CD36 overexpression in ritonavir-treated THP-1 cells is reversed by α-tocopherol

Adelina Munteanu, Jean Marc Zingg, Roberta Ricciarelli, Angelo Azzi

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

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 α-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. α-Tocopherol efficiently normalizes CD36 protein overexpression after ritonavir treatment and reduces oxLDL uptake. Furthermore, in THP-1 monocytes, α-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 α-tocopherol. CD36 overexpression is caused by inhibition of proteasome activity by ritonavir, which is efficiently restored by α-tocopherol.

Original languageEnglish (US)
Pages (from-to)1047-1056
Number of pages10
JournalFree Radical Biology and Medicine
Volume38
Issue number8
DOIs
StatePublished - Apr 15 2005
Externally publishedYes

Keywords

  • Atherosclerosis
  • Endocytosis
  • Free radicals
  • Lipoproteins
  • Proteasome
  • Ritonavir
  • Vitamin E

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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