Regulation of the CD36 scavenger receptor by the antioxidant 7,8-dihydroneopterin.
| dc.contributor.author | Yeandle, Anthony | |
| dc.date.accessioned | 2017-08-10T21:07:20Z | |
| dc.date.available | 2017-08-10T21:07:20Z | |
| dc.date.issued | 2017 | en |
| dc.description.abstract | OxLDL uptake via the CD36 scavenger receptor leads to foam cell formation and is at the core of the development of atherosclerosis. One potential protective mechanism against this process involves the human macrophage derived anti-oxidant 7,8-dihydroneopterin (7,8-NP) down regulating CD36. This study characterised CD36 down regulation in the U937 monocyte-like cell line, and examined a mechanism of action involving MAP kinase mediated control of the PPARγ transcription factor. Western blot analysis showed that in U937 cells 7,8-NP concentrations up to 150μM down regulated CD36 to ~40% of basal levels over 24 hours. The effect seen here was stronger than that previously observed with human monocyte derived macrophages (HMDM). The oxidised product of 7,8-NP, neopterin, had no significant effect. CD36 levels were able to recover after down regulation and neared control levels 24 hours after 7,8-NP removal. CD36 protein levels were found to be under control of PPARγ and it was shown that 7,8-NP likely only has its effect at the transcriptional level, and did not enhance the proteolytic removal of CD36. PPARγ contains a MAP kinase binding site which when phosphorylated prevents the transcription of CD36. Co-incubation of selective MAP kinase inhibitors SP600125 (JNK) and PD98059 (ERK1/2) with 7,8-NP failed to block CD36 down regulation. The effect of p38 and NF-κB signalling in CD36 down regulation was additionally explored using their inhibitors (SB202190 and BAY 11-7082 respectively), but likewise did not block 7,8-NP’s effect. The results confirm that in the U937 cell line 7,8-NP can decrease the levels of CD36, and that a regulatory pathway involving PPARγ is likely. It is also shown that 7,8-NPs mechanism of action does not involve the activation of a MAP kinase cascade phosphorylating PPARγ. This points towards a different mechanism of action, possibly involving PPARγ’s lipid ligand binding site. | en |
| dc.identifier.uri | http://hdl.handle.net/10092/13797 | |
| dc.identifier.uri | http://dx.doi.org/10.26021/7951 | |
| dc.language | English | |
| dc.language.iso | en | |
| dc.publisher | University of Canterbury | en |
| dc.rights | All Rights Reserved | en |
| dc.rights.uri | https://canterbury.libguides.com/rights/theses | en |
| dc.title | Regulation of the CD36 scavenger receptor by the antioxidant 7,8-dihydroneopterin. | en |
| dc.type | Theses / Dissertations | en |
| thesis.degree.discipline | Biochemistry | en |
| thesis.degree.grantor | University of Canterbury | en |
| thesis.degree.level | Masters | en |
| thesis.degree.name | Master of Science | en |
| uc.bibnumber | 2502298 | |
| uc.college | Faculty of Science | en |