mPTP Proteins Regulated by Streptozotocin-Induced Diabetes Mellitus Are Effectively Involved in the Processes of Maintaining Myocardial Metabolic Adaptation
Abstract
:1. Introduction
2. Results
2.1. Biochemical Characterization of the Experimental Model
2.2. Liquid Chromatography and Mass Spectrometry-Based Proteomics
2.2.1. Protein Association Network in STRING
2.2.2. Hypothesis about the Difference between C and D Conditions with Respect to the Different Expressions (Upregulation and Downregulation of Relevant Proteins)
2.2.3. Differentially Expressed Proteins: Between-Group Comparison
2.2.4. Differentially Expressed Proteins: Within-Group Comparison
2.2.5. Cluster Analysis Results
3. Discussion
4. Materials and Methods
4.1. Compliance with Ethical Standards
4.2. Experimental Animals
4.3. Experimentally Induced Acute Streptozotocin Diabetes
4.4. Anesthesia
4.5. Isolation of Mitochondria
4.6. In-Solution Protein Digestion
4.7. Analysis by Nano-Liquid Chromatography and Mass Spectrometry (LC-MS)
4.8. Database Searching and Protein Identification
4.9. Data Analysis and Interpretation
4.10. Statistical Analyses
4.11. Biological Significance Testing
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
ACN | acetonitrile |
ADT | adenine nucleotide translocator |
AST | astaxanthin |
ATP | adenosine triphosphate |
C | healthy control |
CypD | cyclophilin D |
D | diabetes mellitus |
EDTA | ethylenediaminetetraacetic acid |
emPAI | exponentially modified Protein Abundance Index |
FC | fold change |
FDR | false discovery rate |
HK-2 | hexokinase-2 |
I/R | ischemia/reperfusion |
IMM | inner mitochondrial membrane |
LC-MS | liquid chromatography and mass spectrometry |
MP | metabolic preconditioning |
MPCP | mitochondrial phosphate carrier protein |
mPTP | mitochondrial permeability transition pore |
MS | mass spectrometry |
mtCK | mitochondrial creatine kinase |
NADH | nicotinamide adenine dinucleotide |
OMM | outer mitochondrial membrane |
P | probability |
PC | preconditioning |
ROS | reactive oxygen species |
TSPO | translocator protein |
VDAC | voltage-dependent anion channel |
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Metabolic Parameters | C | D |
---|---|---|
Glucose (mmol·L−1) | 6.58 ± 0.48 | 23.56 ± 0,93 ** |
Triacylglycerol (g·L−1) | 1.35 ± 0.17 | 4.84 ± 0.35 ** |
Cholesterol (mmol·L−1) | 1.81 ± 0.17 | 2.48 ± 0.22 * |
Insulin (ng·mL−1) | 1.08 ± 0.2 | 0.43 ± 0.12 ** |
Protein | AVE LOG FC D:C | ANTILOG AVE D:C | p-Value | Two-Way RM ANOVA | ||
---|---|---|---|---|---|---|
Treatment * | Runs * | Interaction * | ||||
ADT1 | 0.0239 | 1.0167 | 0.8137 | 0.8419 | 0.1511 | 0.5467 |
ADT2 | 0.0592 | 1.0419 | 0.686 | 0.5458 | 0.0593 | 0.9187 |
AT5F1 | −0.0012 | 0.9992 | 0.9894 | 0.9567 | 0.0043 | 0.3029 |
ATP5H | 0.4415 | 1.358 | 0.0021 | 0.0006 | 0.0002 | 0.0111 |
ATP5I | 0.0092 | 1.0064 | 0.9582 | 0.9157 | 0.0049 | 0.582 |
ATP5J | 0.3135 | 1.2427 | 0.0188 | 0.0714 | 0.2404 | 0.195 |
ATP5L | −0.0558 | 0.9621 | 0.7055 | 0.3691 | 0.0763 | 0.0731 |
ATPA | 0.0746 | 1.0531 | 0.4434 | 0.3389 | 0.0214 | 0.1822 |
ATPB | 0.0755 | 1.0537 | 0.3352 | 0.1826 | 0.0469 | 0.3286 |
ATPD | −0.0334 | 0.9771 | 0.3519 | 0.1301 | 0.455 | 0.455 |
ATPG | 0.1612 | 1.1182 | 0.1221 | 0.0205 | 0.0043 | 0.53 |
ATPK | 0.2865 | 1.2197 | 0.2668 | 0.2875 | 0.0036 | 0.8797 |
ATPO | 0.0405 | 1.0285 | 0.654 | 0.7228 | 0.0001 | 0.1039 |
KCRS | 0.2803 | 1.2145 | 0.0699 | 0.0002 | <0.0001 | 0.0195 |
MPCP | 0.0597 | 1.0423 | 0.1186 | 0.3071 | 0.6687 | 0.586 |
VDAC1 | 0.1558 | 1.114 | 0.3914 | 0.0497 | 0.005 | 0.1429 |
VDAC2 | −0.0692 | 0.9531 | 0.4733 | 0.6699 | 0.2726 | 0.1745 |
VDAC3 | 0.1216 | 1.088 | 0.1376 | 0.2279 | 0.2051 | 0.1149 |
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Andelova, N.; Waczulikova, I.; Talian, I.; Sykora, M.; Ferko, M. mPTP Proteins Regulated by Streptozotocin-Induced Diabetes Mellitus Are Effectively Involved in the Processes of Maintaining Myocardial Metabolic Adaptation. Int. J. Mol. Sci. 2020, 21, 2622. https://doi.org/10.3390/ijms21072622
Andelova N, Waczulikova I, Talian I, Sykora M, Ferko M. mPTP Proteins Regulated by Streptozotocin-Induced Diabetes Mellitus Are Effectively Involved in the Processes of Maintaining Myocardial Metabolic Adaptation. International Journal of Molecular Sciences. 2020; 21(7):2622. https://doi.org/10.3390/ijms21072622
Chicago/Turabian StyleAndelova, Natalia, Iveta Waczulikova, Ivan Talian, Matus Sykora, and Miroslav Ferko. 2020. "mPTP Proteins Regulated by Streptozotocin-Induced Diabetes Mellitus Are Effectively Involved in the Processes of Maintaining Myocardial Metabolic Adaptation" International Journal of Molecular Sciences 21, no. 7: 2622. https://doi.org/10.3390/ijms21072622