Glucosamine-induced attenuates apolipoprotein B100 synthesis via PERK signaling

Wei Qiu, Qiaozhu Su, Khosrow Adeli

Research output: Contribution to journalArticlepeer-review

Abstract

Here , we report that glucosamine also regulates apoB100 protein synthesis via ER-stress-induced PERK activation. Short-term (4 h) glucosamine treatment of HepG2 cells reduced both cellular
(by 62%) and secreted apoB100 (by 43%) without altering
apoB100 mRNA. Treatment with proteasomal inhibitors
only partially prevented the suppressive effects of glucosamine,
suggesting that mechanisms other than proteasomal
degradation may also be involved. Glucosamine-induced
ER stress was associated with a signifi cantly reduced apoB100 synthesis with no signifi cant change in posttranslational decay rates, suggesting that glucosamine exerted its effect early during apoB biosynthesis. The role of PERK and its substrate, α-subunit of eukaryotic initiation factor 2 (eIF2α ), in the suppressive effects of glucosamine on apoB synthesis was then investigated. Coexpression of apoB15 (normally resistant to intracellular degradation) with wildtype double stranded (ds) RNA activated protein kinase (PKR)-like endoplasmic reticulum kinase (PERK) in COS-7 cells resulted in a dramatic reduction in the levels of newly
synthesized apoB15. Interestingly, cotransfection with apoB15 and a kinase inactive PERK mutant (K618A) increased apoB15 expression. In addition, short-term glucosamine treatment stimulated an increase in phosphorylation of PERK and eIF2α. Taken together, these data suggest that in addition to the induction of ER-associated degradation and other degradative pathways, ER stress is associated with suppression of apoB synthesis via a PERK-dependent mechanism.
Original languageEnglish
Article numberPMID:19383982
Pages (from-to)1814-1823
Number of pages9
JournalJournal of Lipid Research
Volume50
DOIs
Publication statusPublished - 21 Apr 2009

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