PI3-K- and PKC-dependent up-regulation of APP processing enzymes by retinoic acid
2008 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 365, no 2, 298-303 p.Article in journal (Refereed) Published
Retinoic acid stimulates α-secretase processing of amyloid precursor protein (APP) and decreases β-secretase cleavage that leads to amyloid-β formation. Here, we investigated the effect of retinoic acid on the two putative α-secretases, the disintegrin metalloproteinases ADAM10 and TACE, and the β-site cleaving enzyme BACE1, in human neuroblastoma SH-SY5Y cells. Western blot analysis showed that exposure to retinoic acid resulted in significantly increased levels of ADAM10 and TACE, suggesting that regulation of α-secretases causes the effects on APP processing. The presence of the phosphatidylinositol 3-kinase inhibitor LY 294002 selectively reduced the effect on ADAM10 protein levels but not on ADAM10 mRNA levels as determined by RT-PCR. On the other hand, the effect on TACE was shown to be dependent on protein kinase C, since it was completely blocked in the presence of the inhibitor bisindolylmaleimide XI. Our data indicate that different signalling pathways are involved in retinoic acid-induced up-regulation of the secretases.
Place, publisher, year, edition, pages
2008. Vol. 365, no 2, 298-303 p.
ADAM10, APP, BACE1, BDNF, PI3-kinase, Protein kinase C, Retinoic acid, TACE
IdentifiersURN: urn:nbn:se:su:diva-19985DOI: 10.1016/j.bbrc.2007.10.167ISI: 000251494000015OAI: oai:DiVA.org:su-19985DiVA: diva2:186510