The DOI matches its Crossref record; 69 of the 69 references it cites were found in a registry or an index.
Exposure to hydrogen peroxide induces oxidation and activation of AMP-activated protein kinase
Open accessAbstract
Although metabolic conditions associated with an increased AMP/ATP ratio are primary factors in the activation of 5'-adenosine monophosphate-activated protein kinase (AMPK), a number of recent studies have shown that increased intracellular levels of reactive oxygen species can stimulate AMPK activity, even without a decrease in cellular levels of ATP. We found that exposure of recombinant AMPKαβγ complex or HEK 293 cells to H(2)O(2) was associated with increased kinase activity and also resulted in oxidative modification of AMPK, including S-glutathionylation of the AMPKα and AMPKβ subunits. In experiments using C-terminal truncation mutants of AMPKα (amino acids 1-312), we found that mutation of cysteine 299 to alanine diminished the ability of H(2)O(2) to induce kinase activation, and mutation of cysteine 304 to alanine totally abrogated the enhancing effect of H(2)O(2) on kinase activity. Similar to the results obtained with H(2)O(2)-treated HEK 293 cells, activation and S-glutathionylation of the AMPKα subunit were present in the lungs of acatalasemic mice or mice treated with the catalase inhibitor aminotriazole, conditions in which intracellular steady state levels of H(2)O(2) are increased. These results demonstrate that physiologically relevant concentrations of H(2)O(2) can activate AMPK through oxidative modification of the AMPKα subunit. The present findings also imply that AMPK activation, in addition to being a response to alterations in intracellular metabolic pathways, is directly influenced by cellular redox status.
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?
In the citing paper
“Recent lines of evidence have demonstrated AMPK responsiveness to imbalanced redox status, thus bringing new insights into the networks of redox-stimulated signals upstream of AMPK (Table 1) [42,43,44,45,46,47,48,49,50,51].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [48]
In the citing paper
“Exogenous or glucose oxidase-generated hydrogen peroxide induced direct S-glutathionylation on the AMPKα subunit at Cys299 and Cys304, which contributes to AMPK activation [48].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [48]
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
1 retracted
Yun, H., Lee, M., Kim, S. S., & Ha, J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m412994200 · Cited by 147
RetractedReduction in the incidence of type 2 diabetes with lifestyle intervention or metformin
(2002) · New England Journal of Medicine · doi:10.1056/nejmoa012512 · Cited by 19,011
Free Radicals in the Physiological Control of Cell Function
Dröge, W. (2002) · Physiological Reviews · doi:10.1152/physrev.00018.2001 · Cited by 9,855
Mechanisms Underlying Acute Protection From Cardiac Ischemia-Reperfusion Injury
Murphy, E., & Steenbergen, C. (2008) · Physiological Reviews · doi:10.1152/physrev.00024.2007 · Cited by 1,504
Hawley, S. A., Davison, M., Woods, A., Davies, S. P., Beri, R. K., Carling, D., & Hardie, D. G. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.44.27879 · Cited by 1,264
AMP-Activated Protein Kinase in Metabolic Control and Insulin Signaling
Towler, M. C., & Hardie, D. G. (2007) · Circulation Research · doi:10.1161/01.res.0000256090.42690.05 · Cited by 1,262
Schulz, T. J., Zarse, K., Voigt, A., Urban, N., Birringer, M., & Ristow, M. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.08.011 · Cited by 1,209
AMP-activated protein kinase signaling in metabolic regulation
Long, Y. C. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29044 · Cited by 1,125
Shibata, R., Sato, K., Pimentel, D. R., Takemura, Y., Kihara, S., Ohashi, K., Funahashi, T., Ouchi, N., & Walsh, K. (2005) · Nature Medicine · doi:10.1038/nm1295 · Cited by 982
Management of cellular energy by the AMP‐activated protein kinase system
Hardie, D. G., Scott, J. W., Pan, D. A., & Hudson, E. R. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)00560-x · Cited by 868
Flagged first, then by citations
Cited by
Sorted by citations
Items 401–440 of 440
Autophagy in Cellular Stress Responses
Li, J., & Liu, R. (2021) · Springer eBooks · doi:10.1007/978-981-16-0522-2_6
Munansangu, B. S. M. (2018) · Boloka Institutional Repository (North-west University)
Gao, Y. (2017) · Springer eBooks · doi:10.1007/978-981-10-4810-4_18
Schrader, M., (21832286), M. I., & (11103897), J. C. (2022) · Frontiers research topics · doi:10.3389/978-2-83250-838-1
Wang, Y., YiFang, W. A. N. G., ChaoGui, L. U. O., Liu, J., Long, J., & Peng, Y. (2024) · Scientia Sinica Vitae · doi:10.1360/ssv-2023-0170
Bendzunas, G. N., Byrne, D. P., Shrestha, S., Daly, L. A., Oswald, S. O., Katiyar, S., Venkat, A., Yeung, W., Eyers, C. E., Eyers, P. A., et al. (2024) · eLife · doi:10.7554/elife.92536.3
Lee, Y., Yoo, J.-W., Park, C., Lee, H., & Lee, Y.-H. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4868167
Oocyte Mitochondria Link Maternal Environment to Offspring PhenotypePreprint
Cooper, J. F., Nguyen, K., Gates, D. R., Wolfrum, E., Capan, C. D., Lee, H., Williams, D., Okoye, C., Nauta, K. M., Pender, C. L., et al. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4975881
Quadrilatero, J., Rahman, F. A., Thoms, J. P., & Hian‐Cheong, D. J. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-15260-3.00018-1
Oocyte mitochondria link maternal environment to offspring phenotypePreprint
Cooper, J. F., Nguyen, K., Gates, D. R., Wolfrum, E., Capan, C. D., Lee, H., Williams, D., Okoye, C., Nauta, K. M., Sanchez-Avila, X., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.13.653493
Matrella, M. L., Amenta, B., Canino, F., Maffia, A., Cocco, T., Russo, M., & Muscolo, A. (2025) · Foods · doi:10.3390/foods14122012
Kunzová, M., Doleželová, E., Moos, M., Panicucci, B., & Zı́ková, A. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.06.16.659894
Nobarı, H., Parnian-Khajehdizaj, N., & Fleming, A. (2025) · Journal of Functional Foods · doi:10.1016/j.jff.2025.106980
Reactive oxygen species signaling
Sudar-Milovanovic, E. M., Panić, A., Obradovic, M. M., Saba, L., Tiwari, E., Suri, J. S., & Isenović, E. R. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-27333-9.00007-5
LKB1 Spatially Regulates AMPK Activity Coordinate Cellular Oxidative Stress ResponsePreprint
Parks, K., Jhawar, A., Andrikopoulos, A., Winters, D. M., Dean, T. S., Kapelczak, E. D., TeSlaa, T. A., Bouhaddou, M., & Schmitt, D. L. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.11.17.688926 · Cited by 1
The ARK side of the cell: Kinases, metabolism, and therapeutic potential in malignancies
Coliboro-Dannich, V., Farías, A., Espinoza-Francine, L., Concha-Vega, M. A., Almendras-Durán, K., Salazar, A. M., Pincheira, R., & Castro, A. F. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.108056
Comment on: N-butylphthalide alleviates obesity-induced cardiomyopathy by binding directly to Keap1
Xu, Q., & Han, J. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.115966
Constantinou, J. K. (2015) · University of Birmingham Institutional Research Archive (University of Birmingham)
Zhang, Q., Cheng, G., Pan, J., Zielonka, J., Xiong, D., Myers, C. R., Feng, L., Shin, S. S., Kim, Y. H., Bui, D., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12096144
Zhang, Q., Cheng, G., Pan, J., Zielonka, J., Xiong, D., Myers, C. R., Feng, L., Shin, S. S., Kim, Y. H., Bui, D., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12096126
Zhang, Q., Cheng, G., Pan, J., Zielonka, J., Xiong, D., Myers, C. R., Feng, L., Shin, S. S., Kim, Y. H., Bui, D., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12096114
Zhang, Q., Cheng, G., Pan, J., Zielonka, J., Xiong, D., Myers, C. R., Feng, L., Shin, S. S., Kim, Y. H., Bui, D., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12096150
Zhang, Q., Cheng, G., Pan, J., Zielonka, J., Xiong, D., Myers, C. R., Feng, L., Shin, S. S., Kim, Y. H., Bui, D., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12096135
Zhang, Q., Cheng, G., Pan, J., Zielonka, J., Xiong, D., Myers, C. R., Feng, L., Shin, S. S., Kim, Y. H., Bui, D., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12096117
Cancer metabolic rewiring of reactive oxygen species
Kifayat, S., Sanapalli, V., Deshpande, A., Akey, K. S., Baskaran, R., & Sanapalli, B. K. R. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-33459-7.00005-3
Liu, Z., Wu, L., Lu, X., Song, K., & Cao, Y. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.116055
Bashir, R., Ali, T., Kawoosa, S., Jan, I., & Khan, N. A. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-23908-3.00019-8
Kunzová, M., Doleželová, E., Moos, M., Panicucci, B., & Zı́ková, A. (2026) · Communications Biology · doi:10.1038/s42003-026-09933-z
Li, L., Gao, J., Wang, X., Lai, Y., Zhang, Z., Guo, S., & Ding, B. (2026) · World s Poultry Science Journal · doi:10.1080/00439339.2026.2642167 · Cited by 1
Rôles de l’autophagie dans l'homéostasie des cellules souches intestinales
Trentesaux, C. (2018) · theses.fr (ABES) · doi:10.70675/6bad110bz19b1z4cd6z81d0z74d0fb1e27f3
Myeloperoxidase (MPO) mediates LPS-induced mitophagy in murine macrophages through AMPK/ULK1 pathway
Lin, W., Zeng, Y., Li, J., Zhang, X., Wang, Z., Zhao, D., Chen, X., Zhang, Y., & Guo, C. (2026) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2026.04.140
Diabetic retinopathy: shaped by the “hidden hand” of post-translational modifications
Xiao, R., & Zhang, M. (2026) · Molecular Neurodegeneration · doi:10.1186/s13024-026-00973-x
From ROS signaling to redox resistance in exercise and metabolic disease
Louzada, R. A. N. (2026) · Sports Medicine and Health Science · doi:10.1016/j.smhs.2026.07.009
Armartmuntree, N., Kaewlert, W., Aupatham, P., Buakaew, S., Sakonsinsiri, C., Lert-itthiporn, W., Pinlaor, S., & Thanan, R. (2026) · Oxidative Medicine and Cellular Longevity · doi:10.1155/omcl/3094707
AMPK Therapy—A Little Goes A Long Way
CEBALLOS, H. M., Eryun, Z., & Huang, W. (2026) · Cells · doi:10.3390/cells15161503
Rao, J., Li, X., Zhang, Y., Guo, J., Feng, B., Lu, Y., & Ma, X. (2026) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.6c05636
AMPK signaling in cancer: Molecular insights and therapeutic opportunities
Jiang, W., Yan, P., Wang, J., Xue, X., Huang, D., Chen, L., Yang, Y., Inuzuka, H., & Wei, W. (2026) · Cancer Letters · doi:10.1016/j.canlet.2026.218912
The AMPK signaling pathway in cell metabolism and human diseases
Zhang, Z., Gu, Y., He, H., Qiao, S., Shao, Y., 龙先铭, Huang, J., Zhang, L., & Zhou, F. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-02790-6
Metadata
- Authors
- Zmijewski, J. W., Banerjee, S., Bae, H., Friggeri, A., Lazarowski, E. R., & Abraham, E.
- Affiliations
- University of Alabama at Birmingham (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Zmijewski, Jaroslaw W.
- Abraham, Edward
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 285
- Issue
- 43
- Pages
- 33154-33164
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC2963401
- OpenAlex
- W2073966685
- Cited by
- 441
- References
- 68
- Citations by year
- 2026: 21 · 2025: 35 · 2024: 30 · 2023: 22 · 2022: 41 · 2021: 40 · 2020: 45 · 2019: 28 · 2018: 27 · 2017: 27 · 2016: 26 · 2015: 30 · 2014: 22 · 2013: 22 · 2012: 15
- FWCI
- 6.12
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL-62221, P01HL034322, HL 76206, R01HL076206, R01HL062221)
- National Institute of General Medical Sciences (R01GM087748, GM87748)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- AMPK, hydrogen peroxide, oxidative modification, S-glutathionylation, reactive oxygen species, cysteine residues, redox state, catalase inhibition, 3-amino-1,2,4-triazole, AMP/ATP ratio, kinase activation
- MeSH terms
- Adenosine Monophosphate, Adenosine Triphosphate, Amitrole, Animals, Catalase, Cell Line, Enzyme Induction, Enzyme Inhibitors, Glutathione, Humans, Hydrogen Peroxide, Mutation, Oxidation-Reduction, Protein Processing, Post-Translational, Oxidants, Catalytic Domain, Acatalasia, Mice, AMP-Activated Protein 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
