repository
Signaling pathways mediated by Toll-like Receptor 2 involved in the protection of oligodendrocytes from ischaemic cell death
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.advisor | Byung Gon Kim | - |
| dc.contributor.author | CHOWDHURY, SAMMA TASNEEM | - |
| dc.date.accessioned | 2019-10-21T07:30:27Z | - |
| dc.date.available | 2019-10-21T07:30:27Z | - |
| dc.date.issued | 2017-08 | - |
| dc.identifier.other | 25815 | - |
| dc.identifier.uri | https://dspace.ajou.ac.kr/handle/2018.oak/19064 | - |
| dc.description | 학위논문(석사)--아주대학교 일반대학원 :의생명과학과,2017. 8 | - |
| dc.description.tableofcontents | I. INTRODUCTION 1 A. Importance of ischaemic white matter stroke research 1 B. Pathophysiology of ischaemic white matter stroke 2 C. Myelination and oligodendrocyte 2 D. Toll-like Receptor 2 and OLs 3 E. Signaling pathways 4 F. Aims of the thesis research 7 II. MATERIALS AND METHODS 8 1. Primary OL culture 8 2. Collection of oligodendrocyte precursor cells (OPCs) 8 3. Oxygen-glucose deprivation (OGD) challenge 9 4. Western blot 9 5. Inhibitor treatment 10 6. siRNA nucleofaction 10 7. Cell viability assay 10 8. Cytotoxicity assay/LDH assay 11 9. Statistical analysis 11 III. RESULTS 12 1. PAM3 activates intracellular signaling pathways 12 2. Further activation of intracellular signaling pathways after OGD 14 3. in vitro PAM3 mediated cell survival 16 4. p38 MAPK and NFκB inhibition reverse the effect of PAM3 on ischaemic cell 18 5. Genetic knockdown of p38 MAPK and NFκB attenuates PAM3 mediated prosurvival effects on OLs under ischaemic stress 23 IV. DISCUSSION 28 V. CONCLUSION 31 VI. REFERENCES 32 | - |
| dc.language.iso | eng | - |
| dc.publisher | The Graduate School, Ajou University | - |
| dc.rights | 아주대학교 논문은 저작권에 의해 보호받습니다. | - |
| dc.title | Signaling pathways mediated by Toll-like Receptor 2 involved in the protection of oligodendrocytes from ischaemic cell death | - |
| dc.title.alternative | Signaling pathways mediated by Toll-like Receptor 2 involved in the protection of oligodendrocytes from ischaemic cell death | - |
| dc.type | Thesis | - |
| dc.contributor.affiliation | 아주대학교 일반대학원 | - |
| dc.contributor.alternativeName | CHOWDHURY SAMMA TASNEEM | - |
| dc.contributor.department | 일반대학원 의생명과학과 | - |
| dc.date.awarded | 2017. 8 | - |
| dc.description.degree | Master | - |
| dc.identifier.localId | 788523 | - |
| dc.identifier.url | http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000025815 | - |
| dc.subject.keyword | neuroscience | - |
| dc.description.alternativeAbstract | Oligodendrocytes (OLs), myelinating glia of central nervous system, extend multiple branches to ensheath axons. Rapid saltatory conduction of nerve impulse depends on myelin sheath. Furthermore, recent studies have shown that axonal integrity cannot be maintained without intact myelin sheath. Therefore, devastating neurological deficits occurs when ischaemic white matter injury causes demyelination and OL loss. Treating OL loss and demyelination can be a therapeutic target for ischaemic white matter stroke. Previously, we found that Toll-like receptor 2 (TLR2) expressed in OLs provide cell-autonomous protective effects on ischaemic cell death. Here, I sought to identify the intracellular signaling pathways downstream of TLR2 that are involved in the protection of OLs from ischaemic cell death. Several protective pathways such as p38 MAP kinase, CREB, NFκB, AKT, and ERK can be activated in response of cellular stresses and participate in cytoprotective effects. Treatment of PAM3CSK4 (PAM3), a well-known TLR2 agonist, induced phosphorylation of these pathways except AKT. The same pathways were activated in response to PAM3 treatment following oxygen glucose deprivation (OGD). To identify a specific pathway causally linked to the PAM3-mediated promotion of OL survival, each pathway was inhibited pharmacologically or genetically using specific inhibitors or siRNA, respectively, and the extent of OL death was measured after using CCK or LDH assay. Among all the tested, pathways p38 MAPK inhibitor and NFκB inhibitor significantly attenuated the pro-survival effect of PAM3. siRNA knockdown experiments confirmed functional implication of the two pathways in the PAM3-mediated increase of OL survival. These results demonstrated that TLR2 provides protective effects on OLs under ischaemic stress through the p38 MAPK and NFκB pathways. Further studies will clarify effector molecules downstream of the two pathways that confer cellular protection on ischaemic OLs. | - |
- Appears in Collections:
- Graduate School of Ajou University > Department of Biomedical Sciences > 3. Theses(Master)
- Files in This Item:
- There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.
-
- License
- STATISTICS
- Total Visit :3,735,950
- Total Download :1,818
- Today View :13,608
