Contribution of O-GlcNAc modification of NF-κB p65 in the attenuation of diabetes-induced haptoglobin expression in rat liver
Haptoglobin (Hp) is a hemoglobin-binding protein that prevents free hemoglobin-induced tissue oxidative damage. In streptozotocin-induced diabetic rats, the initial elevation of Hp expression in the serum and liver tends to decrease with diabetes progression, contributing to increased oxidative stre...
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| Format: | Article |
| Language: | English |
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University of Belgrade, University of Novi Sad
2020-01-01
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| Series: | Archives of Biological Sciences |
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| Online Access: | http://www.doiserbia.nb.rs/img/doi/0354-4664/2020/0354-46642000049M.pdf |
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| author | Martinović Vesna I. Arambašić-Jovanović Jelena D. Bogojević Desanka B. Ivanović Anđelija S. Otašević Vesna M. Stančić Ana T. Grigorov Ilijana I. |
| author_facet | Martinović Vesna I. Arambašić-Jovanović Jelena D. Bogojević Desanka B. Ivanović Anđelija S. Otašević Vesna M. Stančić Ana T. Grigorov Ilijana I. |
| author_sort | Martinović Vesna I. |
| collection | DOAJ |
| description | Haptoglobin (Hp) is a hemoglobin-binding protein that prevents free hemoglobin-induced tissue oxidative damage. In streptozotocin-induced diabetic rats, the initial elevation of Hp expression in the serum and liver tends to decrease with diabetes progression, contributing to increased oxidative stress. Glucose toxicity and diabetic complications are closely related to increased modification of nucleocytoplasmic proteins by O-linked-N-acetylglucosamine (O-GlcNAc). We examined the contribution of O-GlcNAcylation of NF-κB p65 to changes in liver Hp expression in diabetic rats. WGA-affinity chromatography revealed a progressive increase in O-GlcNAcylation in nuclear NF-κB p65 during eight weeks of diabetes. DNA-affinity chromatography followed by immunoblot analysis revealed that decreased Hp expression at 4 and 8 weeks of diabetes was accompanied by the absence of Hp gene hormone-responsive element (HRE) occupancy with NF-κB p65, low occupancy with glucocorticoid receptor (GR), and almost no changes in STAT3 occupancy compared to 2 weeks, when Hp expression was highest. Coimmunoprecipitation experiments indicate that these events were the result of impaired NF-κB p65/STAT3 and GR/STAT3 interactions. Results suggest that the attenuation of Hp expression associated with diabetes was at least in part the result of O-GlcNAcylation of NF-κB p65, which prevents the formation of an effective transcription initiation complex on the Hp gene promoter. |
| first_indexed | 2024-12-16T10:01:27Z |
| format | Article |
| id | doaj.art-d5410168f2d94d45b10fdd23a4148865 |
| institution | Directory Open Access Journal |
| issn | 0354-4664 1821-4339 |
| language | English |
| last_indexed | 2024-12-16T10:01:27Z |
| publishDate | 2020-01-01 |
| publisher | University of Belgrade, University of Novi Sad |
| record_format | Article |
| series | Archives of Biological Sciences |
| spelling | doaj.art-d5410168f2d94d45b10fdd23a41488652022-12-21T22:35:47ZengUniversity of Belgrade, University of Novi SadArchives of Biological Sciences0354-46641821-43392020-01-0172455556510.2298/ABS200928049M0354-46642000049MContribution of O-GlcNAc modification of NF-κB p65 in the attenuation of diabetes-induced haptoglobin expression in rat liverMartinović Vesna I.0Arambašić-Jovanović Jelena D.1Bogojević Desanka B.2Ivanović Anđelija S.3Otašević Vesna M.4Stančić Ana T.5Grigorov Ilijana I.6Department of Molecular Biology, Institute for Biological Research “Siniša Stanković”, National Institute of the Republic of Serbia, University of Belgrade, Belgrade, SerbiaDepartment of Molecular Biology, Institute for Biological Research “Siniša Stanković”, National Institute of the Republic of Serbia, University of Belgrade, Belgrade, SerbiaDepartment of Molecular Biology, Institute for Biological Research “Siniša Stanković”, National Institute of the Republic of Serbia, University of Belgrade, Belgrade, SerbiaDepartment of Molecular Biology, Institute for Biological Research “Siniša Stanković”, National Institute of the Republic of Serbia, University of Belgrade, Belgrade, SerbiaDepartment of Molecular Biology, Institute for Biological Research “Siniša Stanković”, National Institute of the Republic of Serbia, University of Belgrade, Belgrade, SerbiaDepartment of Molecular Biology, Institute for Biological Research “Siniša Stanković”, National Institute of the Republic of Serbia, University of Belgrade, Belgrade, SerbiaDepartment of Molecular Biology, Institute for Biological Research “Siniša Stanković”, National Institute of the Republic of Serbia, University of Belgrade, Belgrade, SerbiaHaptoglobin (Hp) is a hemoglobin-binding protein that prevents free hemoglobin-induced tissue oxidative damage. In streptozotocin-induced diabetic rats, the initial elevation of Hp expression in the serum and liver tends to decrease with diabetes progression, contributing to increased oxidative stress. Glucose toxicity and diabetic complications are closely related to increased modification of nucleocytoplasmic proteins by O-linked-N-acetylglucosamine (O-GlcNAc). We examined the contribution of O-GlcNAcylation of NF-κB p65 to changes in liver Hp expression in diabetic rats. WGA-affinity chromatography revealed a progressive increase in O-GlcNAcylation in nuclear NF-κB p65 during eight weeks of diabetes. DNA-affinity chromatography followed by immunoblot analysis revealed that decreased Hp expression at 4 and 8 weeks of diabetes was accompanied by the absence of Hp gene hormone-responsive element (HRE) occupancy with NF-κB p65, low occupancy with glucocorticoid receptor (GR), and almost no changes in STAT3 occupancy compared to 2 weeks, when Hp expression was highest. Coimmunoprecipitation experiments indicate that these events were the result of impaired NF-κB p65/STAT3 and GR/STAT3 interactions. Results suggest that the attenuation of Hp expression associated with diabetes was at least in part the result of O-GlcNAcylation of NF-κB p65, which prevents the formation of an effective transcription initiation complex on the Hp gene promoter.http://www.doiserbia.nb.rs/img/doi/0354-4664/2020/0354-46642000049M.pdfhaptoglobingene expressiondiabetesnf-kb p65o-linked-n-acetylglucosamine modification |
| spellingShingle | Martinović Vesna I. Arambašić-Jovanović Jelena D. Bogojević Desanka B. Ivanović Anđelija S. Otašević Vesna M. Stančić Ana T. Grigorov Ilijana I. Contribution of O-GlcNAc modification of NF-κB p65 in the attenuation of diabetes-induced haptoglobin expression in rat liver Archives of Biological Sciences haptoglobin gene expression diabetes nf-kb p65 o-linked-n-acetylglucosamine modification |
| title | Contribution of O-GlcNAc modification of NF-κB p65 in the attenuation of diabetes-induced haptoglobin expression in rat liver |
| title_full | Contribution of O-GlcNAc modification of NF-κB p65 in the attenuation of diabetes-induced haptoglobin expression in rat liver |
| title_fullStr | Contribution of O-GlcNAc modification of NF-κB p65 in the attenuation of diabetes-induced haptoglobin expression in rat liver |
| title_full_unstemmed | Contribution of O-GlcNAc modification of NF-κB p65 in the attenuation of diabetes-induced haptoglobin expression in rat liver |
| title_short | Contribution of O-GlcNAc modification of NF-κB p65 in the attenuation of diabetes-induced haptoglobin expression in rat liver |
| title_sort | contribution of o glcnac modification of nf κb p65 in the attenuation of diabetes induced haptoglobin expression in rat liver |
| topic | haptoglobin gene expression diabetes nf-kb p65 o-linked-n-acetylglucosamine modification |
| url | http://www.doiserbia.nb.rs/img/doi/0354-4664/2020/0354-46642000049M.pdf |
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