The DOI matches its Crossref record; 42 of the 43 references it cites were found in a registry or an index.
Absence of receptor interacting protein kinase 3 prevents ethanol-induced liver injury
Open accessAbstract
Hepatocyte cell death via apoptosis and necrosis are major hallmarks of ethanol-induced liver injury. However, inhibition of apoptosis is not sufficient to prevent ethanol-induced hepatocyte injury or inflammation. Because receptor-interacting protein kinase (RIP) 3–mediated necroptosis, a nonapoptotic cell death pathway, is implicated in a variety of pathological conditions, we tested the hypothesis that ethanol-induced liver injury is RIP3-dependent and RIP1-independent. Increased expression of RIP3 was detected in livers of mice after chronic ethanol feeding, as well as in liver biopsies from patients with alcoholic liver disease. Chronic ethanol feeding failed to induce RIP3 in the livers of cytochrome P450 2E1 (CYP2E1)-deficient mice, indicating CYP2E1-mediated ethanol metabolism is critical for RIP3 expression in response to ethanol feeding. Mice lacking RIP3 were protected from ethanol-induced steatosis, hepatocyte injury, and expression of proinflammatory cytokines. In contrast, RIP1 expression in mouse liver remained unchanged following ethanol feeding, and inhibition of RIP1 kinase by necrostatin-1 did not attenuate ethanol-induced hepatocyte injury. Ethanol-induced apoptosis, assessed by terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling–positive nuclei and accumulation of cytokeratin-18 fragments in the liver, was independent of RIP3. Conclusion : CYP2E1-dependent RIP3 expression induces hepatocyte necroptosis during ethanol feeding. Ethanol-induced hepatocyte injury is RIP3-dependent, but independent of RIP1 kinase activity; intervention of this pathway could be targeted as a potential therapeutic strategy.
Overview
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
Verification
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?
The cited source says what the claim attributes to it.
In the citing paper
“Hepatocytes begin to die by lytic forms of cell death including necroptosis(202, 203), pyroptosis(204, 205) and ferroptosis(206), causing damage to surrounding tissue.”
From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [202]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Molecular mechanisms of necroptosis: an ordered cellular explosion
Vandenabeele, P., Galluzzi, L., Vanden Berghe, T., & Kroemer, G. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2970 · Cited by 2,382
Receptor Interacting Protein Kinase-3 Determines Cellular Necrotic Response to TNF-α
He, S., Wang, L., Miao, L., Wang, T., Du, F., Zhao, L., & Wang, X. (2009) · Cell · doi:10.1016/j.cell.2009.05.021 · Cited by 2,214
RIP3, an Energy Metabolism Regulator That Switches TNF-Induced Cell Death from Apoptosis to Necrosis
Zhang, D.-W., Shao, J., Lin, J., Zhang, N., Lu, B.-J., Lin, S.-C., Dong, M.-Q., & Han, J. (2009) · Science · doi:10.1126/science.1172308 · Cited by 1,931
Caspase-8 regulates TNF-α-induced epithelial necroptosis and terminal ileitis
Günther, C., Martini, E., Wittkopf, N., Amann, K., Weigmann, B., Neumann, H., Waldner, M. J., Hedrick, S. Μ., Tenzer, S., Neurath, M. F., et al. (2011) · Nature · doi:10.1038/nature10400 · Cited by 882
Necroptosis as an alternative form of programmed cell death
Christofferson, D. E., & Yuan, J. (2010) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2009.12.003 · Cited by 794
Essential role of tumor necrosis factor α in alcohol-induced liver injury in mice
Yin, M., Wheeler, M. D., Kono, H., Bradford, B. U., Gallucci, R. M., Luster, M. I., & Thurman, R. G. (1999) · Gastroenterology · doi:10.1016/s0016-5085(99)70354-9 · Cited by 699
Apoptosis and Necrosis in the Liver: A Tale of Two Deaths?
Malhi, H., Gores, G. J., & Lemasters, J. J. (2006) · Hepatology · doi:10.1002/hep.21062 · Cited by 694
Mechanisms of Liver Injury. I. TNF-α-induced liver injury: role of IKK, JNK, and ROS pathways
Schwabe, R. F., & Brenner, D. A. (2006) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00422.2005 · Cited by 684
Role of oxidative stress in alcohol-induced liver injury
Cederbaum, A. I., Lu, Y., & Wu, D. (2009) · Archives of Toxicology · doi:10.1007/s00204-009-0432-0 · Cited by 600
High‐mobility group box 1 (HMGB1) protein at the crossroads between innate and adaptive immunity
Bianchi, M. E., & Manfredi, A. A. (2007) · Immunological Reviews · doi:10.1111/j.1600-065x.2007.00574.x · Cited by 600
Flagged first, then by citations
1 of the 43 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Gunther, 2010, Caspase8 regulates TNFalphainduced epithelial necroptosis and terminal ileitis., Nature, 477, 335339
Cited by
Sorted by citations
Necroptosis and its role in inflammation
Pasparakis, M., & Vandenabeele, P. (2015) · Nature · doi:10.1038/nature14191 · Cited by 2,148
Inflammation and aging: signaling pathways and intervention therapies
Li, X., Li, C., Zhang, W., Wang, Y., Qian, P., & Huang, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01502-8 · Cited by 1,443
“Immunostaining with antibodies recognizing phosphorylated mixed lineage kinase domainlike protein (MLKL) serves as a specific marker of necroptosis.(238,239) In addition, immunostaining using antibodies that target phosphorylated MLKL has been identified as a specific marker for necroptosis.”
BackgroundDecoding cell death signals in liver inflammation
Brenner, C., Galluzzi, L., Kepp, O., & Kroemer, G. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2013.03.033 · Cited by 1,022
Necroptosis in development, inflammation and disease
Weinlich, R., Oberst, A., Beere, H. M., & Green, D. R. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.149 · Cited by 1,016
CaMKII is a RIP3 substrate mediating ischemia- and oxidative stress–induced myocardial necroptosis
Zhang, T., Zhang, Y., Cui, M., Jin, L., Wang, Y., Lv, F., Liu, Y., Zheng, W., Shang, H., Zhang, J., et al. (2016) · Nature Medicine · doi:10.1038/nm.4017 · Cited by 790
Metadata
- Authors
- Roychowdhury, S., McMullen, M. R., Pisano, S. G., Liu, X., & Nagy, L. E.
- Affiliations
- Cleveland Clinic (US)
- Corresponding author
- Roychowdhury, Sanjoy
- Venue
- Hepatology
- Published
- 2013-05
- Volume
- 57
- Issue
- 5
- Pages
- 1773-1783
- ISSN
- 0270-9139 (ISSN-L)
- PMC
- PMC3628968
- OpenAlex
- W1993485143
- Cited by
- 304
- References
- 43
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 19 · 2023: 22 · 2022: 24 · 2021: 16 · 2020: 25 · 2019: 29 · 2018: 24 · 2017: 33 · 2016: 33 · 2015: 25 · 2014: 31 · 2013: 11
- FWCI
- 15.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- ABMRF/The Foundation for Alcohol Research
- National Institutes of Health (P20 AA17069)
- National Institute on Alcohol Abuse and Alcoholism (P20 AA17069, R01AA013868, R01AA011975, P20AA017837)
- National Center for Research Resources (UL1RR024989)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- RIPK3, RIPK1, necroptosis, ethanol-induced liver injury, alcoholic liver disease, hepatocyte apoptosis, CYP2E1, necrostatin-1, steatosis, inflammatory cytokines
- MeSH terms
- Adult, Ethanol, Animals, Biopsy, Disease Models, Animal, Female, Humans, Imidazoles, Indoles, Liver, Liver Diseases, Alcoholic, Male, Mice, Inbred C57BL, Middle Aged, Apoptosis, Mice, Knockout, Cytochrome P-450 CYP2E1, Hepatocytes, Mice, Receptor-Interacting Protein Serine-Threonine Kinases, Chemical and Drug Induced Liver Injury
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
