The carboxyl-terminal cytoplasmic domain of CD36 is required for oxidized low-density lipoprotein modulation of NF-kappaB activity by tumor necrosis factor-alpha.
The binding of oxidized low-density lipoprotein (Ox LDL) by monocyte-macrophages causes pleiotropic effects, including changes in gene expression, and is thought to represent an early event in atherogenesis. The integral membrane glycoprotein CD36 appears to play a physiological role in binding and uptake of Ox LDL by monocyte-macrophages, although the molecular events associated with CD36-Ox LDL interaction are unknown. To approach this issue, we used CD36 transfected Chinese hampster ovary (CHO) cells, exposed them to Ox LDL, and determined changes in the activity of the transcription factor NF-kappaB. We report here that Ox LDL enhanced DNA binding activity of nuclear extracts to an NF-kappaB sequence following activation of CD36-producing CHO cells with the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). This enhanced DNA binding activity was inhibited by coincubation of CD36 transfected cells with the human CD36-specific antibody OKM5. We also determined that activation of NF-kappaB DNA binding activity required an intact carboxyl-terminal cytoplasmic segment on CD36. Our results support the idea that human CD36 mediates signal transduction events in response to Ox LDL.
Lipsky
R H
RH
The Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Eckert
D M
DM
Tang
Y
Y
Ockenhouse
C F
CF
D000818:Animals; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D018955:CD36 Antigens / Q000502:physiology*; D016466:CHO Cells; D002448:Cell Adhesion; D003001:Cloning, Molecular; D006224:Cricetinae; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D010957:Plasmids; D010963:Plasmodium falciparum; D011973:Receptors, LDL / Q000378:metabolism*; D051131:Receptors, Oxidized LDL; D011994:Recombinant Proteins; D051127:Scavenger Receptors, Class E; D015398:Signal Transduction / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D018955:CD36 Antigens; D016328:NF-kappa B; C495137:OLR1 protein, human; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D011994:Recombinant Proteins; D051127:Scavenger Receptors, Class E; D014409:Tumor Necrosis Factor-alpha