Full Text Available
Note: Clicking the button above will open the full text document at the original institutional repository in a new window.
Anti-inflammatory properties of peptides derived from the carboxy-terminal region of a defensin from the tick Ornithodoros savignyi
Dissertation (MSc)--University of Pretoria, 2015.
Saved in:
| Other Authors: | |
|---|---|
| Format: | Thesis |
| Language: | English |
| Published: |
University of Pretoria
2015
|
| Subjects: | |
| Tags: |
No Tags, Be the first to tag this record!
|
| _version_ | 1867613561163874304 |
|---|---|
| access_status_str | Open Access |
| author2 | Gaspar, A.R.M. (Anabella Regina Marques) |
| author_browse | Gaspar, A.R.M. (Anabella Regina Marques) |
| author_facet | Gaspar, A.R.M. (Anabella Regina Marques) |
| collection | Thesis |
| dc_rights_str_mv | © 2015 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. |
| description | Dissertation (MSc)--University of Pretoria, 2015. |
| format | Thesis |
| id | oai:repository.up.ac.za:2263/50671 |
| institution | University of Pretoria (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:38:05.905Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository |
| publishDate | 2015 |
| publishDateRange | 2015 |
| publishDateSort | 2015 |
| publisher | University of Pretoria |
| publisherStr | University of Pretoria |
| record_format | dspace |
| source_str | UPSpace — University of Pretoria Institutional Repository |
| spelling | oai:repository.up.ac.za:2263/50671 Anti-inflammatory properties of peptides derived from the carboxy-terminal region of a defensin from the tick Ornithodoros savignyi Gaspar, A.R.M. (Anabella Regina Marques) dette.x@gmail.com Neitz, A.W.H. (Albert Walter Herman) Malan, Melissa UCTD Dissertation (MSc)--University of Pretoria, 2015. Lipopolysaccharides (LPS), when released from the outer membrane of Gram-negative bacteria, bind to macrophages, inducing production of pro-inflammatory cytokines and mediator molecules. In addition, associated overproduction of free radicals causes oxidative stress and is a major factor for triggering local inflammation causing tissue and cellular damage. Several cationic antimicrobial peptides (AMPs), besides antimicrobial activity, also possess anti-inflammatory and antioxidant properties. The advantage of this multifunctionality is that while the infection is cleared, inflammation and associated free radical cellular and tissue damage is reduced. In this study the potential anti-inflammatory and antioxidant properties of synthetic AMPs, Os and Os-C, derived from a defensin (OsDef2) previously identified in the tick, Ornithodoros savignyi, were investigated. Os is derived from the carboxy-terminal of OsDef2, whereas Os-C is an analogue of Os from which the Cys residues were omitted. Both Os and Os-C were found to bind LPS in vitro by measuring their ability to inhibit the LPS-induced activation of Limulus amoebocyte lysate (LAL) enzyme. The binding of free LPS caused the loss of both Os and Os-C bactericidal activity against Escherichia coli (E.coli) confirming the affinity of both peptides for LPS. Like glutathione (GSH), Os scavenged nitric oxide (NO), which is possibly due to the presence of three Cys residues and the formation of nitrosothiols with NO. Melittin (control) and Os-C, peptides lacking Cys residues, were found to be poor NO scavengers. RAW 264.7 cells exposed simultaneously to LPS/IFN-γ and Os or Os-C showed that both peptides attenuated the LPS-induced production of NO, as well as TNF-α, in a dosage-dependant manner. In contrast, a 90 minute pre-incubation of RAW 264.7 cells with peptides, followed by LPS/IFN-γ stimulation, showed that both peptides, had a lesser effect on the inhibition of NO production when compared to controls. Although the control peptides, melittin and polymyxin B, had higher NO inhibition activity, both were associated with a loss of cellular viability. The results of the pre-incubation experiments indicated that Os and Os-C, besides binding to LPS, might have specific intracellular sites of action that allow for inhibition of LPS mediated NO formation. In contrast to both melittin and polymyxin B, Os and Os-C were found to be non-toxic towards the RAW 264.7 cells even at peptide concentrations 132 and 57 times higher than the minimum bactericidal concentration (MBC), respectively. Os was found to possess higher cellular antioxidant activity compared to Os-C, which may be attributed to the presence of antioxidant amino acids. This study identifies the multifunctional properties of Os and Os-C, however the specific mode of action of each peptide needs to be further elucidated. tm2015 Biochemistry MSc Unrestricted 2015-11-25T09:47:10Z 2015-11-25T09:47:10Z 2015/09/01 2015 Dissertation Malan, M 2015, Anti-inflammatory properties of peptides derived from the carboxy-terminal region of a defensin from the tick Ornithodoros savignyi, MSc Dissertation, University of Pretoria, Pretoria, viewed yymmdd <http://hdl.handle.net/2263/50671> S2015 http://hdl.handle.net/2263/50671 en © 2015 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. application/pdf University of Pretoria |
| spellingShingle | UCTD Anti-inflammatory properties of peptides derived from the carboxy-terminal region of a defensin from the tick Ornithodoros savignyi |
| title | Anti-inflammatory properties of peptides derived from the carboxy-terminal region of a defensin from the tick Ornithodoros savignyi |
| title_full | Anti-inflammatory properties of peptides derived from the carboxy-terminal region of a defensin from the tick Ornithodoros savignyi |
| title_fullStr | Anti-inflammatory properties of peptides derived from the carboxy-terminal region of a defensin from the tick Ornithodoros savignyi |
| title_full_unstemmed | Anti-inflammatory properties of peptides derived from the carboxy-terminal region of a defensin from the tick Ornithodoros savignyi |
| title_short | Anti-inflammatory properties of peptides derived from the carboxy-terminal region of a defensin from the tick Ornithodoros savignyi |
| title_sort | anti inflammatory properties of peptides derived from the carboxy terminal region of a defensin from the tick ornithodoros savignyi |
| topic | UCTD |
| url | http://hdl.handle.net/2263/50671 |