Metabolomic Analysis of Trehalose Alleviating Oxidative Stress in Myoblasts
Abstract
:1. Introduction
2. Results
2.1. Trehalose Attenuated H2O2-Induced Decrease in Myoblast Viability
2.2. Trehalose Facilitated ROS Scavenging in Myoblasts
2.3. Trehalose Altered the Metabolic Profile of Myoblasts
2.4. Identification of Significant Metabolites in Myoblasts
2.5. Trehalose Changed Metabolites Levels in Myoblasts
2.6. Trehalose Altered Metabolic Pathways in Myoblasts
2.7. Trehalose Activated the Nrf2-NQO1 Axis and Promoted the Nuclear Translocation of Nrf2
3. Discussion
3.1. Trehalose Regulates Oxidant Metabolism and Facilitates ROS Scavenging
3.2. Trehalose Regulates Amino Acid Metabolism and the TCA Cycle
3.3. Trehalose Increases the Nuclear Localization of Nrf2 by Increasing the Levels of P62 and Nrf2
4. Materials and Methods
4.1. Reagents
4.2. Cell Culture
4.3. Cell Viability Measurements
4.4. Intracellular ROS Measurements
4.5. Lipid Peroxidation Assessed Using the MDA Assay
4.6. Assay of Cellular T-AOC
4.7. Extraction of Cellular Metabolites
4.8. Acquisition of NMR Spectra
4.9. NMR Data Preprocessing and Resonance Assignments
4.10. Multivariate Analysis and Univariate Analysis of NMR Data
4.11. Metabolic Pathway Analysis
4.12. Inhibition of Nrf2 Activity
4.13. Extraction of Nuclear and Cytoplasmic Proteins
4.14. Measurements of Protein Expressions
4.15. General Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Metabolite | Mean ± SD | t-Test | |||||
---|---|---|---|---|---|---|---|
C | T | H | HT | H vs. C | T vs. C | HT vs. H | |
Pantothenate | 0.038 ± 0.004 | 0.045 ± 0.005 | 0.039 ± 0.006 | 0.042 ± 0.003 | ns | ** | ns |
Leucine | 0.487 ± 0.023 | 0.496 ± 0.023 | 0.488 ± 0.021 | 0.488 ± 0.018 | ns | ns | ns |
Isoleucine | 0.244 ± 0.016 | 0.245 ± 0.010 | 0.247 ± 0.014 | 0.248 ± 0.012 | ns | ns | ns |
Valine | 0.249 ± 0.017 | 0.245 ± 0.011 | 0.252 ± 0.012 | 0.249 ± 0.012 | ns | ns | ns |
Fucose | 0.199 ± 0.017 | 0.198 ± 0.015 | 0.213 ± 0.015 | 0.221 ± 0.011 | ns | ns | ns |
Alanine | 1.411 ± 0.069 | 1.654 ± 0.050 | 1.330 ± 0.046 | 1.563 ± 0.060 | * | **** | **** |
Acetate | 0.213 ± 0.068 | 0.237 ± 0.032 | 0.196 ± 0.033 | 0.210 ± 0.038 | ns | ns | ns |
Proline | 0.109 ± 0.004 | 0.102 ± 0.005 | 0.109 ± 0.005 | 0.104 ± 0.005 | ns | ** | ns |
Glutamate | 0.384 ± 0.024 | 0.414 ± 0.019 | 0.373 ± 0.017 | 0.376 ± 0.022 | ns | ** | ns |
Pyroglutamate | 0.116 ± 0.009 | 0.077 ± 0.005 | 0.116 ± 0.008 | 0.080 ± 0.004 | ns | **** | **** |
Glutamine | 0.189 ± 0.014 | 0.221 ± 0.015 | 0.168 ± 0.014 | 0.206 ± 0.008 | ** | **** | **** |
Dimethylamine | 0.022 ± 0.005 | 0.029 ± 0.022 | 0.009 ± 0.005 | 0.004 ± 0.000 | **** | ns | ns |
Aspartate | 0.041 ± 0.003 | 0.043 ± 0.004 | 0.032 ± 0.007 | 0.029 ± 0.003 | ** | ns | ns |
Trimethylamine | 0.170 ± 0.060 | 0.306 ± 0.337 | 0.045 ± 0.053 | 0.014 ± 0.004 | **** | ns | |
Glutathione | 0.110 ± 0.014 | 0.093 ± 0.010 | 0.125 ± 0.012 | 0.113 ± 0.009 | * | ** | * |
Lysine | 0.106 ± 0.009 | 0.115 ± 0.008 | 0.113 ± 0.012 | 0.123 ± 0.009 | ns | * | ns |
Creatine | 1.568 ± 0.139 | 1.621 ± 0.140 | 1.547 ± 0.143 | 1.551 ± 0.073 | ns | ns | ns |
Phosphocreatine | 1.216 ± 0.173 | 1.133 ± 0.176 | 1.107 ± 0.150 | 0.992 ± 0.099 | ns | ns | ns |
Beta-Alanine | 0.205 ± 0.024 | 0.198 ± 0.017 | 0.200 ± 0.016 | 0.172 ± 0.012 | ns | ns | ** |
Choline | 0.083 ± 0.022 | 0.077 ± 0.013 | 0.152 ± 0.042 | 0.076 ± 0.009 | ** | ns | **** |
PC | 1.976 ± 0.139 | 1.812 ± 0.105 | 1.950 ± 0.189 | 1.642 ± 0.149 | ns | ** | ** |
GPC | 1.484 ± 0.169 | 1.281 ± 0.066 | 1.268 ± 0.189 | 1.132 ± 0.059 | * | ** | ns |
Taurine | 0.438 ± 0.023 | 0.398 ± 0.017 | 0.481 ± 0.013 | 0.433 ± 0.024 | **** | *** | **** |
Glucose | 0.395 ± 0.057 | 0.365 ± 0.052 | 0.276 ± 0.085 | 0.318 ± 0.056 | ** | ns | ns |
Glycine | 2.996 ± 0.165 | 2.896 ± 0.117 | 2.909 ± 0.215 | 2.746 ± 0.117 | ns | ns | ns |
Threonine | 0.183 ± 0.023 | 0.196 ± 0.016 | 0.174 ± 0.004 | 0.186 ± 0.004 | ns | ns | **** |
Myo-inositol | 1.343 ± 0.140 | 1.341 ± 0.078 | 1.287 ± 0.092 | 1.305 ± 0.075 | ns | ns | ns |
Lactate | 1.447 ± 0.102 | 1.429 ± 0.071 | 1.595 ± 0.093 | 1.602 ± 0.072 | ** | ns | ns |
GTP | 0.103 ± 0.008 | 0.099 ± 0.007 | 0.097 ± 0.006 | 0.091 ± 0.006 | ns | ns | ns |
Fumarate | 0.008 ± 0.002 | 0.010 ± 0.001 | 0.008 ± 0.002 | 0.009 ± 0.001 | ns | * | * |
Histidine | 0.023 ± 0.002 | 0.022 ± 0.002 | 0.025 ± 0.002 | 0.024 ± 0.001 | ns | ns | ns |
Tyrosine | 0.169 ± 0.010 | 0.162 ± 0.009 | 0.165 ± 0.006 | 0.162 ± 0.005 | ns | ns | ns |
Phenylalanine | 0.088 ± 0.007 | 0.087 ± 0.004 | 0.086 ± 0.005 | 0.088 ± 0.004 | ns | ns | ns |
AXP | 0.456 ± 0.031 | 0.437 ± 0.019 | 0.417 ± 0.028 | 0.400 ± 0.028 | * | ns | ns |
Formate | 0.021 ± 0.003 | 0.024 ± 0.005 | 0.018 ± 0.001 | 0.020 ± 0.002 | * | ns | * |
Metabolite | Mean ± SD | t-Test | |||
---|---|---|---|---|---|
pC | pH | pTH | pH vs. pC | pTH vs. pH | |
Leucine | 0.338 ± 0.008 | 0.343 ± 0.011 | 0.316 ± 0.011 | ns | **** |
Isoleucine | 0.326 ± 0.009 | 0.336 ± 0.011 | 0.310 ± 0.011 | ns | **** |
Valine | 0.325 ± 0.007 | 0.337 ± 0.011 | 0.310 ± 0.009 | * | **** |
Alanine | 3.369 ± 0.142 | 2.929 ± 0.160 | 2.905 ± 0.231 | **** | ns |
Acetate | 0.397 ± 0.027 | 0.492 ± 0.032 | 0.456 ± 0.030 | **** | * |
Proline | 0.181 ± 0.017 | 0.165 ± 0.012 | 0.157 ± 0.012 | ns | ns |
Glutamate | 2.126 ± 0.094 | 1.819 ± 0.116 | 1.625 ± 0.103 | **** | ** |
Pyroglutamate | 0.218 ± 0.027 | 0.221 ± 0.013 | 0.210 ± 0.009 | ns | ns |
Glutamine | 1.395 ± 0.101 | 1.352 ± 0.079 | 1.418 ± 0.086 | ns | ns |
Dimethylamine | 0.015 ± 0.003 | 0.014 ± 0.003 | 0.011 ± 0.003 | ns | ns |
Aspartate | 0.021 ± 0.008 | 0.021 ± 0.008 | 0.020 ± 0.007 | ns | ns |
Glutathione | 0.266 ± 0.042 | 0.185 ± 0.044 | 0.169 ± 0.047 | ** | ns |
lysine | 0.143 ± 0.021 | 0.170 ± 0.014 | 0.164 ± 0.012 | * | ns |
Creatine | 1.275 ± 0.139 | 1.027 ± 0.084 | 1.093 ± 0.086 | ** | ns |
Phosphocreatine | 0.806 ± 0.050 | 0.779 ± 0.069 | 0.855 ± 0.095 | ns | ns |
Beta-Alanine | 0.030 ± 0.003 | 0.027 ± 0.003 | 0.031 ± 0.003 | ns | * |
Choline | 0.047 ± 0.010 | 0.044 ± 0.008 | 0.052 ± 0.008 | ns | ns |
PC | 1.302 ± 0.174 | 1.072 ± 0.094 | 1.271 ± 0.101 | * | *** |
GPC | 1.023 ± 0.150 | 0.918 ± 0.087 | 1.061 ± 0.106 | ns | ** |
Taurine | 0.563 ± 0.045 | 0.489 ± 0.029 | 0.481 ± 0.035 | ** | ns |
Glucose | 0.484 ± 0.122 | 0.607 ± 0.077 | 0.611 ± 0.092 | ns | ns |
Glycine | 3.758 ± 0.439 | 3.215 ± 0.254 | 2.951 ± 0.247 | * | * |
Threonine | 0.209 ± 0.007 | 0.190 ± 0.011 | 0.197 ± 0.010 | ** | ns |
Myo-inositol | 0.409 ± 0.058 | 0.384 ± 0.038 | 0.482 ± 0.034 | ns | **** |
Lactate | 5.156 ± 0.214 | 5.786 ± 0.164 | 5.812 ± 0.220 | **** | ns |
GTP | 0.103 ± 0.010 | 0.085 ± 0.011 | 0.079 ± 0.010 | ** | ns |
AXP | 0.584 ± 0.056 | 0.469 ± 0.055 | 0.429 ± 0.047 | ** | ns |
Fumarate | 0.005 ± 0.001 | 0.004 ± 0.001 | 0.004 ± 0.001 | ns | ns |
Tyrosine | 0.268 ± 0.005 | 0.270 ± 0.005 | 0.250 ± 0.004 | ns | **** |
Phenylalanine | 0.206 ± 0.004 | 0.209 ± 0.007 | 0.217 ± 0.008 | ns | * |
Tryptophan | 0.017 ± 0.001 | 0.017 ± 0.001 | 0.015 ± 0.001 | ns | ** |
NAD+ | 0.035 ± 0.005 | 0.029 ± 0.004 | 0.030 ± 0.003 | * | ns |
Formate | 0.011 ± 0.003 | 0.009 ± 0.001 | 0.010 ± 0.001 | ns | ns |
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Zhang, S.; Qiu, X.; Zhang, Y.; Huang, C.; Lin, D. Metabolomic Analysis of Trehalose Alleviating Oxidative Stress in Myoblasts. Int. J. Mol. Sci. 2023, 24, 13346. https://doi.org/10.3390/ijms241713346
Zhang S, Qiu X, Zhang Y, Huang C, Lin D. Metabolomic Analysis of Trehalose Alleviating Oxidative Stress in Myoblasts. International Journal of Molecular Sciences. 2023; 24(17):13346. https://doi.org/10.3390/ijms241713346
Chicago/Turabian StyleZhang, Shuya, Xu Qiu, Yue Zhang, Caihua Huang, and Donghai Lin. 2023. "Metabolomic Analysis of Trehalose Alleviating Oxidative Stress in Myoblasts" International Journal of Molecular Sciences 24, no. 17: 13346. https://doi.org/10.3390/ijms241713346