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| Status |
Public on Oct 21, 2010 |
| Title |
Increased hemoglobin expression in NASH livers |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
BACKGROUND & AIMS: 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 to investigate whether hemoglobin is expressed in hepatocytes and how it is related to oxidative stress in NASH patients. METHODS: Microarray was performed to identify differentially expressed genes in NASH. Quantitative real time PCR (qRT-PCR) was used to examine gene expression levels. Western blotting and immunofluorescence staining were employed to examine hemoglobin proteins. Flow cytometry was used to measure intracellular oxidative stress. RESULTS: Analysis of microarray gene expression data has revealed a significant increase in the expression of hemoglobin alpha (HBA1) and beta (HBB) in liver biopspies from NASH patients. Increased hemoglobin expression in NASH was validated by qRT-PCR. However, the expression of erythrocyte specific marker genes such as SPTA, SPTB, GYPA, GATA1, and ALAS2 did not change, 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, induced a dose dependent increase in HBA1 expression in HepG2 cells. Intriguingly, forced hemoglobin expression suppressed oxidative stress. CONCLUSIONS: Oxidative stress upregulates hemoglobin expression in hepatocytes. Suppression of oxidative stress by hemoglobin could be a mechanism to protect hepatocytes from oxidative damage. These findings suggest that hemoglobin is an inducible antioxidant in hepatocytes in response to increased oxidative stress as found in NASH livers.
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| Overall design |
Twelve biopsy diagnosed NASH patients were included in this study. For control groups, total RNA from 5 different subjects were purchased from ADMET. These subjects are free from liver disease.
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| Contributor(s) |
Baker SS, Baker RD, Liu W, Nowak NJ, Zhu L |
| Citation(s) |
21931690, 25938357 |
| Submission date |
Oct 19, 2010 |
| Last update date |
Oct 11, 2019 |
| Contact name |
Susan Baker |
| E-mail(s) |
sbaker@upa.chob.edu, lixinzhu@buffalo.edu
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| Organization name |
SUNY at Buffalo
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| Department |
Pediatrics
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| Lab |
Digestive Diseases and Nutrition Center Research Laboratory
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| Street address |
3435 Main street, 422 BRB
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| City |
Buffalo |
| State/province |
NY |
| ZIP/Postal code |
14214 |
| Country |
USA |
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| Platforms (1) |
| GPL2895 |
GE Healthcare/Amersham Biosciences CodeLink Human Whole Genome Bioarray |
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| Samples (17)
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| GSM435821 |
Global gene expression of NASH patients, P53 |
| GSM435822 |
Global gene expression of NASH patients, P55 |
| GSM435823 |
Global gene expression of NASH patient, P59 |
| GSM435824 |
Global gene expression of NASH patients, P35 |
| GSM435825 |
Global gene expression of NASH patients, P37 |
| GSM435826 |
Global gene expression of NASH patients, P40 |
| GSM435827 |
Global gene expression of NASH patients, P41 |
| GSM435828 |
Global gene expression of NASH patients, Normal control A486 |
| GSM435833 |
Global gene expression of NASH patients, normal control A643 |
| GSM610690 |
Global gene expression of NASH patient, P34 |
| GSM610691 |
Global gene expression of NASH patients, P51 |
| GSM610695 |
Global gene expression of NASH patients, P62 |
| GSM610696 |
Global gene expression of NASH patients, P64 |
| GSM610717 |
Global gene expression of NASH patients, P66 |
| GSM610718 |
Global gene expression of NASH patients, normal control A99 |
| GSM610737 |
Global gene expression of NASH patients, normal control A107 |
| GSM610738 |
Global gene expression of NASH patients, normal control A154 |
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| Relations |
| BioProject |
PRJNA132303 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE24807_RAW.tar |
37.3 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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