Signalling pathways for insulin-like growth factor type 1-mediated expression of uncoupling protein 3.
2004 (English)In: J Neurochem, ISSN 0022-3042, Vol. 88, no 2, 462-8 p.Article in journal (Refereed) Published
Uncoupling protein 3 (UCP3) is a mitochondrial protein with antioxidant properties and its regulation by factors promoting cell-survival may be important for protection of, for instance, neurons in states of oxidative stress. In the present study, we investigated regulatory pathways for UCP3 expression mediated by the neuroprotective hormone insulin-like growth factor type 1 (IGF-1) in human neuroblastoma SH-SY5Y cells. Northern blot analysis and RT-PCR showed that treatment with 10 nm IGF-1 increased the UCP3 mRNA levels 2.5-fold after 5 h. Co-incubation with the phosphatidylinositol 3 (PI3)-kinase inhibitor LY294002 prohibited IGF-1-mediated induction of both UCP3 mRNA and protein in a concentration-dependent manner, with a complete blockage at 1 microm, as shown by RT-PCR and western blot analyses. The mitogen-activated protein (MAP) kinase kinase 1 (MKK1 or MEK) inhibitor PD98059 also decreased the UCP3 mRNA expression at 10 microm, however, this concentration only partly inhibited the protein expression. We conclude that IGF-1 enhanced UCP3 expression at transcriptional level, primarily through the PI3-kinase-dependent pathway and partly through the MAP kinase pathway.
Place, publisher, year, edition, pages
2004. Vol. 88, no 2, 462-8 p.
1-Phosphatidylinositol 3-Kinase/physiology, Carrier Proteins/*biosynthesis/genetics, Cell Line; Tumor, Gene Expression Regulation/*physiology, Humans, Insulin-Like Growth Factor I/*physiology, Ion Channels, MAP Kinase Signaling System/physiology, Mitochondrial Proteins, Signal Transduction/*physiology
Cell and Molecular Biology
IdentifiersURN: urn:nbn:se:su:diva-20500PubMedID: 14690534OAI: oai:DiVA.org:su-20500DiVA: diva2:187026