Liraglutide Treatment Ameliorates Neurotoxicity Induced by Stable Silencing of Pin1
Abstract
:1. Introduction
2. Results
2.1. In Vitro Modeling of Human Neurodegeneration
2.1.1. Pin1 Silencing Influences Cell Energy Metabolism
2.1.2. Pin1 in Insulin Signaling Cascade. Liraglutide Restored Impaired GSK3β and Akt Activities
2.1.3. Liraglutide Enhanced Cell Viability in Presence of Impaired Glycolysis
2.1.4. Liraglutide Enhances Cell Viability, Anti-Apoptotic Signals and Reduced ROS in Cells Treated with MG
3. Discussion
3.1. Silencing of Pin1 and Cell Energy Metabolism
3.2. Liraglutide Relieves 2DG Induced Neurotoxicity and Enhances Cell Viability in Pin1 KD Clones
3.3. Liraglutide Reduces MG Neurotoxicity: Impaired Cell Viability, ROS Production and Cell Apoptosis
4. Materials and Methods
4.1. Cell Lines and Chemicals
4.2. In Vitro Treatment
4.3. Stable Silencing Pin1 Gene
4.4. Cell Viability Assessment
4.5. Total ATP Content Measurements
4.6. ROS Production
4.7. Quantitative Real Time-PCR
4.8. Western Blotting
4.9. Examination of Apoptosis by Flow Cytometer
4.10. Immunocitochemistry
4.11. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
AD | Alzheimer Disease |
AGEs | Advanced Glycation End-Products |
AMPK | AMP-activated Protein Kinase |
APP | Amyloid Precursor Protein |
Aβ | Amyloid beta |
ATP | Adenosine Triphosphate |
BAX | BCL-2 associated X |
CASP3 | Caspase3 |
2DG | 2-Deoxy-D-Glucose |
DRP1 | Dynamin-Related Protein 1 |
pDRP1(S616) | PhosphoDynamyn Related Protein 1(S616) |
FIS1 | Fission1 |
G | Glucose |
GLP-1 | Glucagon-Like-Peptide1 |
GSK3β | Glycogen Synthase Kinase-3β |
pGSK3β | PhoshoGlycogen Synthase Kinase-3β |
Lira | Liraglutide |
MFN1 | Mitofusin 1 |
MG | MethylGlioxal |
NRF1 | Nuclear Respiratory Factor 1 |
O | Oligomycin |
OPA1 | Optic Atrophy 1 |
P | Parental cells |
P1-A7 | Pin1 KD |
P1-C7 | Pin1 KD |
Pin1 | Peptidylprolyl cis/trans isomerase NIMA-interacting 1 |
Pin1 KD | Pin1 knock down |
PI3K | Phosphoinositol 3 kinase |
PGC1α | Peroxisome proliferator-activated receptor gamma coactivator 1-alpha |
qPCR | Real-time quantitative PCR |
ROS | Reactive Oxygen Species |
Sc | Scramble |
SIRT1 | NAD-dependent deacetylase 1 Sirtuin 1 |
T2D | Type 2 Diabetes |
T3D | Type 3 Diabetes |
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Bianchi, M.; D’Oria, V.; Braghini, M.R.; Petrini, S.; Manco, M. Liraglutide Treatment Ameliorates Neurotoxicity Induced by Stable Silencing of Pin1. Int. J. Mol. Sci. 2019, 20, 5064. https://doi.org/10.3390/ijms20205064
Bianchi M, D’Oria V, Braghini MR, Petrini S, Manco M. Liraglutide Treatment Ameliorates Neurotoxicity Induced by Stable Silencing of Pin1. International Journal of Molecular Sciences. 2019; 20(20):5064. https://doi.org/10.3390/ijms20205064
Chicago/Turabian StyleBianchi, Marzia, Valentina D’Oria, Maria Rita Braghini, Stefania Petrini, and Melania Manco. 2019. "Liraglutide Treatment Ameliorates Neurotoxicity Induced by Stable Silencing of Pin1" International Journal of Molecular Sciences 20, no. 20: 5064. https://doi.org/10.3390/ijms20205064