α-Tocopheryl Phosphate Induces VEGF Expression via CD36/PI3Kγ in THP-1 Monocytes

Area of Science:

• Cell Biology
• Molecular Biology
• Immunology

Background:

• The CD36 scavenger receptor plays a role in ligand uptake, signal transduction, and gene expression, potentially involving receptor internalization.
• Understanding the mechanisms of CD36-mediated ligand uptake and signaling is crucial for deciphering its role in cellular processes and disease.

Purpose of the Study:

• To investigate the role of alpha-tocopherol (αT) and alpha-tocopheryl phosphate (αTP) in CD36 internalization and function in THP-1 monocytes.
• To elucidate the signaling pathways involved in αTP-induced vascular endothelial growth factor (VEGF) expression mediated by CD36.

Main Methods:

• Investigated CD36 internalization triggered by αT, αTP, and EPC-K1 in THP-1 monocytes.
• Utilized specific inhibitors like sulfo-N-succinimidyl oleate (SSO) and Dynasore to probe CD36-mediated transport and endocytosis pathways.
• Assessed changes in neutral lipid content, phagocytosis, and VEGF promoter activity using various biochemical and cellular assays.

Main Results:

• αTP and EPC-K1, but not αT, strongly triggered CD36 internalization, which was sensitive to SSO, indicating involvement in αTP uptake.
• αT uptake was primarily mediated by clathrin-dependent endocytosis, distinct from αTP uptake mechanisms.
• αTP and EPC-K1 reduced neutral lipid content and Staphylococcus aureus phagocytosis; αTP induced VEGF expression via the CD36/PI3Kγ/Akt pathway.

Conclusions:

• αTP binding to and/or transport by CD36 mediates cellular αTP uptake and subsequent activation of PI3Kγ/Akt signaling, leading to VEGF expression in monocytes.
• Differential uptake mechanisms of αT and αTP by monocytes influence their signaling effects, with αTP playing a significant role in CD36-mediated angiogenesis regulation.