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Insulin suppresses MPP + -induced neurotoxicity by targeting integrins and syndecans in C6 astrocytes.
- Source :
-
Journal of receptor and signal transduction research [J Recept Signal Transduct Res] 2017 Dec; Vol. 37 (6), pp. 550-559. Date of Electronic Publication: 2017 Aug 30. - Publication Year :
- 2017
-
Abstract
- Parkinson's disease (PD) is the second most common neurodegenerative disease in the elderly. In central nervous system, astrocytes regulates neuronal function via the modulation of synaptic transmission and plasticity, secretion of growth factors, uptake of neurotransmitters and regulation of extracellular ion concentrations and metabolic support of neurons. Therefore, C6 astroglial cells have been used to study the in vitro PD model induced by 1-methyl-4-phenyl pyridinium (MPP <superscript>+</superscript> ). In this study, pre-treatment of insulin inhibited MPP <superscript>+</superscript> -induced cell membrane damages on LDH and NO releases, which also inhibited the iNOS and Cox-2 levels. Insulin also up-regulated the PI3K and p-GSK-3β protein expressions in C6 cells. In addition, MPP <superscript>+</superscript> and/or insulin enhanced the autophagy by increasing LC3-I to LC3-II conversion. Furthermore, MPP <superscript>+</superscript> -induced toxicity diminished the integrin β3, αV, syndecan-1 and -3. Insulin pre-treatment enhanced the phosphorylation of integrin-linked kinase and further induced the integrin and syndecan molecules. These findings suggest that insulin prevents MPP <superscript>+</superscript> -induced toxicity through activation of PI3K, p-GSK-3β, autophagy, integrins and syndecans pathways in C6 glial cells.
- Subjects :
- 1-Methyl-4-phenylpyridinium toxicity
Animals
Apoptosis drug effects
Astrocytes drug effects
Autophagy genetics
Cell Line
Disease Models, Animal
Humans
Insulin pharmacology
Integrin alphaV genetics
Integrin beta3 genetics
Nitric Oxide metabolism
Parkinson Disease genetics
Parkinson Disease pathology
Parkinson Disease, Secondary chemically induced
Parkinson Disease, Secondary pathology
Phosphorylation
Rats
Signal Transduction drug effects
Syndecan-1 genetics
Syndecan-3 genetics
Astrocytes pathology
Autophagy drug effects
Parkinson Disease metabolism
Parkinson Disease, Secondary genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1532-4281
- Volume :
- 37
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of receptor and signal transduction research
- Publication Type :
- Academic Journal
- Accession number :
- 28853308
- Full Text :
- https://doi.org/10.1080/10799893.2017.1369119