Anserine, a Histidine-Containing Dipeptide, Suppresses Pressure Overload-Induced Systolic Dysfunction by Inhibiting Histone Acetyltransferase Activity of p300 in Mice
Abstract
:1. Introduction
2. Results
2.1. Anserine Suppressed Phenylephrine (PE)-Induced Cardiomyocyte Hypertrophic Responses
2.2. Anserine Suppressed p300-HAT Activity in Cultured Cardiomyocytes and In Vitro
2.3. Marine Active® Suppressed PE-Induced Cardiomyocyte Hypertrophy
2.4. Marine Active® Suppressed Transverse Aortic Constriction (TAC)-Induced Systolic Dysfunction
2.5. Marine Active® Suppressed TAC-Induced Cardiac Hypertrophy
2.6. Marine Active® Suppressed TAC-Induced Cardiac Fibrosis
2.7. Marine Active® Suppressed TAC-Induced Acetylation of Histone H3K9
2.8. Oral Administration of Marine Active® Increased the Content of Anserine in Heart Tissue
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. Animals
4.3. Neonatal Rat Cardiomyocytes
4.4. Fluorescence Staining and Confocal Microscopy
4.5. RNA Isolation and Quantitative Reverse Transcription PCR
4.6. Western Blotting
4.7. In Vitro p300-HAT Assay
4.8. TAC Surgery
4.9. Drug Treatments
4.10. Echocardiography
4.11. Histological Analysis
4.12. Measurement of Anserine Content in Heart Tissue
4.13. Statistics
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Sham | TAC | |||
---|---|---|---|---|
Vehicle | Vehicle | Low Dose of Marine Active® (Anserine 60 mg/kg) | High Dose of Marine Active® (Anserine 200 mg/kg) | |
LVIDs (mm) | 1.33 ± 0.12 | 1.52 ± 0.17 | 1.39 ± 0.13 | 1.15 ± 0.09 ## |
LVIDd (mm) | 2.50 ± 0.17 | 2.35 ± 0.21 | 2.24 ± 0.17 | 2.18 ± 0.21 * |
PWd (mm) | 1.19 ± 0.10 | 1.77 ± 0.11 ** | 1.72 ± 0.14 ** | 1.38 ± 0.12 *## |
IVSd (mm) | 1.21 ± 0.10 | 1.66 ± 0.15 ** | 1.63 ± 0.13 ** | 1.39 ± 0.10 *## |
FS (%) | 46.6 ± 3.6 | 35.5 ± 3.2 ** | 38.1 ± 1.5 ** | 47.0 ± 2.2 ## |
EF (%) | 83.9 ± 3.5 | 72.2 ± 3.7 ** | 75.4 ± 2.1 ** | 84.4 ± 2.4 ## |
HR (bpm) | 573 ± 20 | 607 ± 17 | 620 ± 12 | 626 ± 10 |
BW (g) | 27.0 ± 1.6 | 27.3 ± 1.9 | 26.8 ± 2.1 | 26.3 ± 1.4 |
Target Gene | Forward | Reverse |
---|---|---|
Nppa (ANF) | 5′-AGGCCATATTGGAGCAAATC-3′ | 5′-CATCTTCTCCTCCAGGTGGT-3′ |
Nppb (BNP) | 5′-GATTCTGCTCCTGCTTTTCC-3′ | 5′-CATCGTGGATTGTTCTGGAG-3′ |
Col1a1 (Collagen alpha 1) | 5′-AAGAAGACATCCCTGAAGTCA-3′ | 5′-TTGTGGCAGATACAGATCAAG-3′ |
Col3a1 (Collagen 3 alpha 1) | 5′-CCCAACCCAGAGATCCCATT-3′ | 5′-GAAGCACAGGAGCAGGTGTAGA-3′ |
RNA18S1 (18S) | 5′-CTTAGAGGGACAAGTGGCG-3′ | 5′-GGACATCTAAGGGCATCACA-3′ |
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Sunagawa, Y.; Tsukabe, R.; Irokawa, Y.; Funamoto, M.; Suzuki, Y.; Yamada, M.; Shimizu, S.; Katanasaka, Y.; Hamabe-Horiike, T.; Kawase, Y.; et al. Anserine, a Histidine-Containing Dipeptide, Suppresses Pressure Overload-Induced Systolic Dysfunction by Inhibiting Histone Acetyltransferase Activity of p300 in Mice. Int. J. Mol. Sci. 2024, 25, 2344. https://doi.org/10.3390/ijms25042344
Sunagawa Y, Tsukabe R, Irokawa Y, Funamoto M, Suzuki Y, Yamada M, Shimizu S, Katanasaka Y, Hamabe-Horiike T, Kawase Y, et al. Anserine, a Histidine-Containing Dipeptide, Suppresses Pressure Overload-Induced Systolic Dysfunction by Inhibiting Histone Acetyltransferase Activity of p300 in Mice. International Journal of Molecular Sciences. 2024; 25(4):2344. https://doi.org/10.3390/ijms25042344
Chicago/Turabian StyleSunagawa, Yoichi, Ryosuke Tsukabe, Yudai Irokawa, Masafumi Funamoto, Yuto Suzuki, Miho Yamada, Satoshi Shimizu, Yasufumi Katanasaka, Toshihide Hamabe-Horiike, Yuto Kawase, and et al. 2024. "Anserine, a Histidine-Containing Dipeptide, Suppresses Pressure Overload-Induced Systolic Dysfunction by Inhibiting Histone Acetyltransferase Activity of p300 in Mice" International Journal of Molecular Sciences 25, no. 4: 2344. https://doi.org/10.3390/ijms25042344