E-resources
-
Orhan, İlkcan Ercan
01/2023Dissertation
Despite contemporary improvements in neonatal care, bilirubin-induced neurological dysfunction (BIND), which is caused by hyperbilirubinemia, continues to be a major cause of death or permanent disability in the developing world. Inflammationis thought to be one of the main causes of brain damage after bilirubin exposure, eventhough the precise mechanism is still unknown. This project aims to investigate the effect of bilirubin in inflammasome activation and pyroptotic cell death in in vitro and in vivo examinations and to decide if the inflammasome activation depends on NOD-Like Receptor 3 (NLRP3. 50 µM bilirubin administration in N9 microglia cell line results in inflammasome activation assessed by increased IL-1β cytokine, IL-1β, NLRP3 mRNA expression and caspase-1 (p20), IL-1β and NLRP3 protein level. The relation betweenbilirubin-related inflammasome activation leading to microglial cell death was successfully determined by propidium iodide staining. Whether inflammasome activation and cell death are mediated via the NLRP3 pathway was confirmed by functional assays with NLRP3 siRNA inhibition. Following injection of bilirubin into the cisterna magna of a neonatal mouse, activation of the NLRP3 inflammasome was determined by elevated IL-1β, NLRP3 mRNA, and protein level and caspase-1(p20) protein secretion in wild-type animals. On the contrary, bilirubin injected NLRP3 knock-out (Nlrp3-/-) and caspase-1 knock-out (Caspase-1 -/-)mice has not released active caspase-1 or IL-1β. All of these findings suggest that bilirubin plays a part in the activation of the inflammasome in the brain and that NLRP3 is essential for this activation. With the identification of underlying molecular pathways, additional researchon the connection between the NLRP3 inflammasome and bilirubin toxicity mayprovide a new direction for the development of novel therapeutic approaches in bilirubin toxicity .
Author
![loading ... loading ...](themes/default/img/ajax-loading.gif)
Shelf entry
Permalink
- URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year | Impact factor | Edition | Category | Classification | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Select the library membership card:
If the library membership card is not in the list,
add a new one.
DRS, in which the journal is indexed
Database name | Field | Year |
---|
Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
---|
Source: Personal bibliographies
and: SICRIS
The material is available in full text. If you wish to order the material anyway, click the Continue button.