Anti-inflammatory Effect of a Cell-Penetrating Peptide Targeting the Nrf2/Keap1 Interaction
Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is increasingly recognized as a central regulator of multiple signaling pathways in inflammation and cancer, and the ability to use chemical biological tools to investigate its biological effects is very attractive. A peptide comprising a TAT-conjug...
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| Published in | ACS medicinal chemistry letters Vol. 3; no. 5; pp. 407 - 410 |
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| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
American Chemical Society
10.05.2012
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1948-5875 1948-5875 |
| DOI | 10.1021/ml300041g |
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| Abstract | Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is increasingly recognized as a central regulator of multiple signaling pathways in inflammation and cancer, and the ability to use chemical biological tools to investigate its biological effects is very attractive. A peptide comprising a TAT-conjugated Nrf2 sequence is shown to activate Nrf2 and its downstream target gene heme-oxygenase-1 (HO-1) in a dose-dependent manner in intact human THP-1 monocytes. Levels of Nrf2 protein peak after 3 h, whereas HO-1 mRNA and protein peak after 6 and 12 h, respectively. The peptide is also shown to inhibit the production of the pro-inflammatory cytokine TNF. The TAT-14mer constitutes a useful chemical biology tool with potential therapeutic applications. |
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| AbstractList | Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is increasingly recognized as a central regulator of multiple signaling pathways in inflammation and cancer, and the ability to use chemical biological tools to investigate its biological effects is very attractive. A peptide comprising a TAT-conjugated Nrf2 sequence is shown to activate Nrf2 and its downstream target gene heme-oxygenase-1 (HO-1) in a dose-dependent manner in intact human THP-1 monocytes. Levels of Nrf2 protein peak after 3 h, whereas HO-1 mRNA and protein peak after 6 and 12 h, respectively. The peptide is also shown to inhibit the production of the pro-inflammatory cytokine TNF. The TAT-14mer constitutes a useful chemical biology tool with potential therapeutic applications.Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is increasingly recognized as a central regulator of multiple signaling pathways in inflammation and cancer, and the ability to use chemical biological tools to investigate its biological effects is very attractive. A peptide comprising a TAT-conjugated Nrf2 sequence is shown to activate Nrf2 and its downstream target gene heme-oxygenase-1 (HO-1) in a dose-dependent manner in intact human THP-1 monocytes. Levels of Nrf2 protein peak after 3 h, whereas HO-1 mRNA and protein peak after 6 and 12 h, respectively. The peptide is also shown to inhibit the production of the pro-inflammatory cytokine TNF. The TAT-14mer constitutes a useful chemical biology tool with potential therapeutic applications. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is increasingly recognized as a central regulator of multiple signaling pathways in inflammation and cancer, and the ability to use chemical biological tools to investigate its biological effects is very attractive. A peptide comprising a TAT-conjugated Nrf2 sequence is shown to activate Nrf2 and its downstream target gene heme-oxygenase-1 (HO-1) in a dose-dependent manner in intact human THP-1 monocytes. Levels of Nrf2 protein peak after 3 h, whereas HO-1 mRNA and protein peak after 6 and 12 h, respectively. The peptide is also shown to inhibit the production of the pro-inflammatory cytokine TNF. The TAT-14mer constitutes a useful chemical biology tool with potential therapeutic applications. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is increasingly recognized as a central regulator of multiple signaling pathways in inflammation and cancer, and the ability to use chemical biological tools to investigate its biological effects is very attractive. A peptide comprising a TAT-conjugated Nrf2 sequence is shown to activate Nrf2 and its downstream target gene heme-oxygenase-1 (HO-1) in a dose-dependent manner in intact human THP-1 monocytes. Levels of Nrf2 protein peak after 3 h, whereas HO-1 mRNA and protein peak after 6 and 12 h, respectively. The peptide is also shown to inhibit the production of the pro-inflammatory cytokine TNF. The TAT-14mer constitutes a useful chemical biology tool with potential therapeutic applications. |
| Author | O'Connell, Maria A Cowan, Jonathan Payerne, Estelle Steel, Richard Searcey, Mark |
| AuthorAffiliation | University of East Anglia |
| AuthorAffiliation_xml | – name: University of East Anglia |
| Author_xml | – sequence: 1 givenname: Richard surname: Steel fullname: Steel, Richard – sequence: 2 givenname: Jonathan surname: Cowan fullname: Cowan, Jonathan – sequence: 3 givenname: Estelle surname: Payerne fullname: Payerne, Estelle – sequence: 4 givenname: Maria A surname: O'Connell fullname: O'Connell, Maria A email: m.oconnell@uea.ac.uk, m.searcey@uea.ac.uk – sequence: 5 givenname: Mark surname: Searcey fullname: Searcey, Mark email: m.oconnell@uea.ac.uk, m.searcey@uea.ac.uk |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/22582137$$D View this record in MEDLINE/PubMed |
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| Keywords | Nrf2 Keap-1 inflammation cell-penetrating peptide protein−protein interaction antioxidant response |
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| Title | Anti-inflammatory Effect of a Cell-Penetrating Peptide Targeting the Nrf2/Keap1 Interaction |
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