Intracellular Protein S-Nitrosylation—A Cells Response to Extracellular S100B and RAGE Receptor
Human S100B is a small, multifunctional protein. Its activity, inside and outside cells, contributes to the biology of the brain, muscle, skin, and adipocyte tissues. Overexpression of S100B occurs in Down Syndrome, Alzheimer’s disease, Creutzfeldt–Jakob disease, schizophrenia, multiple sclerosis, b...
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| Format: | Article |
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MDPI AG
2022-04-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/5/613 |
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| author | Monika Zaręba-Kozioł Michał Burdukiewicz Aleksandra Wysłouch-Cieszyńska |
| author_facet | Monika Zaręba-Kozioł Michał Burdukiewicz Aleksandra Wysłouch-Cieszyńska |
| author_sort | Monika Zaręba-Kozioł |
| collection | DOAJ |
| description | Human S100B is a small, multifunctional protein. Its activity, inside and outside cells, contributes to the biology of the brain, muscle, skin, and adipocyte tissues. Overexpression of S100B occurs in Down Syndrome, Alzheimer’s disease, Creutzfeldt–Jakob disease, schizophrenia, multiple sclerosis, brain tumors, epilepsy, melanoma, myocardial infarction, muscle disorders, and sarcopenia. Modulating the activities of S100B, related to human diseases, without disturbing its physiological functions, is vital for drug and therapy design. This work focuses on the extracellular activity of S100B and one of its receptors, the Receptor for Advanced Glycation End products (RAGE). The functional outcome of extracellular S100B, partially, depends on the activation of intracellular signaling pathways. Here, we used Biotin Switch Technique enrichment and mass-spectrometry-based proteomics to show that the appearance of the S100B protein in the extracellular milieu of the mammalian Chinese Hamster Ovary (CHO) cells, and expression of the membrane-bound RAGE receptor, lead to changes in the intracellular S-nitrosylation of, at least, more than a hundred proteins. Treatment of the wild-type CHO cells with nanomolar or micromolar concentrations of extracellular S100B modulates the sets of S-nitrosylation targets inside cells. The cellular S-nitrosome is tuned differently, depending on the presence or absence of stable RAGE receptor expression. The presented results are a proof-of-concept study, suggesting that S-nitrosylation, like other post-translational modifications, should be considered in future research, and in developing tailored therapies for S100B and RAGE receptor-related diseases. |
| first_indexed | 2024-03-10T03:16:39Z |
| format | Article |
| id | doaj.art-91d88f20edbd44f1b331e513b3c143a2 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T03:16:39Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-91d88f20edbd44f1b331e513b3c143a22023-11-23T10:12:58ZengMDPI AGBiomolecules2218-273X2022-04-0112561310.3390/biom12050613Intracellular Protein S-Nitrosylation—A Cells Response to Extracellular S100B and RAGE ReceptorMonika Zaręba-Kozioł0Michał Burdukiewicz1Aleksandra Wysłouch-Cieszyńska2Mass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, PolandClinical Research Centre, Medical University of Białystok, Kilińskiego 1, 15-369 Białystok, PolandMass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, PolandHuman S100B is a small, multifunctional protein. Its activity, inside and outside cells, contributes to the biology of the brain, muscle, skin, and adipocyte tissues. Overexpression of S100B occurs in Down Syndrome, Alzheimer’s disease, Creutzfeldt–Jakob disease, schizophrenia, multiple sclerosis, brain tumors, epilepsy, melanoma, myocardial infarction, muscle disorders, and sarcopenia. Modulating the activities of S100B, related to human diseases, without disturbing its physiological functions, is vital for drug and therapy design. This work focuses on the extracellular activity of S100B and one of its receptors, the Receptor for Advanced Glycation End products (RAGE). The functional outcome of extracellular S100B, partially, depends on the activation of intracellular signaling pathways. Here, we used Biotin Switch Technique enrichment and mass-spectrometry-based proteomics to show that the appearance of the S100B protein in the extracellular milieu of the mammalian Chinese Hamster Ovary (CHO) cells, and expression of the membrane-bound RAGE receptor, lead to changes in the intracellular S-nitrosylation of, at least, more than a hundred proteins. Treatment of the wild-type CHO cells with nanomolar or micromolar concentrations of extracellular S100B modulates the sets of S-nitrosylation targets inside cells. The cellular S-nitrosome is tuned differently, depending on the presence or absence of stable RAGE receptor expression. The presented results are a proof-of-concept study, suggesting that S-nitrosylation, like other post-translational modifications, should be considered in future research, and in developing tailored therapies for S100B and RAGE receptor-related diseases.https://www.mdpi.com/2218-273X/12/5/613extracellular S100Breceptor RAGES-nitrosomeSNOSIDmass spectrometry |
| spellingShingle | Monika Zaręba-Kozioł Michał Burdukiewicz Aleksandra Wysłouch-Cieszyńska Intracellular Protein S-Nitrosylation—A Cells Response to Extracellular S100B and RAGE Receptor Biomolecules extracellular S100B receptor RAGE S-nitrosome SNOSID mass spectrometry |
| title | Intracellular Protein S-Nitrosylation—A Cells Response to Extracellular S100B and RAGE Receptor |
| title_full | Intracellular Protein S-Nitrosylation—A Cells Response to Extracellular S100B and RAGE Receptor |
| title_fullStr | Intracellular Protein S-Nitrosylation—A Cells Response to Extracellular S100B and RAGE Receptor |
| title_full_unstemmed | Intracellular Protein S-Nitrosylation—A Cells Response to Extracellular S100B and RAGE Receptor |
| title_short | Intracellular Protein S-Nitrosylation—A Cells Response to Extracellular S100B and RAGE Receptor |
| title_sort | intracellular protein s nitrosylation a cells response to extracellular s100b and rage receptor |
| topic | extracellular S100B receptor RAGE S-nitrosome SNOSID mass spectrometry |
| url | https://www.mdpi.com/2218-273X/12/5/613 |
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