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Insulin-like growth factor type 1 up-regulates uncoupling protein 3
Stockholm University, Faculty of Science, Department of Neurochemistry.
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2001 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 287, no 5, 1105-1111 p.Article in journal (Refereed) Published
Abstract [en]

In this study the expression of uncoupling protein 3 (UCP3) and its regulation by insulin-like growth factor 1 (IGF-I) and insulin in human neuroblastoma SH-SY5Y cells were characterized. Reverse transcriptase-PCR, Western blot, and immunofluorescence analysis showed that SH-SY5Y cells express UCP3 natively. IGF-I induced a time- and concentration-dependent induction of UCP3 protein reaching a twofold expression after 72 h with 10 nM IGF-I. Extremely high insulin concentrations (860 nM) and 10 nM trIGF-I, a truncated form of IGF-I with the same affinity for the IGF-I receptor as the full-length IGF-I, but with lower activity on the insulin receptor, also upregulated UCP3. We conclude that SH-SY5Y cells express UCP3 natively and that the expression is regulated by IGF-I via the IGF-I receptor.

Place, publisher, year, edition, pages
2001. Vol. 287, no 5, 1105-1111 p.
Keyword [en]
uncoupling protein, IGF-I, SH-SY5Y, insulin, diabetes
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:su:diva-22832DOI: 10.1006/bbrc.2001.5702OAI: oai:DiVA.org:su-22832DiVA: diva2:189593
Note
Part of urn:nbn:se:su:diva-121Available from: 2004-04-28 Created: 2004-04-28 Last updated: 2017-12-13Bibliographically approved
In thesis
1. Uncoupling Proteins: Regulation by IGF-1 and Neuroprotection during Hyperglycemia in Vitro
Open this publication in new window or tab >>Uncoupling Proteins: Regulation by IGF-1 and Neuroprotection during Hyperglycemia in Vitro
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Diabetic neuropathy is believed to arise due to oxidative stress following hyperglycemic situations. Uncoupling proteins (UCPs) constitute a subgroup of mitochondrial transporter proteins with putative antioxidant properties. By dissipating the proton gradient over the mitochondrial inner membrane, these proteins reduce the mitochondrial inner membrane potential (MMP), and thereby, the mitochondrial production of reactive oxygen species (ROS) is decreased. In this thesis I have examined the regulation of UCP2, UCP3, and UCP4 by the neuroprotective hormone insulin-like growth factor type 1 (IGF-1). I have also investigated the possible involvement of UCP3 in IGF-1-mediated neuroprotection following high glucose treatments. All studies were performed using human neuroblastoma SH-SY5Y cells as an in vitro cell model. The major findings were as follows:

i. Native SH-SY5Y cells expressed UCP2, UCP3, and UCP4.

ii. UCP3 was upregulated by IGF-1 via activation of the IGF-1 receptor. IGF-1 increased UCP3 mRNA and protein levels primarily via activation of the “classical” anti-apoptotic phosphatidyl inositol 3 (PI3)-kinase signaling pathway, as shown by incubation with specific inhibitors of the PI3-kinase and mitogen activated protein (MAP) kinase signaling pathways.

iii. UCP2 and UCP4 protein levels were only marginally or not at all regulated by IGF-1. These UCPs are probably not involved in IGF-1-mediated neuroprotection.

iv. High glucose concentrations reduced the UCP3 protein levels in highly differentiated SH-SY5Y cells. Concomitantly, the MMP and the levels of ROS and glutathione increased, whereas the number of neurites per cell was reduced. This supports an antioxidant and neuroprotective role of UCP3

v. IGF-1 prevented the glucose-induced reduction in UCP3 protein levels. In parallel, the effects on MMP, levels of ROS and glutathione, and number of neurites per cell were abolished or significantly reduced. These data suggest that UCP3 is involved in IGF-1-mediated neuroprotection.

Place, publisher, year, edition, pages
Stockholm: Institutionen för neurokemi, 2004. 64 p.
Keyword
uncoupling protein, oxidative stress, diabetes, neuropathy, SH-SY5Y
National Category
Neurosciences
Identifiers
urn:nbn:se:su:diva-121 (URN)91-7265-826-6 (ISBN)
Public defence
2004-05-19, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 12 A, Stockholm, 10:00
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Available from: 2004-04-28 Created: 2004-04-28 Last updated: 2010-11-19Bibliographically approved

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