Targeting Mitochondria by SS-31 Ameliorates the Whole Body Energy Status in Cancer- and Chemotherapy-Induced Cachexia
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Targeting Cardiolipin with SS-31 Partially Ameliorates Cachexia without Interfering with Tumor Growth
2.2. SS-31 Improves Muscle Energetics, Not Mitochondrial Quantity
2.3. Increasing SS-31 Dosage Is More Effective at Intermediate Time Points before Refractory Cachexia Onset
2.4. Muscle, Liver and Plasma Metabolomes Reveal SS-31 Improvement of Systemic Energy Status
3. Discussion
4. Materials and Methods
4.1. Reagents
4.2. Animals and Experimental Design
4.3. Mass Spectrometry Lipidomic Analysis
4.4. Flow Cytometry
4.5. Grasping Test
4.6. Histology and Succinate DeHydrogenase (SDH) Staining and Enzymatic Activity
4.7. ATP intracellular Content
4.8. Western Blotting
4.9. Muscle Protein Synthesis: In Vivo Surface Sensing of Translation
4.10. Ex-Vivo Mitochondrial Respiration Assay
4.11. Metabolomics Analysis by Nuclear Magnetic Resonance
4.12. Glycogen Assay
4.13. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
9-AA | 9-Aminoacridine |
ADP | Adenosine diphosphate |
ANOVA | Analysis of variance |
ATP | Adenosine triphosphate |
BSA | Bovine serum albumin |
C26 | Colon-26 carcinoma |
CL | Cardiolipin |
COX IV | Cytochrome c oxidase |
CSA | Cross-sectional area |
DMEM | Dulbecco’s Modified Eagle’s Medium |
DCPIP | 2,6-Dichlorophenolindophenol |
DSS | 2,2,-dimethyl-2-silapentane-5-sulfonate sodium salt |
EDTA | Ethylenediaminetetraacetic acid |
EGTA | Ethylene glycol tetraacetic acid |
FBS | Fetal bovine serum |
GAPDH | Glyceraldehyde 3-phosphate dehydrogenase |
HEPES | 4-(2-Hydroxyethyl)-1-piperazineethanesulfonic acid |
IgG | Immunoglobulin G |
i.p. | Intraperitoneal |
MALDI-TOF | Matrix assisted laser desorption ionization-time of flight |
NAD | Nicotinamide adenine dinucleotide |
NFDM | Non-fat dry milk |
NMR | Nuclear magnetic resonance |
OCR | Oxygen consumption rate |
OXFU | Oxaliplatin plus 5-fluorouracil |
PBS | Phosphate buffered saline |
PG | Phosphatidylglycerol |
PGC-1α | Peroxisome proliferator-activated receptor gamma coactivator 1 alpha |
ROS | Reactive oxygen species |
RT | Room temperature |
RT-PCR | Quantitative reverse transcription polymerase chain reaction |
SDH | Succinate dehydrogenase |
SDS-PAGE | Sodium dodecyl sulphate polyacrylamide gel electrophoresis |
SEM | Standard error of the mean |
SS-31 | Szeto-Schiller peptide 31 |
SUnSET | Surface sensing of translation |
TA | Tibialis anterior |
TB | Tumour-bearing |
TBS | Tris-buffered saline |
WAT | White adipose tissue |
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Ballarò, R.; Lopalco, P.; Audrito, V.; Beltrà, M.; Pin, F.; Angelini, R.; Costelli, P.; Corcelli, A.; Bonetto, A.; Szeto, H.H.; O’Connell, T.M.; Penna, F. Targeting Mitochondria by SS-31 Ameliorates the Whole Body Energy Status in Cancer- and Chemotherapy-Induced Cachexia. Cancers 2021, 13, 850. https://doi.org/10.3390/cancers13040850
Ballarò R, Lopalco P, Audrito V, Beltrà M, Pin F, Angelini R, Costelli P, Corcelli A, Bonetto A, Szeto HH, O’Connell TM, Penna F. Targeting Mitochondria by SS-31 Ameliorates the Whole Body Energy Status in Cancer- and Chemotherapy-Induced Cachexia. Cancers. 2021; 13(4):850. https://doi.org/10.3390/cancers13040850
Chicago/Turabian StyleBallarò, Riccardo, Patrizia Lopalco, Valentina Audrito, Marc Beltrà, Fabrizio Pin, Roberto Angelini, Paola Costelli, Angela Corcelli, Andrea Bonetto, Hazel H. Szeto, Thomas M. O’Connell, and Fabio Penna. 2021. "Targeting Mitochondria by SS-31 Ameliorates the Whole Body Energy Status in Cancer- and Chemotherapy-Induced Cachexia" Cancers 13, no. 4: 850. https://doi.org/10.3390/cancers13040850