Details

Autor(en) / Beteiligte

• Okoro, Emmanuel U.
• Guo, Zhongmao
• Yang, Hong

Titel

Akt isoform-dependent regulation of ATP-Binding cassette A1 expression by apolipoprotein E

Ist Teil von

• Biochemical and biophysical research communications, 2016-08, Vol.477 (1), p.123-128

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• We previously reported that apolipoprotein E (apoE) upregulates ATP-binding cassette transporter A1 (ABCA1) transcription through phosphatidylinositol 3-kinase (PI3K). Here we demonstrate that treatment of murine macrophages with human apoE3 enhanced Akt phosphorylation, and upregulated ABCA1 protein and mRNA expression. Inhibition of PI3K weakened apoE3-induced Akt phosphorylation, and ABCA1 protein and mRNA increase. In contrast, inhibition of Akt only diminished apoE-induced ABCA1 protein but not the mRNA level. Suppression of protein synthesis did not erase the ability of apoE3 to increase ABCA1 protein level. Further, apoE3 increased the resistance of ABCA1 protein to calpain-mediated degradation without affecting calpain activity. Treatment of macrophages with apoE3 selectively enhanced the phosphorylation of Akt1 and Akt2, but not Akt3. Knockdown of Akt1 or Akt2 increased and decreased ABCA1 protein level, respectively; while overexpression of these Akt isoenzymes caused changes in ABCA1 protein level opposite to those induced by knockdown of the corresponding Akt. These data imply that apoE3 guards against calpain-mediated ABCA1 degradation through Akt2. •Apolipoprotein E3 (apoE3) enhances Akt1 and Akt2 phosphorylation.•Inhibition of Akt diminishes apE3-induced ABCA1 protein but not mRNA.•ApE3-increased ABCA1 protein is reduced by Akt2 but not by Akt1 knockdown.