The Nuclear Localization Signal of NF-κB p50 Enters the Cells via Syndecan-Mediated Endocytosis and Inhibits NF-κB Activity
It is well established that cationic peptides can enter cells following attachment to polyanionic membrane components. We report that the basic nuclear localization signal (NLS) of the NF-κB p50 subunit is internalized via lipid raft-dependent endocytosis mediated by heparan sulfate proteoglycans an...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2023
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| Sorozat: | INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS
29 No. 5 |
| Tárgyszavak: | |
| doi: | 10.1007/s10989-023-10548-9 |
| mtmt: | 34050718 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/27832 |
| LEADER | 03037nab a2200301 i 4500 | ||
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| 001 | publ27832 | ||
| 005 | 20230710101944.0 | ||
| 008 | 230710s2023 hu o 0|| Angol d | ||
| 022 | |a 1573-3149 | ||
| 024 | 7 | |a 10.1007/s10989-023-10548-9 |2 doi | |
| 024 | 7 | |a 34050718 |2 mtmt | |
| 040 | |a SZTE Publicatio Repozitórium |b hun | ||
| 041 | |a Angol | ||
| 100 | 1 | |a Letoha Annamária | |
| 245 | 1 | 4 | |a The Nuclear Localization Signal of NF-κB p50 Enters the Cells via Syndecan-Mediated Endocytosis and Inhibits NF-κB Activity |h [elektronikus dokumentum] / |c Letoha Annamária |
| 260 | |c 2023 | ||
| 300 | |a 16 | ||
| 490 | 0 | |a INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS |v 29 No. 5 | |
| 520 | 3 | |a It is well established that cationic peptides can enter cells following attachment to polyanionic membrane components. We report that the basic nuclear localization signal (NLS) of the NF-κB p50 subunit is internalized via lipid raft-dependent endocytosis mediated by heparan sulfate proteoglycans and exerts significant NF-κB inhibitory activities both in vitro and in vivo. In vitro uptake experiments revealed that the p50 NLS peptide (CYVQRKRQKLMP) enters the cytoplasm and accumulates in the nucleus at 37 °C. Depleting cellular ATP pools or decreasing temperature to 4 °C abolished peptide internalization, confirming the active, energy-dependent endocytic uptake. Co-incubation with heparan sulfate or replacing the peptide’s basic residues with glycines markedly reduced the intracellular entry of the p50 NLS, referring to the role of polyanionic cell-surface proteoglycans in internalization. Furthermore, treatment with methyl-β-cyclodextrin greatly inhibited the peptide’s membrane translocation. Overexpression of the isoforms of the syndecan family of transmembrane proteoglycans, especially syndecan-4, increased the cellular internalization of the NLS, suggesting syndecans’ involvement in the peptide’s cellular uptake. In vitro , p50 NLS reduced NF-κB activity in TNF-α-induced L929 fibroblasts and LPS-stimulated RAW 264.7 macrophages. TNF-α-induced ICAM-1 expression of HMEC-1 human endothelial cells could also be inhibited by the peptide. Fifteen minutes after its intraperitoneal injection, the peptide rapidly entered the cells of the pancreas, an organ with marked syndecan-4 expression. In an acute pancreatitis model, an inflammatory disorder triggered by the activation of stress-responsive transcription factors like NF-κB, administration of the p50 NLS peptide reduced the severity of pancreatic inflammation by blocking NF-κB transcription activity and ameliorating the examined laboratory and histological markers of pancreatitis. | |
| 650 | 4 | |a Kémiai tudományok | |
| 650 | 4 | |a Általános orvostudomány | |
| 700 | 0 | 1 | |a Hudák Anett |e aut |
| 700 | 0 | 1 | |a Bozsó Zsolt |e aut |
| 700 | 0 | 1 | |a Vizler Csaba |e aut |
| 700 | 0 | 1 | |a Veres Gábor |e aut |
| 700 | 0 | 1 | |a Szilák László |e aut |
| 700 | 0 | 1 | |a Letoha Tamás |e aut |
| 856 | 4 | 0 | |u http://publicatio.bibl.u-szeged.hu/27832/1/Letoha.pdf |z Dokumentum-elérés |