigated. The expression level of Hgb in cervical cancer tissues was assessed by quantitative reverse transcriptase-PCR (qRT-PCR). We applied multiple methods, such as RT-PCR, immunoblotting, and immunohistochemical analysis, to confirm Hgb expression in cervical cancer cells. The effects of ectopic expression of Hgb and Hgb mutants on oxidative stress and cell viability were investigated by cellular reactive oxygen species (ROS) analysis and lactate dehydrogenase (LDH) array, respectively. Both Annexin V staining assay by flow cytometry and caspase-3 activity assay were used, respectively, to evaluate cell apoptosis. qRT-PCR analysis showed that Hgb-α- (HBA1) and Hgb-β-globin (HBB) gene expression was significantly higher in cervical carcinoma than in normal cervical tissues, whereas the expression of hematopoietic transcription factors and erythrocyte specific marker genes was not increased. Immunostaining experiments confirmed the expression of Hgb in cancer cells of the uterine cervix. Hgb mRNA and protein were also detected in the human cervical carcinoma cell lines SiHa and CaSki, and Hgb expression was up-regulated by hydrogen peroxide-induced oxidative stress. Importantly, ectopic expression of wild type HBA1/HBB or HBA1, rather than mutants HBA1(H88R)/HBB(H93R) unable to bind hemo, suppressed oxidative stress and improved cell viability. The present findings show for the first time that Hgb is expressed in cervical carcinoma cells and may act as an antioxidant, attenuating oxidative stress-induced damage in cervical cancer cells. These data provide a significant impact not only in globin biology but also in understanding of cervical cancer pathogenesis associated with oxidative stress.
ISSN:	1932-6203 1932-6203