Anti-apoptotic effects of probucol are associated with downregulation of Daxx expression in THP-1 macrophage.

Abstract:

AIM:To study the relationship between Daxx expression and the antiapoptotic effects of probucol in THP-1 macrophage. MATERIALS AND METHODS:Apoptosis of THP-1 derived macrophages was induced by exposure to oxidized low density lipoprotein (oxLDL). The development of apoptosis was determined by flow cytometry analysis and nucleic acid-binding dye acridin orange. Reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting and indirect immunofluorescence were used to evaluate the expression of Daxx and caspase-3 at both mRNA and protein level. RESULTS:As expected, THP-1 macrophages exposed to 100 mg/l oxLDL for 48 h exhibited typical morphologic changes of apoptosis, including condensed chromatin and shrunken nucleus. oxLDL treatment markedly increased Daxx expression in a time- and dose-dependent manner, and facilitated Daxx translocation from cytoplasm to nucleus. The percentage of cells with Daxx in nuclei was significantly increased from 8 to 59%. Treatment with probucol (50 micromol/l) for 4 h prior to exposure to oxLDL significantly inhibited Daxx expression and THP-1 macrophage apoptosis by 61.3%. Furthermore, oxLDL enhanced caspase-3 expression with increased mRNA and protein levels, but without obvious change in translocation of caspase-3 (the cells with nuclear Daxx: 14 vs 8%). In contrast, probucol attenuated oxLDL-stimulated caspase-3 expression in THP-1 macrophages. CONCLUSION:OxLDL-induced apoptosis of THP-1 macrophage is associated with Daxx up-regulation; while inhibition of apoptosis by probucol is related to decreased Daxx expression and nuclear translocation.

journal_name

Cardiovasc Drugs Ther

authors

Su B,Yang YB,Tuo QH,Zhu BY,Lei XY,Yin W,Liao DF

doi

10.1007/s10557-007-6002-x

subject

Has Abstract

pub_date

2007-02-01 00:00:00

pages

37-45

issue

1

eissn

0920-3206

issn

1573-7241

journal_volume

21

pub_type

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