RETRACTED: Redox Regulation of the AMP-Activated Protein Kinase
Open accessAbstract
Redox state is a critical determinant of cell function, and any major imbalances can cause severe damage or death. Objectives: The aim of this study is to determine if AMP-activated protein kinase (AMPK), a cellular energy sensor, is activated by oxidants generated by Berberine in endothelial cells (EC). Methods: Bovine aortic endothelial cells (BAEC) were exposed to Berberine. AMPK activity and reactive oxygen species were monitored after the incubation. Results: In BAEC, Berberine caused a dose- and time-dependent increase in the phosphorylation of AMPK at Thr172 and acetyl CoA carboxylase (ACC) at Ser79, a well characterized downstream target of AMPK. Concomitantly, Berberine increased peroxynitrite, a potent oxidant formed by simultaneous generation of superoxide and nitric oxide. Pre-incubation of BAEC with anti-oxidants markedly attenuated Berberine-enhanced phosphorylation of both AMPK and ACC. Consistently, adenoviral expression of superoxide dismutase and pretreatment of L-N G -Nitroarginine methyl ester (L-NAME; a non-selective NOS inhibitor) blunted Berberine-induced phosphorylation of AMPK. Furthermore, mitochondria-targeted tempol (mito-tempol) pretreatment or expression of uncoupling protein attenuated AMPK activation caused by Berberine. Depletion of mitochondria abolished the effects of Berberine on AMPK in EC. Finally, Berberine significantly increased the phosphorylation of LKB1 at Ser307 and gene silencing of LKB1 attenuated Berberine-enhanced AMPK Thr172 phosphorylation in BAEC. Conclusion: Our results suggest that mitochondria-derived superoxide anions and peroxynitrite are required for Berberine-induced AMPK activation in endothelial cells.
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AMPK is responsive to imbalanced redox status.
“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 [43]
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7 retracted
Activation of the AMP-activated Protein Kinase by the Anti-diabetic Drug Metformin in Vivo
Zou, M., Kirkpatrick, S. S., Davis, B. J., Nelson, J. S., Wiles, W. G., Schlattner, U., Neumann, D., Brownlee, M., Freeman, M. B., & Goldman, M. H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m404421200 · Cited by 471 · see citing works
Self-citationRetractedActivation of Protein Phosphatase 2A by Palmitate Inhibits AMP-activated Protein Kinase
Wu, Y., Song, P., Xu, J., Zhang, M., & Zou, M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m608310200 · Cited by 272 · see citing works
Self-citationRetractedZhang, J., Xie, Z., Dong, Y., Wang, S., Liu, C., & Zou, M. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m802578200 · Cited by 114 · see citing works
Self-citationRetractedAn, Z., Wang, H., Song, P., Zhang, M., Geng, X., & Zou, M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m703701200 · Cited by 97 · see citing works
Self-citationRetractedChoi, H. C., Song, P., Xie, Z., Wu, Y., Xu, J., Zhang, M., Dong, Y., Wang, S., Lau, K., & Zou, M. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m803020200 · Cited by 85 · see citing works
Self-citationRetractedSong, P., Xie, Z., Wu, Y., Xu, J., Dong, Y., & Zou, M. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m708208200 · Cited by 70 · see citing works
Self-citationRetractedSong, P., Zhang, M., Wang, S., Xu, J., Choi, H. C., & Zou, M. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.012583 · Cited by 46 · see citing works
Self-citationRetractedRole of AMP-Activated Protein Kinase in Mechanism of Metformin Action
Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13505 · Cited by 5,652 · see citing works
Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase
Minokoshi, Y., Kim, Y.-B., Peroni, O. D., Fryer, L. G. D., Müller, C., Carling, D., & Kahn, B. B. (2002) · Nature · doi:10.1038/415339a · Cited by 2,053 · see citing works
Active and Inactive Protein Kinases: Structural Basis for Regulation
Johnson, L. N., Noble, M. E. M., & Owen, D. J. (1996) · Cell · doi:10.1016/s0092-8674(00)81092-2 · Cited by 1,396 · see citing works
AMP-activated protein kinase signaling in metabolic regulation
Long, Y. C. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29044 · Cited by 1,097 · see citing works
Lee, Y. S., Kim, W. S., Kim, K. H., Yoon, M. J., Cho, H. J., Shen, Y., Ye, J.-M., Lee, C. H., Oh, W. K., Kim, C. T., et al. (2006) · Diabetes · doi:10.2337/db06-0006 · Cited by 1,054 · see citing works
Zang, M., Xu, S., Maitland, K. A., Zuccollo, A., Hou, X., Jiang, B., Wierzbicki, M., Verbeuren, T. J., & Cohen, R. A. (2006) · Diabetes · doi:10.2337/db05-1188 · Cited by 663 · see citing works
Turner, N., Li, J.-Y., Gosby, A., To, S. W. C., Cheng, Z., Miyoshi, H., Taketo, M. M., Cooney, G. J., Kraegen, E. W., James, D. E., et al. (2008) · Diabetes · doi:10.2337/db07-1552 · Cited by 535 · see citing works
AMPK: A Key Sensor of Fuel and Energy Status in Skeletal Muscle
Hardie, D. G., & Sakamoto, K. (2006) · Physiology · doi:10.1152/physiol.00044.2005 · Cited by 519 · see citing works
Kukidome, D., Nishikawa, T., Sonoda, K., Imoto, K., Fujisawa, K., Yano, M., Motoshima, H., Taguchi, T., Matsumura, T., & Araki, E. (2006) · Diabetes · doi:10.2337/diabetes.55.01.06.db05-0943 · Cited by 504 · see citing works
AMP-activated protein kinase, super metabolic regulator
Kemp, B. E., Stapleton, D., Campbell, D. J., Chen, Z.-P., Murthy, S., Walter, M., Gupta, A., Adams, J. J., Katsis, F., van Denderen, B., et al. (2003) · Biochemical Society Transactions · doi:10.1042/bst0310162 · Cited by 474 · see citing works
Berberine suppresses proinflammatory responses through AMPK activation in macrophages
Jeong, H. W., Hsu, K. C., Lee, J.-W., Ham, M., Huh, J. Y., Shin, H. J., Kim, W. S., & Kim, J. B. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90599.2008 · Cited by 454 · see citing works
Berberine improves glucose metabolism through induction of glycolysis
Yin, J., Gao, Z., Liu, D., Liu, Z., & Ye, J. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00211.2007 · Cited by 411 · see citing works
Mantena, S. K., Sharma, S. D., & Katiyar, S. K. (2006) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-05-0448 · Cited by 353 · see citing works
Brusq, J.-M. G., Ancellin, N., Grondin, P., Guillard, R., Martin, S., Saintillan, Y., & Issandou, M. (2006) · Journal of Lipid Research · doi:10.1194/jlr.m600020-jlr200 · Cited by 344 · see citing works
Redox Mechanisms in Blood Vessels
Mueller, C. F. H., Laude, K. M., McNally, J. S., & Harrison, D. G. (2004) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000149143.04821.eb · Cited by 342 · see citing works
Nagata, D., Mogi, M., & Walsh, K. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300643200 · Cited by 331 · see citing works
Kim, W. S., Lee, Y. S., Cha, S. H., Jeong, H. W., Choe, S. S., Lee, M., Oh, G. T., Park, H., Lee, K., Lane, M. D., et al. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90710.2008 · Cited by 239 · see citing works
Ceolotto, G., Gallo, A., Papparella, I., Franco, L., Murphy, E. G., Iori, E., Pagnin, E., Fadini, G. P., Albiero, M., Semplicini, A., et al. (2007) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.107.155762 · Cited by 229 · see citing works
Fernandes, D. C., Wosniak, J., Pescatore, L. A., Bertoline, M. A., Liberman, M., Laurindo, F. R. M., & Santos, C. X. C. (2006) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00188.2006 · Cited by 213 · see citing works
Zhou, L., Deepa, S. S., Etzler, J. C., Ryu, J., Mao, X., Fang, Q., Liu, D. D., Torres, J. M., Jia, W., Lechleiter, J. D., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.028357 · Cited by 212 · see citing works
Cui, G., Qin, X., Zhang, Y., Gong, Z., Ge, B., & Zang, Y. Q. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.012674 · Cited by 197 · see citing works
Zou, M., Hou, X., Shi, C., Nagata, D., Walsh, K., & Cohen, R. A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204512200 · Cited by 189 · see citing works
Self-citationPhysiological role of AMP-activated protein kinase in the heart: graded activation during exercise
Coven, D. L., Hu, X., Cong, L., Bergeron, R., Shulman, G. I., Hardie, D. G., & Young, L. H. (2003) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00171.2003 · Cited by 174 · see citing works
Wang, Y., Huang, Y., Lam, K. S. L., Li, Y., Wong, W. T., Ye, H., Lau, C., Vanhoutte, P. M., & Xu, A. (2009) · Cardiovascular Research · doi:10.1093/cvr/cvp078 · Cited by 165 · see citing works
Pereira, G. C., Branco, A. F., Matos, J. A. C., Pereira, S. L., Parke, D., Perkins, E. L., Serafim, T. L., Sardão, V. A., Santos, M. S., Moreno, A. J. M., et al. (2007) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.107.128017 · Cited by 152 · see citing works
McCrimmon, R. J., Fan, X., Ding, Y., Zhu, W., Jacob, R. J., & Sherwin, R. S. (2004) · Diabetes · doi:10.2337/diabetes.53.8.1953 · Cited by 148 · see citing works
AMP-activated protein kinase promotes the differentiation of endothelial progenitor cells
Li, X., Han, Y., Pang, W., Li, C., Xie, X., Shyy, J. Y.-J., & Zhu, Y. (2008) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.108.172452 · Cited by 113 · see citing works
Self-citationThe good, the bad and the ugly in oxygen-sensing: ROS, cytochromes and prolyl-hydroxylases
Acker, T., Fandrey, J., & Acker, H. (2006) · Cardiovascular Research · doi:10.1016/j.cardiores.2006.04.008 · Cited by 112 · see citing works
Xie, Z., Dong, Y., Zhang, J., Scholz, R., Neumann, D., & Zou, M. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.01417-08 · Cited by 98 · see citing works
Self-citationZhang, M., Dong, Y., Xu, J., Xie, Z., Wu, Y., Song, P., Guzman, M., Wu, J., & Zou, M.-H. (2008) · Circulation Research · doi:10.1161/circresaha.107.163253 · Cited by 82 · see citing works
Self-citationBerberine inhibits human neuroblastoma cell growth through induction of p53-dependent apoptosis.
Choi, M. S., Yuk, D. Y., Oh, J. H., Jung, H. Y., Han, S., Moon, D. C., & Hong, J. T. (2008) · PubMed · Cited by 80 · see citing works
Regulation of Rac1 by Simvastatin in Endothelial Cells
Kou, R., Sartoretto, J. L., & Michel, T. M. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m808664200 · Cited by 62 · see citing works
Pereira, C. V., Machado, N. G., & Oliveira, P. J. (2008) · Toxicological Sciences · doi:10.1093/toxsci/kfn131 · Cited by 58 · see citing works
Régulation du métabolisme énergétique par l’AMPK
Foretz, M., Taleux, N., Guigas, B., Horman, S., Beauloye, C., Andréelli, F., Bertrand, L., & Viollet, B. (2006) · médecine/sciences · doi:10.1051/medsci/2006224381 · Cited by 57 · see citing works
Bova, S., Padrini, R., Goldman, W. F., Berman, D. M., & Cargnelli, G. (1992) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)10978-6 · Cited by 56 · see citing works
Letašiová, S., Jantová, S., Miko, M., et al. (2006) · Journal of Pharmacy and Pharmacology · doi:10.1211/jpp.58.2.0015 · Cited by 54 · see citing works
Xiao, X., Su, G., Brown, S. N., Chen, L., Ren, J., & Zhao, P. (2009) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2009.03.011 · Cited by 34 · see citing works
Hypoxia Induces Expression and Activation of AMPK in Rat Dental Pulp Cells
Fukuyama, Y., Ohta, K., Okoshi, R., Suehara, M., Kizaki, H., & Nakagawa, K.-I. (2007) · Journal of Dental Research · doi:10.1177/154405910708600919 · Cited by 31 · see citing works
Foretz, M., Taleux, N., Guigas, B., Horman, S., Beauloye, C., Andréelli, F., Bertrand, L., & Viollet, B. (2006) · Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) · doi:10.7202/012810ar · Cited by 19 · see citing works
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Wu, S., & Zou, M.-H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21144987 · Cited by 286 · see citing works
Self-citationShao, D., Oka, S.-I., Liu, T., Zhai, P., Ago, T., Sciarretta, S., Li, H., & Sadoshima, J. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2013.12.013 · Cited by 252 · see citing works
Gomes, A. P., Duarte, F. V., Nunes, P., Hubbard, B. P., Teodoro, J. S., Varela, A. T., Jones, J. G., Sinclair, D. A., Palmeira, C. M., & Rolo, A. P. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.10.008 · Cited by 159 · see citing works
Jansen, T., Kvandová, M., Daiber, A., Stamm, P., Frenis, K., Schulz, E., Münzel, T., & Kröller-Schön, S. (2020) · Antioxidants · doi:10.3390/antiox9060525 · Cited by 68 · see citing works
Organic cation transporter-mediated drug-drug interaction potential between berberine and metformin
Kwon, M., Choi, Y. A., Choi, M.-K., & Song, I.-S. (2015) · Archives of Pharmacal Research · doi:10.1007/s12272-014-0510-6 · Cited by 56 · see citing works
- Authors
- Han, Y., Wang, Q., Song, P., Zhu, Y., & Zou, M.-H.
- Affiliations
- Peking University (CN)
- University of Oklahoma Health Sciences Center (US)
- Corresponding author
- Zou, Ming-Hui
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-11-05
- Volume
- 5
- Issue
- 11
- Pages
- e15420
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2974634
- OpenAlex
- W2023654927
- Cited by
- 71
- References
- 46
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 2 · 2021: 6 · 2020: 3 · 2019: 4 · 2018: 2 · 2017: 5 · 2016: 7 · 2015: 8 · 2014: 7 · 2013: 4 · 2012: 9
- FWCI
- 2.61
- Type
- journal article
- Language
- en
- Status
- Retracted
- Update notices
- retraction (2026-08-12)
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- American Diabetes Association (HL105157, HL080499, HL074399, HL079584, HL096032, HL089920)
- American Heart Association
- University of Oklahoma
- National Natural Science Foundation of China
- National Institutes of Health (HL080499, HL074399)
- National Heart, Lung, and Blood Institute (HL-105157, R01HL105157, HL 079584, R01HL079584, HL-080499, HL096032, HL074399, R01HL074399, R01HL080499, HL-089920, R01HL110488, R01HL089920, R01HL096032)
- 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
- Health Sciences › Medicine › Pharmacology › Berberine and alkaloids research
- Keywords
- AMPK, redox regulation, berberine, endothelial cells, reactive oxygen species, peroxynitrite, superoxide, acetyl-CoA carboxylase, LKB1, mitochondria, uncoupling proteins, superoxide dismutase, nitric oxide synthase inhibition, tempol
- MeSH terms
- Acetyl-CoA Carboxylase, Adenosine Monophosphate, Adenosine Triphosphate, Animals, Antioxidants, Berberine, Cattle, Cell Line, Cyclic N-Oxides, Electron Transport Complex IV, Enzyme Activation, Humans, Mitochondria, Oxidation-Reduction, Phosphorylation, Serine, Spin Labels, Superoxides, Superoxide Dismutase, Threonine, Time Factors, Blotting, Western, Reverse Transcriptase Polymerase Chain Reaction, Peroxynitrous Acid, Endothelial Cells, AMP-Activated Protein Kinases
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