The human haptoglobin gene: transcriptional regulation during development and acute phase induction
Open accessAbstract
Haptoglobin is a plasma protein scarcely present in fetal but abundant in adult serum, where it is present at a concentration of approximately 150 mg/100 ml. In this paper we show by run-on experiments that the haptoglobin (Hp) gene is actively transcribed in adult but not in fetal liver nuclei. Studies with established cell lines indicate that the Hp gene is expressed in the hepatoma cells HepG2 but not in the hepatoma cell line Hep3B nor in HeLa cells. Plasmids carrying various segments of the 5' flanking region of the Hp gene fused to the chloramphenicol acetyl transferase (CAT) gene direct CAT transcription when introduced into HepG2 but are inactive in Hep3B and in HeLa cells, thus behaving like the resident chromosomal Hp gene. Deletion analysis defines a region, upstream to the transcription initiation site, essential for cell-specific expression. The Hp gene is induced in Hep3B cells by treatment with supernatant from LPS-stimulated monocytes (SMS), in a manner mimicking the acute phase reaction. We characterize the DNA segment necessary and sufficient for cell-specific expression of the Hp-CAT constructions in HepG2 and show that the same segment is also sufficient for acute phase induction in Hep3B.
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Haptoglobin binds free hemoglobin after hemolysis to prevent iron loss through urine and kidney damage.
“Haptoglobin is a tetrachain (α2β2) glycoprotein that binds free hemoglobin following hemolysis as a means to prevent loss of iron through urinary excretion and subsequent kidney damage [7].”
From A battle for iron: host sequestration and Staphylococcus aureus acquisition (2012) · cites this paper as [7]
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BackgroundTadashi, Y., Ogawa, M., Murata, A., Ohmachi, Y., Takushi, Y., Takesada, M., & Matsubara, K. (1993) · Gene · doi:10.1016/0378-1119(93)90306-n · Cited by 27 · see citing works
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“For example, the IL-6-responsive acute-phase gene Hp (41) has been shown along with another c3-eQTL Hpx to prevent hemoglobin-mediated oxidative damage by promoting clearance of hemoglobin released as a consequence of red blood cell turnover or hemolysis (6, 15) via scavenger receptors (8, 27, 57).”
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Haptoglobin and Hemopexin in Heme Detoxification and Iron Recycling
Chiabrando, D., Vinchi, F., Fiorito, V., & Tolosano, E. (2011) · InTech eBooks · doi:10.5772/18241 · Cited by 23 · see citing works
“…at three levels: (i) developmental control, responsible for the lack of expression in fetal liver; (ii)tissue-specific control, responsible for the selectivity of the expression of the gene in the hepatocyte; (iii)modulation of its expression during the acute phase reaction (Oliviero et al., 1987).”
BackgroundInfluentialAcute‐phase proteins in perinatal human plasma
Liberatori, S., Bini, L., Felice, C. D., Magi, B., Marzocchi, B., Raggiaschi, R., PALLINI, V., & Bracci, R. (1997) · Electrophoresis · doi:10.1002/elps.1150180331 · Cited by 23 · see citing works
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Haptoglobin gene expression in human glioblastoma cell lines
Sanchez, D. J., Armstrong, L., Aguilar, R., Adrian, G. S., Haro, L. S., & Martinez, A. O. (2001) · Neuroscience Letters · doi:10.1016/s0304-3940(01)01748-7 · Cited by 21 · see citing works
C-reactive protein (CRP) of the syrian hamster
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Expression of haptoglobin in human keratinocytes and Langerhans cells
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Stimulation of the Acute-Phase Response in Simian Virus 40-Hepatocyte Cell Lines
Liao, W. S. ‐., Ma, K. T., Woodworth, C. D., Mengel, L., & Isom, H. C. (1989) · Molecular and Cellular Biology · doi:10.1128/mcb.9.7.2779 · Cited by 19 · see citing works
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Haptoglobin Function and Regulation in Autoimmune Diseases
Galicia, G., & L., J. (2011) · InTech eBooks · doi:10.5772/22483 · Cited by 17 · see citing works
“Increased production of Hp is the result of transcriptional activation of the Hp gene (Baumann & Jahreis, 1983; Oliviero et al., 1987) by pro-inflammatory cytokines such as interleukin(IL)-1, IL-6, and Tumor Necrosis factor (TNF) (Baumann et al., 1989).”
BackgroundAbah, S. E., Burté, F., Marquet, S., Brown, B. J., Akinkunmi, F., Oyinloye, G., Afolabi, N. K., Omokhodion, S., Lagunju, I. A., Shokunbi, W. A., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-35944-w · Cited by 16 · see citing works
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“The major inducer of the expression of Hp is IL-6, which is produced through the activities of the primary cytokines TNF-α and IL-1 [19].”
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Akinbosede, D., Chizea, R., & Hare, S. (2022) · Microbial Cell · doi:10.15698/mic2022.04.775 · Cited by 13 · see citing works
“glycoprotein that is reported at an average concentration of 150 mg/mL in human adults [10].”
BackgroundRabbit serum amyloid a gene: Cloning, characterization and sequence analysis
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McCarthy, M. E., Buhimschi, C. S., Hardy, J. T., Dulay, A. T., Laky, C. A., Bahtiyar, M. O., Papanna, R. M., Zhao, G., & Buhimschi, I. A. (2017) · Placenta · doi:10.1016/j.placenta.2017.12.017 · Cited by 12 · see citing works
Developmental regulation of expression of rabbit C-reactive protein and serum amyloid A genes
Rygg, M., Alstad, H. K., & Marhaug, G. O. (1996) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/0167-4781(96)00019-x · Cited by 12 · see citing works
Won, K., & Baumann, H. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.8.3965-3978.1990 · Cited by 12 · see citing works
“(20) (42) (21) (2) (46) 12 27 -139 -152 -51 -108 -159 -61”
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Identification of a Transcriptional Enhancer in a Mouse Amyloid Gene
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The Structure and Function of the Mouse Hepatocyte Stimulating Factora
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Prothrombin Expression in the Adult and Fetal Rabbit Liver
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“IL-6 is an major inducer of this protein [34].”
BackgroundTranscriptionally Active Haptoglobin-Related (Hpr) Gene in Hepatoma G 2 and Leukemia Molt-4 Cells
Tabak, S., Lev, A., Valansi, C., Aker, Ö. E., & Shalitin, C. (1996) · DNA and Cell Biology · doi:10.1089/dna.1996.15.1001 · Cited by 8 · see citing works
“Nuclear run-on experiments have shown that Hpr is not transcribed in either fetal or adult liver, although it does not have any of the features commonly associated with pseudogenes (Oliviero et al., 1987; Bensi ef al, 1985).”
Influential
- Authors
- Oliviero, S., Morrone, G., & Cortese, R.
- Affiliations
- European Molecular Biology Laboratory (DE)
- Venue
- The EMBO Journal
- Published
- 1987-07-01
- Volume
- 6
- Issue
- 7
- Pages
- 1905-1912
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC553575
- OpenAlex
- W408517226
- Cited by
- 123
- References
- 33
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 2 · 2015: 3 · 2014: 2 · 2012: 1
- FWCI
- 8.83
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Use Siena air (University of Siena) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- transcriptional regulation, acute phase response, fetal liver, hepatoma cell lines, HepG2 cells, Hep3B cells, 5'-flanking region, cell type-specific gene expression, chloramphenicol acetyltransferase reporter, developmental gene expression
- MeSH terms
- Adult, Base Sequence, Cell Line, Cloning, Molecular, Fetus, Gene Expression Regulation, Genes, Haptoglobins, HeLa Cells, Carcinoma, Hepatocellular, Humans, Liver, Liver Neoplasms, Molecular Sequence Data, Plasmids, Transcription, Genetic
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