Spermidine ameliorates liver ischaemia-reperfusion injury through the regulation of autophagy by the AMPK-mTOR-ULK1 signalling pathway
Open accessAbstract
BACKGROUND: Hepatic ischaemia-reperfusion (IR) injury is a common clinical challenge lacking effective therapy. The aim of this study was to investigate whether spermidine has protective effects against hepatic IR injury through autophagy. METHODS: Liver ischaemia reperfusion was induced in male C57BL/6 mice. Then, liver function, histopathology, cytokine production and immunofluorescence were evaluated to assess the impact of spermidine pre-treatment on IR-induced liver injury. Autophagosome formation was observed by transmission electron microscopy. Western blotting was used to explore the underlying mechanism and its relationship with autophagy, and TUNEL staining was conducted to determine the relationship between apoptosis and autophagy in the ischaemic liver. RESULTS: The results of the transaminase assay, histopathological examination, and pro-inflammatory cytokine production and immunofluorescence evaluations demonstrated that mice pre-treated with spermidine showed significantly preserved liver function. Further experiments demonstrated that mice administered spermidine before the induction of IR exhibited increased autophagy via the AMPK-mTOR-ULK1 pathway, and TUNEL staining revealed that spermidine attenuated IR-induced apoptosis in the liver. CONCLUSIONS: Our results provide the first line of evidence that spermidine provides protection against IR-induced injury in the liver by regulating autophagy through the AMPK-mTOR-ULK1 signalling pathway. These results suggest that spermidine may be beneficial for hepatic IR injury.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Spermidine induces autophagy by inducing synthesis of TFEB through the AMPK-mTORC1-ULK1 pathway.
“Spermidine induces autophagy by inducing the synthesis of the autophagy transcription factor TFEB [278] through the AMPK–mTORC1–ULK1 pathway [274].”
From The mitochondrial permeability transition: Nexus of aging, disease and longevity (2021) · cites this paper as [274]
Spermidine induces autophagy.
“Spermidine is a known inducer of autophagy [263,274]”
From The mitochondrial permeability transition: Nexus of aging, disease and longevity (2021) · cites this paper as [274]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Autophagy: process and functionPreprint
Mizushima, N. (2007) · Genes & Development · doi:10.1101/gad.1599207 · Cited by 3,967 · see citing works
Phosphorylation of ULK1 (hATG1) by AMP-Activated Protein Kinase Connects Energy Sensing to Mitophagy
Egan, D. F., Shackelford, D. B., Mihaylova, M. M., Gelino, S., Kohnz, R. A., Mair, W., Vasquez, D. S., Joshi, A., Gwinn, D. M., Taylor, R., et al. (2011) · Science · doi:10.1126/science.1196371 · Cited by 2,600 · see citing works
Induction of autophagy by spermidine promotes longevity
Eisenberg, T., Knauer, H., Schauer, A., Büttner, S., Ruckenstuhl, C., Carmona-Gutierrez, D., Ring, J., Schroeder, S., Magnes, C., Antonacci, L., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1975 · Cited by 1,680 · see citing works
Cardioprotection and lifespan extension by the natural polyamine spermidine
Eisenberg, T., Abdellatif, M., Schroeder, S., Primessnig, U., Stekovic, S., Pendl, T., Harger, A., Schipke, J., Zimmermann, A., Schmidt, A., et al. (2016) · Nature Medicine · doi:10.1038/nm.4222 · Cited by 1,168 · see citing works
Spermidine in health and disease
Madeo, F., Eisenberg, T., Pietrocola, F., & Kroemer, G. (2018) · Science · doi:10.1126/science.aan2788 · Cited by 1,154 · see citing works
Ischaemia–reperfusion injury in liver transplantation—from bench to bedside
Zhai, Y., Petrowsky, H., Hong, J. C., Busuttil, R. W., & Kupiec‐Weglinski, J. W. (2012) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2012.225 · Cited by 848 · see citing works
Functions of Polyamines in Mammals
Pegg, A. E. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.r116.731661 · Cited by 720 · see citing works
Autophagy, Metabolism, and Cancer
White, E., Mehnert, J. M., & Chan, C. S. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-0490 · Cited by 669 · see citing works
Caloric restriction mimetics enhance anticancer immunosurveillance
Pietrocola, F., Pol, J., Vacchelli, E., Rao, S., Enot, D. P., Baracco, E. E., Levesque, S., Castoldi, F., Jacquelot, N., Yamazaki, T., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.05.016 · Cited by 542 · see citing works
Ischaemia reperfusion injury in liver transplantation: Cellular and molecular mechanisms
Dar, W. A., Sullivan, E., Bynon, J. S., Eltzschig, H. K., & Ju, C. (2019) · Liver International · doi:10.1111/liv.14091 · Cited by 401 · see citing works
Spermidine induces autophagy by inhibiting the acetyltransferase EP300
Pietrocola, F., Lachkar, S., Enot, D. P., Niso-Santano, M., Bravo-San Pedro, J. M., Sica, V, Izzo, V, Maiuri, M. C., Madeo, F., Mariño, G., et al. (2015) · Cell Death & Differentiation · doi:10.1038/cdd.2014.215 · Cited by 357 · see citing works
An ALOX12–12-HETE–GPR31 signaling axis is a key mediator of hepatic ischemia–reperfusion injury
Zhang, X., Cheng, X., Yan, Z., Fang, J., Wang, X., Wang, W., Liu, Z., Shen, L., Zhang, P., Wang, P., et al. (2017) · Nature Medicine · doi:10.1038/nm.4451 · Cited by 245 · see citing works
Self-citationHepatic Ischemia/Reperfusion: Mechanisms of Tissue Injury, Repair, and Regeneration
Konishi, T., & Lentsch, A. B. (2017) · Gene Expression · doi:10.3727/105221617x15042750874156 · Cited by 239 · see citing works
Autophagy in Cardiovascular Aging
Abdellatif, M., Sedej, S., Carmona-Gutierrez, D., Madeo, F., & Kroemer, G. (2018) · Circulation Research · doi:10.1161/circresaha.118.312208 · Cited by 239 · see citing works
Yue, F., Li, W., Zou, J., Jiang, X., Xu, G., Huang, H. W., & Liu, L. (2017) · Cancer Research · doi:10.1158/0008-5472.can-16-3462 · Cited by 176 · see citing works
Yang, Q., Zheng, C., Cao, J., Cao, G., Shou, P., Lin, L., Velletri, T., Jiang, M., Chen, Q., Han, Y., et al. (2016) · Cell Death and Differentiation · doi:10.1038/cdd.2016.71 · Cited by 161 · see citing works
Nakazato, P. C. G., Victorino, J. P., Fina, C. F., et al. (2018) · Acta Cirúrgica Brasileira · doi:10.1590/s0102-865020180080000008 · Cited by 61 · see citing works
Zhu, J., Lu, T., Yue, S., Shen, X., Gao, F., Busuttil, R. W., Kupiec‐Weglinski, J. W., Xia, Q., & Zhai, Y. (2014) · Transplantation · doi:10.1097/tp.0000000000000476 · Cited by 60 · see citing works
Zaki, A. M., El-Tanbouly, D. M., Abdelsalam, R. M., & Zaki, H. F. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.07.004 · Cited by 40 · see citing works
Wang, Y., Wen, X., Hao, D., Zhou, M., Li, X., He, G., & Jiang, X. L. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.108775 · Cited by 37 · see citing works
Abdulrahman, R. M., Boon, M. R., Sips, H. C. M., Guigas, B., Rensen, P. C. N., Smit, J. W. A., & Hovens, G. C. (2013) · Thyroid · doi:10.1089/thy.2013.0041 · Cited by 35 · see citing works
Yang, J., Wang, Y., Sui, M., Liu, F., Fu, Z., & Wang, Q.-X. (2015) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2015.10.080 · Cited by 27 · see citing works
Self-citationLiu, A., & Fang, H. (2019) · Journal of Investigative Surgery · doi:10.1080/08941939.2019.1578443 · Cited by 6 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The mitochondrial permeability transition: Nexus of aging, disease and longevity
Rottenberg, H., & Hoek, J. B. (2021) · Cells · doi:10.3390/cells10010079 · Cited by 94 · see citing works
- Authors
- Liu, H., Dong, J., Song, S., Zhao, Y., Wang, J., Fu, Z., & Yang, J.
- Affiliations
- Second Military Medical University (CN)
- Corresponding author
- Fu, Zhiren
- Yang, Jinghui
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2019-11
- Volume
- 519
- Issue
- 2
- Pages
- 227-233
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2972303616
- Cited by
- 38
- References
- 23
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 5 · 2023: 6 · 2022: 9 · 2021: 4 · 2020: 7
- FWCI
- 3.84
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- spermidine, liver ischaemia-reperfusion injury, autophagy, apoptosis, hepatoprotection, inflammatory cytokines, autophagosome formation
- MeSH terms
- Autophagy-Related Protein-1 Homolog, Animals, Autophagy, Liver, Male, Mice, Inbred C57BL, Spermidine, Signal Transduction, Reperfusion Injury, Mice, AMP-Activated Protein Kinases, TOR Serine-Threonine Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
