| Summary: | 碩士 === 輔仁大學 === 生命科學系碩士班 === 102 === There are many factors causing neurodegeneration, including inflammation and local tissue environment change. Releasing of inflammatory cytokine (interleukin-1 beta; IL-1β) and extracellular deposits of fibrils and amorphous aggregates of amyloid beta-peptide (Aβ) caused inflammation and neuronal damage. Moreover, diabetes mellitus causing hyperglycemia changes local tissue environment, and advanced glycation end products (AGEs) produce that accelerated micro- and macro-vascular injury and neuronal damage. Liver X receptor (LXR), one of the nuclear hormone receptor superfamily, which regulate genes involved in cholesterol metabolism and transport, lipoprotein remodeling and lipogenesis, and neuroprotection. Several investigations show that activation of LXR suppress inflammatory responses and neuroprotective effects in the central nervous system. Therefore, we will investigate the effect of neurodegenerative (IL-1β, Aβ(1-42), AGE-BSA) and neural protection (LXR agonist T0901317) factors with cell viability, related gene, protein and microarray analysis in SH-SY-5Y cell line. In the study, after treat with different concentration of IL-1β, Aβ(1-42), AGE-BSA and T0901317 for 72 h in cells, the cell viability was detected by MTT assay and Live/Dead kit. With the increasing IL-1β and AGE-BSA concentration, the cell viability has no significant difference. Moreover, the cell viability has significant difference with increase Aβ(1-42) and T0901317 in concentration. In the next experiment, we selected the concentration of 2.5 M A(1-42) and 0.5 M T0901317 as the cell model. In this model, after treating with T0901317, gene expression detected by Real-time quantitative polymerase chain reaction (Q-PCR), LXR-related genes LXR α and LXR β have significantly increased, and there have no significantly difference in COX4, CREB and NF-κB gene expression. Protein expressed in CREB and NF-κB had no significantly difference. Microarray result shows that treating Aβ(1-42), T0901317 and Aβ(1-42) with T0901317 compare with control have many gene up- or down- regulated. The above effects appeared to be exerted by T0901317 because it affected the SH-SY-5Y cell in Aβ-impairment via LXR.
|
|---|
