Antiaging Effect of 4-N-Furfurylcytosine in Yeast Model Manifests through Enhancement of Mitochondrial Activity and ROS Reduction
Abstract
:1. Introduction
2. Materials and Methods
2.1. 4-N-Furfurylcytosine
2.2. Yeast Strain and Media
2.3. CLS Analysis
2.4. Growth Kinetics
2.5. Flow Cytometry Analyses
2.5.1. Effect of FC on MMP
2.5.2. Protective Effect against H2O2
2.5.3. Regenerative Effect after H2O2 Treatment
2.5.4. ROS Measurement
2.6. Confocal Microscopy Analyses
2.6.1. FC Effect on the Yeast Cell Viability
2.6.2. Mitochondrial Membrane Potential
2.6.3. Comparative Analysis of Maturity and Cell Size after FC Treatment
2.7. Respiration Rate Analysis
2.8. Real-Time PCR
2.8.1. Total RNA Isolation
2.8.2. cDNA Synthesis and qPCR
2.9. Statistical Analysis
3. Results
3.1. FC Supplementation Extends Yeast Survival
3.2. FC Strongly Enhances Mitochondrial Performance in Glucose Medium and Also Reduces ROS Level
3.3. FC Exerts Both Protective and Regenerative Effects on Yeast Treated with H2O2
3.4. Effect of FC on the Expression Level of Genes Involved in Metabolism and Stress Resistance in Yeast Cells
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Gene | Forward Primer (5′–3′) | Reverse Primer (5′–3′) | UPL |
---|---|---|---|
CCS1 | TGAACCACCCAGAAAACGA | GCAATGACTCCCAGAAATGAG | 69 |
ECL1 | AATAAGTTATATTGCTCCGAAGATTGT | TTTTATGCAAGTGGGATAATAATTTCT | 161 |
FOB1 | CGAAACGTAAACCTGTGCAA | CTCTCTTAGTCTCAAACTTGGCATT | 85 |
GTR1 | AAGATGGATCTTGTTCAGTTGGA | CAGGTTTTTCATCATGATTTGG | 17 |
HAP4 | TCAGGATGAAAGCGCTGATT | AGCCAAAGTGATTTCTGAACCT | 9 |
RIM15 | TTTCCCTCCTTGATATTTCTCG | TCGAATTTGTGGGATTTGCT | 63 |
SCH9 | TTGGGATCTCACTCGGAATTA | GGATACAGTCTAACTTGGCCTAAGAA | 44 |
SOD2 | AAACCACTGTCTATTCTGGGAAA | CTCGTCGATTGCCTTTGC | 36 |
ACT1 * | TTCCAGATGGTCAAGTCATCA | AAACAGAAGGATGGAACAAAGC | 45 |
ALG9 * | CAAGAGCATGCTTAGGCTTTTT | CCCGGATTAAACAATTGGAA | 27 |
TAF10 * | GAGGAGATTCTAGAGATGATGGACA | AGTCTATTACTGCATCGGGAATG | 63 |
TFC1 * | CTCAAATGCCATAGAGGAGGA | TGGCGCCATTATCATCAAA | 9 |
UBC6 * | AGGCTCACAAGAGATTGACGA | GGGCGAGCAAGAATATATGG | 31 |
Day of CLS | FC (mM) | |||
---|---|---|---|---|
Ctrl | 0.25 | 0.5 | 1.0 | |
3 | 99.4 ± 0.001 | 99.6 ± 0.007 | 99.7 ± 0.002 | 100.0 ± 0.000 |
5 | 98.1 ± 1.285 | 98.8 ± 0.957 | 98.4 ± 1.603 | 98.8 ± 1.341 |
7 | 93.9 ± 3.893 | 96.3 ± 2.813 | 95.9 ± 3.553 | 98.3 ± 1.192 |
10 | 92.1 ± 2.616 | 92.1 ± 2.616 | 93.3 ± 2.951 | 96.2 ± 1.259 |
12 | 81.9 ± 6.879 | 84.6 ± 9.620 | 88.0 ± 8.443 | 91.5 ± 3.888 * |
14 | 74.1 ± 1.401 | 81.7 ± 6.798 | 84.5 ± 7.386 * | 90.5 ± 1.050 **** |
17 | 62.6 ± 6.130 | 73.5 ± 5.770 ** | 80.8 ± 6.503 **** | 88.8 ± 0.656 **** |
19 | 53.1 ± 14.623 | 70.6 ± 2.512 **** | 73.2 ± 4.595 **** | 81.1 ± 0.403 **** |
Cellular Significance | Gene | Changes in Expression Level | Function | |
---|---|---|---|---|
Antioxidant defense | CCS1 | Copper chaperone for SOD1 | ↓↓ | Involved in oxidative stress protection; increase in protein abundance in response to DNA replication stress [32] |
SOD2 | Superoxide dismutase | No change | Mitochondrial manganese superoxide dismutase; protects cells against oxygen toxicity and oxidative stress [32] | |
Nutrient sensing and TORC1 signaling pathway | GTR1 | GTP-binding protein resemblance | ↓↓↓ | GTPase that activates TORC1 in response to amino acid stimulation [33] |
RIM15 | Regulator of IME2 | ↑↑ | Protein kinase involved in cell proliferation in response to nutrients; plays a crucial role in the entry of cells into the stationary phase upon nutrient starvation conditions [34,35,36] | |
SCH9 | Serine/threonine protein kinase | ↓↓↓ | Direct downstream protein kinase of TORC1 [34,35,36] | |
Replication process | FOB1 | Fork blocking less | ↓↓ | Required for replication fork blocking; involved in ERCs generation [37] |
Respiratory activity | HAP4 | Heme activator protein | ↑ | Transcriptional activator and global regulator of respiratory gene expression; plays a central role in shifting cells from fermentative to respiratory growth [38,39] |
Unknown function | ECL1 | Extender of the chronological lifespan | No change | Mitochondrial-dependent role in the extension of CLS; unknown exact molecular function [40] |
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Pawelczak, P.; Fedoruk-Wyszomirska, A.; Wyszko, E. Antiaging Effect of 4-N-Furfurylcytosine in Yeast Model Manifests through Enhancement of Mitochondrial Activity and ROS Reduction. Antioxidants 2022, 11, 850. https://doi.org/10.3390/antiox11050850
Pawelczak P, Fedoruk-Wyszomirska A, Wyszko E. Antiaging Effect of 4-N-Furfurylcytosine in Yeast Model Manifests through Enhancement of Mitochondrial Activity and ROS Reduction. Antioxidants. 2022; 11(5):850. https://doi.org/10.3390/antiox11050850
Chicago/Turabian StylePawelczak, Paweł, Agnieszka Fedoruk-Wyszomirska, and Eliza Wyszko. 2022. "Antiaging Effect of 4-N-Furfurylcytosine in Yeast Model Manifests through Enhancement of Mitochondrial Activity and ROS Reduction" Antioxidants 11, no. 5: 850. https://doi.org/10.3390/antiox11050850
APA StylePawelczak, P., Fedoruk-Wyszomirska, A., & Wyszko, E. (2022). Antiaging Effect of 4-N-Furfurylcytosine in Yeast Model Manifests through Enhancement of Mitochondrial Activity and ROS Reduction. Antioxidants, 11(5), 850. https://doi.org/10.3390/antiox11050850