Effects of hydrogen peroxide and apolipoprotein E isoforms on apolipoprotein E trafficking in HepG2 cells

Tharani Sabaretnam, Matthew Harris, Maaike Kockx, Paul Witting, David Le Couteur, Leonard Kritharides

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)

Abstract

1. The major source of apolipoprotein E (apoE) is the liver. In the present study, the effects of oxidative stress and apoE isoforms on apoE distribution and trafficking were established using the HepG2 liver tumour cell line. 2. Hydrogen peroxide (0, 25, 250 and 1000 micromol/L) was associated with rapid and concentration-dependent redistribution of apoE into the early endosomal compartment. This redistribution was achieved with a much lower concentration (25 micromol/L) than that needed to induce changes in intracellular apoE mRNA expression, apoE protein levels and markers of oxidative stress (250-1000 micromol/L). 3. Live cell imaging of apoE3-green fluorescent protein revealed a significant decrease in traffic velocity in response to oxidative stress. 4. The E4 isoform was associated with reduced trafficking velocity compared with the E3 isoform under basal conditions. 5. The results indicate that oxidative stress and apoE isoforms influence apoE trafficking and distribution within HepG2 cells. Altered apoE hepatocyte trafficking may provide a mechanistic link between oxidative stress, ageing and some diseases in older people.
Original languageEnglish
Pages (from-to)96 - 102
Number of pages7
JournalClinical and Experimental Pharmacology and Physiology
Volume36
Issue number12
DOIs
Publication statusPublished - 2009
Externally publishedYes

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