Session: 7

PS7-19 | Copper increases oxidative stress and Cholesterol synthesis in astrocytes

Marlene Zubillaga


It was described that high cholesterol (Cho) levels in membranes favor theamyloidogenic processing of the amyloid precursor protein (APP)in patients with Alzheimer’s disease (AD). Also, Cu may raise the levels of reactive oxygen species (ROS)leading to the production of pro-inflammatory cytokines and the nuclear translocation of SREBP-2. This transcription factor enhances the transcription of genes such as 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and the LDL receptor (LDLR) and thus increases Cho levels.
Astrocytes provide Cho to neurons and become reactive in conditions of neuroinflammation such as in AD, overexpressing glial fibrillary acidic protein (GFAP).
We study the effects of sub-lethal concentrations of Cu exposure on Cho synthesis and the redox status in astrocytes primary cultures of male rats.
We evaluate: Cu concentration; Cho de novo synthesis and total Cho; LDLR and GFAP protein levels; HMGCR,TNFα and SREBP2 mRNA levels, and the redox status by the analysis of TBARS, NOx, protein carbonyls (PCs), and SOD activity.
Data show an increase in HMGCR, SREBP-2 and LDLR, and higher levels of Choafter Cu treatment. Treatment also riseTNFα and GFAP levels. Finally, astrocytes expose to Cu show higher levels of TBARS, NOX, and PCs than control cells. In addition, SOD activity enhancesafter treatment. Our data suggest that Cu addition favor Cho synthesis and uptake in astrocytes in vivo, as well as promote their reactivity.