High-Cholesterol Diet Decreases the Level of Phosphatidylinositol 4,5-Bisphosphate by Enhancing the Expression of Phospholipase C (PLCβ1) in Rat Brain

• Main Authors: Yoon Sun Chun, Sungkwon Chung
• Format: Article
• Language: English
• Published: MDPI AG 2020-02-01
• Series: International Journal of Molecular Sciences
• Subjects: phosphatidylinositol 4,5-bisphosphate; phospholipase c; cholesterol; high-cholesterol diet
• Online Access: https://www.mdpi.com/1422-0067/21/3/1161

Cholesterol is a critical component of eukaryotic membranes, where it contributes to regulating transmembrane signaling, cell−cell interaction, and ion transport. Dysregulation of cholesterol levels in the brain may induce neurodegenerative diseases, such as Alzheimer’s disease, Parkinson disease, and Huntington disease. We previously reported that augmenting membrane cholesterol level regulates ion channels by decreasing the level of phosphatidylinositol 4,5-bisphosphate (PIP₂), which is closely related to β-amyloid (Aβ) production. In addition, cholesterol enrichment decreased PIP₂ levels by increasing the expression of the β1 isoform of phospholipase C (PLC) in cultured cells. In this study, we examined the effect of a high-cholesterol diet on phospholipase C (PLCβ1) expression and PIP₂ levels in rat brain. PIP₂ levels were decreased in the cerebral cortex in rats on a high-cholesterol diet. Levels of PLCβ1 expression correlated with PIP₂ levels. However, cholesterol and PIP₂ levels were not correlated, suggesting that PIP₂ level is regulated by cholesterol via PLCβ1 expression in the brain. Thus, there exists cross talk between cholesterol and PIP₂ that could contribute to the pathogenesis of neurodegenerative diseases.