Methionine Supplementation Alleviates the Germ Cell Apoptosis Increased by Maternal Caffeine Intake in a C. elegans Model
Abstract
:1. Introduction
2. Materials and Methods
2.1. C. elegans Strains and Culture
2.2. Quantification of Methionine in CIA Using Gas Chromatography–Time-of-Flight Mass Spectrometry (GCTOF-MS)
2.3. Quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR)
2.4. Germ Cell Apoptosis Assay
2.5. Germ Cell Proliferation Assay
2.6. RNA Interference (RNAi) Assay
2.7. Western Blot Analysis
2.8. Observation of VIT-2::GFP Expression
2.9. Observation of Developmental Stages of Animals
2.10. Statistical Analysis
3. Results
3.1. Maternal Caffeine Intake Causes Alterations in Methionine Metabolism in C. elegans
3.2. Caffeine-Induced Impaired Methionine Cycle Increases Germ Cell Apoptosis in an LIN-35/RB-Dependent Manner
3.3. Methionine Metabolism Is Involved in Physiological Germ Cell Apoptosis and Vitellogenesis
3.4. Methionine Supplementation Alleviates the Effects of Caffeine Intake
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
Abbreviation | Definition |
mel-32 | Serine hydroxymethyltransferase |
mthf-1 | Methylenetetrahydrofolate reductase (NADPH) |
mtrr-1 | Methionine synthase reductase |
sams-1 | S-adenosylmethionine synthase |
metr-1 | 5-methyltetrahydrofolate-homocysteine methyltransferase |
ahcy-1 | Adenosylhomocysteinase |
cep-1 | C. elegans p-53-like protein |
p53 | Tumor protein |
lin-35 | Retinoblastoma-like protein homolog |
RB | Retinoblastoma-associated protein |
ced-9 | Apoptosis regulator |
Bcl-2 | BCL2 apoptosis regulator |
ced-4 | Cell death protein 4 |
Apaf-1 | Apoptotic peptidase activating factor 1 |
ced-3 | Cell death protein 3 subunit p17 |
Caspase | Caspase-3 |
dpl-1 | Vertebrate transcription factor DP-like |
DP | DP transcription factor |
vit-2 | Vitellogenin structural genes (yolk protein genes) |
ced-1 | Cell death abnormality protein 1 |
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mRNA Target | Primer Sequence | GenBank Database | |
---|---|---|---|
act-1 | forward | 5’-CCAGGAATTGCTGATCGTATGCAGAA-3′ | NC_003283.11, Chr V: 11081052.11082415: 133 bp |
reverse | 5’-TGGAGAGGGAAGCGAGGATAG-3′ | ||
sams-1 | forward | 5′-ATTATCAAGGAGCTCGACCT-3′ | NC_003284.9, Chr X: 11965962.11969893: 318 bp |
reverse | 5′-ATGGGAACTCAGAGTGACC-3′ | ||
metr-1 | forward | 5′-GGAGCAGCTACTGGTAGAC-3′ | NC_003280.10, Chr II: 10926561.10931078: 194 bp |
reverse | 5′-CACAGATGGCGAAATTGAGAG-3′ | ||
mtrr-1 | forward | 5′-TACGTTCTTCTCGGTCTCG-3′ | NC_003280.10, Chr II: 9285975.9289132: 121 bp |
reverse | 5′-AGAGCTGTCAGTTGTTTGTC-3′ | ||
mel-32 | forward | 5′-TGACTCATGGATTCTTCACCC-3′ | NC_003281.10, Chr III: 6440148.6442815, complement: 119 bp |
reverse | 5′-GATCAACCTTGTATGGAAGAGAC-3′ | ||
ahcy-1 | forward | 5′-CGATTGCGAGATTGACGTC-3′ | NC_003279.8, Chr I: 6836469.6838140: 221 bp |
reverse | 5′-GTGTAACGGTCAACCTGTG-3′ | ||
mthf-1 | forward | 5′-GTTGAGACCGATGAGAATGC-3 | NC_003280.10, Chr II: 7773908.7777823, complement: 306 bp |
reverse | 5′-TTCATAATGCTTTGGTGACCAG-3′ | ||
lin-35 | forward | 5′-ACTGGAATTCCGTCCACTTG-3′ | NC_003279.8, Chr I: 5807709.5815637: 327 bp |
reverse | 5′-TCCGCTCATCAATACTTCCA-3′ | ||
dpl-1 | forward | 5′-GGTCAGAGATATAGAGTTCGTCC-3′ | NC_003280.10, Chr II: 9169910.9172565: 402 bp |
reverse | 5′-CTGATGTCCAGAAATGCTTCCAG-3′. |
Primer | Primer Sequence |
---|---|
T7 primer | 5′-GTAATACGACTCACTATAGGGC-3′ |
CMo422 primer | 5′-GCGTAATACGACTCACTATAGGGAACAAAAGCTGGAGCT-3′ |
Primary Antibodies | ||||
---|---|---|---|---|
Antigen | Host | Reference | Dilution | |
CED-9 | Rabbit | Santa Cruz Biotechnology, Dallas, TX, USA | 1:500 | |
CED-4 | Goat | Santa Cruz Biotechnology, Dallas, TX, USA | 1:100 | |
α-tubulin | Mouse | Sigma-Aldrich, St. Louis, MO, USA | 1:200 | |
Secondary Antibodies | ||||
Antigen | Host | Reference | Conjugated | Dilution |
Anti-rabbit IgG | Goat | Santa Cruz Biotechnology, Dallas, TX, USA | HRP | 1:10,000 |
Anti-goat IgG | Donkey | Santa Cruz Biotechnology, Dallas, TX, USA | HRP | 1:10,000 |
Anti-mouse IgG | Donkey | Jackson ImmunoResearch, PA, USA | HRP | 1:1000 |
Developmental Stages | Characteristics |
---|---|
L1 stage | smallest larvae less than 0.3 mm |
L2 stage | larva larger than L1 but have no characteristics of L3 (body length, 0.3–0.4 mm) |
L3 stage | larvae containing a white spot at the vulva region (body length, 0.4–0.6 mm) |
L4 stage | larvae containing a half-moon-like shape at the vulva region (body length, 0.6–0.8 mm) |
Adult stage | worms with an opened vulva with eggs in the uterus |
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Min, H.; Kim, J.; Lee, M.; Kang, S.; Shim, Y.-H. Methionine Supplementation Alleviates the Germ Cell Apoptosis Increased by Maternal Caffeine Intake in a C. elegans Model. Nutrients 2024, 16, 894. https://doi.org/10.3390/nu16060894
Min H, Kim J, Lee M, Kang S, Shim Y-H. Methionine Supplementation Alleviates the Germ Cell Apoptosis Increased by Maternal Caffeine Intake in a C. elegans Model. Nutrients. 2024; 16(6):894. https://doi.org/10.3390/nu16060894
Chicago/Turabian StyleMin, Hyemin, Juhae Kim, Mijin Lee, Sangwon Kang, and Yhong-Hee Shim. 2024. "Methionine Supplementation Alleviates the Germ Cell Apoptosis Increased by Maternal Caffeine Intake in a C. elegans Model" Nutrients 16, no. 6: 894. https://doi.org/10.3390/nu16060894