title: CD36 overexpression in ritonavir-treated THP-1 cells is reversed by alpha-tocopherol.
abstract: Therapies with antiretroviral protease inhibitors (ARPI) are correlated with a higher risk for dyslipidemia, hypercholesterolemia, and atherosclerosis. The original aim of this study was to establish whether alpha-tocopherol can reduce CD36 scavenger receptor overexpression occurring after treatment of monocytes with the ARPI ritonavir. We show here that treatment of THP-1 monocytes with ritonavir increases total protein and surface expression of CD36; however, only weak changes are observed at the mRNA level, suggesting that CD36 overexpression occurs mainly at the posttranscriptional level. Concentrations of ritonavir that upregulate CD36 expression inhibit proteasome activity in THP-1 cells, indicating a possible regulatory role of the proteasome in CD36 overexpression. Similar to ritonavir, the proteasome inhibitor ALLN increases the CD36 surface expression on THP-1 cells. alpha-Tocopherol efficiently normalizes CD36 protein overexpression after ritonavir treatment and reduces oxLDL uptake. Furthermore, in THP-1 monocytes, alpha-tocopherol reverses the proteasome activity inhibited by ritonavir. This study indicates that an increased CD36 protein expression in THP-1 monocytes induced by ritonavir can be normalized by alpha-tocopherol. CD36 overexpression is caused by inhibition of proteasome activity by ritonavir, which is efficiently restored by alpha-tocopherol.
authors.affiliation: Institute of Biochemistry and Molecular Biology, University of Bern, Bühlstrasse 28, 3012 Bern, Switzerland.
authors.forename: Adelina
authors.initials: A
authors.lastname: Munteanu
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Zingg
authors.forename: Roberta
authors.initials: R
authors.lastname: Ricciarelli
authors.forename: Angelo
authors.initials: A
authors.lastname: Azzi
mesh_terms: D001483:Base Sequence; D018955:CD36 Antigens / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D002784:Cholesterol / Q000097:blood; D017931:DNA Primers; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D061988:Proteasome Inhibitors; D012333:RNA, Messenger / Q000235:genetics; D019438:Ritonavir / Q000494:pharmacology*; D024502:alpha-Tocopherol / Q000494:pharmacology
chemical_list: D018955:CD36 Antigens; D017931:DNA Primers; D017320:HIV Protease Inhibitors; D061988:Proteasome Inhibitors; D012333:RNA, Messenger; D002784:Cholesterol; D024502:alpha-Tocopherol; D019438:Ritonavir