AMPKα2 exerts its anti-inflammatory effects through PARP-1 and Bcl-6
Open accessAbstract
B-cell lymphoma-6 protein (Bcl-6) is a corepressor for inflammatory mediators such as vascular cell adhesion molecule-1 and monocyte chemotactic protein-1 and -3, which function to recruit monocytes to vascular endothelial cells upon inflammation. Poly [ADP ribose] polymerase 1 (PARP-1) is proinflammatory, in part through its binding at the Bcl-6 intron 1 to suppress Bcl-6 expression. We investigated the mechanisms by which PARP-1 dissociates from the Bcl-6 intron 1, ultimately leading to attenuation of endothelial inflammation. Analysis of the PARP-1 primary sequence suggested that phosphorylation of PARP-1 Serine 177 (Ser-177) by AMP-activated protein kinase (AMPK) is responsible for the induction of Bcl-6. Our results show that AMPK activation with treatment of 5-aminoimidazole-4-carboxamide ribonucleotide, metformin, or pulsatile shear stress induces PARP-1 dissociation from the Bcl-6 intron 1, increases Bcl-6 expression, and inhibits expression of inflammatory mediators. Conversely, AMPKα suppression or knockdown produces the opposite effects. The results demonstrate an anti-infamatory pathway linking AMPK, PARP-1, and Bcl-6 in endothelial cells.
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?
AMPK exerted its anti-inflammatory roles on the vasculature partially via the inhibition of adhesion molecules and chemoattractants by regulating signal transducer and activator of transcription 3, of nuclear factor kappa B, and p300 pathways.
“Indeed, studies have uncovered that AMPK exerted its anti-inflammatory roles on the vasculature partially via the inhibition of adhesion molecules and chemoattractants [248,249,252,253] by regulating signal transducer and activator of transcription 3, of nuclear factor kappa B, and p300 pathways [254,255,256].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [254]
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
1 retracted
Liu, C., Liang, B., Wang, Q., Wu, J., & Zou, M. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.102491 · Cited by 82 · see citing works
RetractedPARP inhibition: PARP1 and beyond
Rouleau, M., Patel, A., Hendzel, M. J., Kaufmann, S. H., & Poirier, G. G. (2010) · Nature Reviews Cancer · doi:10.1038/nrc2812 · Cited by 1,298 · see citing works
Anti-TNFα Therapy of Rheumatoid Arthritis: What Have We Learned?
Feldmann, M., & Maini, R. N. (2001) · Annual Review of Immunology · doi:10.1146/annurev.immunol.19.1.163 · Cited by 1,252 · see citing works
Marui, N., Offermann, M. K., Swerlick, R., Kunsch, C., Rosen, C. A., Ahmad, M., Alexander, R. W., & Medford, R. M. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116778 · Cited by 1,072 · see citing works
Salminen, A., Hyttinen, J. M. T., & Kaarniranta, K. (2011) · Journal of Molecular Medicine · doi:10.1007/s00109-011-0748-0 · Cited by 866 · see citing works
Lack of Interleukin-1β Decreases the Severity of Atherosclerosis in ApoE-Deficient Mice
Kirii, H., Niwa, T., Yamada, Y., Wada, H., Saito, K., Iwakura, Y., Asano, M., Moriwaki, H., & Seishima, M. (2003) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000064374.15232.c3 · Cited by 748 · see citing works
On PAR with PARP: cellular stress signaling through poly(ADP-ribose) and PARP-1Preprint
Luo, X., & Kraus, W. L. (2012) · Genes & Development · doi:10.1101/gad.183509.111 · Cited by 725 · see citing works
Hawley, S. A., Gadalla, A. E., Olsen, G. S., & Hardie, D. G. (2002) · Diabetes · doi:10.2337/diabetes.51.8.2420 · Cited by 696 · see citing works
Diabetic endothelial dysfunction: the role of poly(ADP-ribose) polymerase activation
Soriano, F. G., Virág, L., Jagtap, P. G., Szabó, É., Mabley, J. G., Liaudet, L., Marton, A., Hoyt, D. G., Murthy, K. G. K., Salzman, A. L., et al. (2001) · Nature Medicine · doi:10.1038/83241 · Cited by 602 · see citing works
Oliver, F. J., Murcia, J. M., Nacci, C., Decker, P., Andriantsitohaina, R., Muller, S., de la Rubia, G., Stoclet, J., & de MURCIA, G. (1999) · The EMBO Journal · doi:10.1093/emboj/18.16.4446 · Cited by 583 · see citing works
Transcriptional Repression of Atherogenic Inflammation: Modulation by PPARδ
Lee, C., Chawla, A., Urbiztondo, N., Liao, D., Boisvert, W. A., & Evans, R. M. (2003) · Science · doi:10.1126/science.1087344 · Cited by 582 · see citing works
Łoś, M., Mozoluk, M., Ferrari, D., Stępczyńska, A., Stroh, C., Renz, A., Herceg, Z., Wang, Z., & Schulze‐Osthoff, K. (2002) · Molecular Biology of the Cell · doi:10.1091/mbc.01-05-0272 · Cited by 505 · see citing works
Ordás, Í., Mould, D. R., Feagan, B. G., & Sandborn, W. J. (2012) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2011.328 · Cited by 497 · see citing works
BCoR, a novel corepressor involved in BCL-6 repressionPreprint
Huynh, K. D., Fischle, W., Verdin, E. M., & Bardwell, V. J. (2000) · Genes & Development · doi:10.1101/gad.14.14.1810 · Cited by 475 · see citing works
Hassa, P. O., & Hottiger, M. O. (2002) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-002-8527-2 · Cited by 428 · see citing works
The BCL-6 POZ domain and other POZ domains interact with the co-repressors N-CoR and SMRT
Huynh, K. D., & Bardwell, V. J. (1998) · Oncogene · doi:10.1038/sj.onc.1202197 · Cited by 311 · see citing works
Wang, S., Zhang, M., Liang, B., Xu, J., Xie, Z., Liu, C., Viollet, B., Yan, D., & Zou, M.-H. (2010) · Circulation Research · doi:10.1161/circresaha.109.212530 · Cited by 296 · see citing works
Statins Activate AMP-Activated Protein Kinase In Vitro and In Vivo
Sun, W., Lee, T., Zhu, M., Gu, C., Wang, Y., Zhu, Y., & Shyy, J. Y.-J. (2006) · Circulation · doi:10.1161/circulationaha.106.630194 · Cited by 264 · see citing works
Self-citationPARP-1 is involved in autophagy induced by DNA damage
Muñoz‐Gámez, J. A., Rodríguez-Vargas, J. M., Quiles, R., Aguilar‐Quesada, R., Martín‐Oliva, D., de MURCIA, G., Murcia, J. M., Almendros-Ruiz, A., de Almodóvar, J. M. R., & Oliver, F. J. (2009) · Autophagy · doi:10.4161/auto.5.1.7272 · Cited by 248 · see citing works
Tang, C., Chiu, Y., Tan, T., Yang, R., & Fu, W. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.8.5483 · Cited by 244 · see citing works
Zhang, Y., Lee, T.-S., Kolb, E. M., Sun, K., Lu, X., Sladek, F. M., Kassab, G. S., Garland, T., & Shyy, J. Y.-J. (2006) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000221230.08596.98 · Cited by 212 · cited 1× · see citing works
“In particular, pulsatile flow (PS) activates AMPK (25) and is associated with anti-inflammatory effects (6– 9).”
BackgroundPPARδ-mediated antiinflammatory mechanisms inhibit angiotensin II-accelerated atherosclerosis
Takata, Y., Liu, J., Yin, F., Collins, A. R., Lyon, C. J., Lee, C., Atkins, A. R., Downes, M., Barish, G. D., Evans, R. M., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708647105 · Cited by 211 · see citing works
Nagata, D., Takeda, R., Sata, M., Satonaka, H., Suzuki, E., Nagano, T., & Hirata, Y. (2004) · Circulation · doi:10.1161/01.cir.0000136025.96811.76 · Cited by 198 · see citing works
BCL-6 regulates chemokine gene transcription in macrophages
Toney, L. M., Cattoretti, G., Graf, J. A., Merghoub, T., Pandolfi, P. P., Dalla‐Favera, R., Ye, B. H., & Dent, A. L. (2000) · Nature Immunology · doi:10.1038/79749 · Cited by 171 · see citing works
Suppression of Pro-inflammatory Adhesion Molecules by PPAR-δ in Human Vascular Endothelial Cells
Fan, Y., Wang, Y., Tang, Z., Zhang, H., Qin, X., Zhu, Y., Guan, Y., Wang, X., Staels, B., Chien, S., et al. (2007) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.107.149815 · Cited by 163 · see citing works
Self-citationCaballero, A. E., Delgado, A., Aguilar-Salinas, C. A., Herrera, A. N., Castillo, J. L., Cabrera, T., Gomez-Perez, F. J., & Rull, J. A. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0019 · Cited by 151 · see citing works
Schulz, E., Dopheide, J. F., Schuhmacher, S., Thomas, S. R., Chen, K., Daiber, A., Wenzel, P., Münzel, T. F., & Keaney, J. F. (2008) · Circulation · doi:10.1161/circulationaha.108.784289 · Cited by 150 · see citing works
Wang, Q., Zhang, M., Liang, B., Shirwany, N. A., Zhu, Y., & Zou, M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025436 · Cited by 144 · see citing works
Zhang, Y., Qiu, J., Wang, X., Zhang, Y., & Xia, M. (2011) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.111.237453 · Cited by 121 · see citing works
Mathews, M. T., & Berk, B. C. (2008) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.107.156406 · Cited by 120 · see citing works
Li, D., Wang, D., Wang, Y., Ling, W., Feng, X., & Xia, M. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.159772 · Cited by 115 · 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-citationNerstedt, A., Johansson, A., Andersson, C. X., Cansby, E., Smith, U., & Mahlapuu, M. (2010) · Diabetologia · doi:10.1007/s00125-010-1856-z · Cited by 106 · see citing works
Kashima, L., Idogawa, M., Mita, H., Shitashige, M., Yamada, T., Ogi, K., Suzuki, H., Toyota, M., Ariga, H., Sasaki, Y., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.321828 · Cited by 103 · see citing works
Murao, K., Ohyama, T., Imachi, H., Ishida, T., Cao, W. M., Namihira, H., Sato, M., Wong, N. C. W., & Takahara, J. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3497 · Cited by 99 · see citing works
Liu, C., Liu, T., Kuo, L., et al. (2008) · The Journal of Pathology · doi:10.1002/path.2306 · Cited by 77 · see citing works
Metformin prevents endotoxin-induced liver injury after partial hepatectomy
Bergheim, I., Luyendyk, J. P., Steele, C., Russell, G. K., Guo, L., Roth, R. A., & Arteel, G. E. (2006) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.105.092122 · Cited by 75 · see citing works
PARP1 is required for adhesion molecule expression in atherogenesis
von Lukowicz, T., Hassa, P. O., Lohmann, C., Borén, J., Braunersreuther, V., Mach, F., Odermatt, B. F., Gersbach, M., Camici, G. G., Stähli, B. E., et al. (2007) · Cardiovascular Research · doi:10.1093/cvr/cvm110 · Cited by 74 · see citing works
Rácz, B., Hantó, K., Tapodi, A., Solti, I., Kálmán, N., Jakus, P., Kovács, K., Debreceni, B., Gallyas, F., & Sümegi, B. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.09.026 · Cited by 63 · see citing works
Ewart, M.-A., Kohlhaas, C. F., & Salt, I. P. (2008) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.108.175919 · Cited by 57 · see citing works
Donato, A. J., Henson, G. D., Morgan, R. G., Enz, R. A., Walker, A. E., & Lesniewski, L. A. (2012) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00271.2012 · Cited by 50 · see citing works
Shimazaki, T., Arsenijévic, Y., Ryan, A. K., Rosenfeld, M. G., & Weiss, S. (1999) · The EMBO Journal · doi:10.1093/emboj/18.2.444 · Cited by 49 · see citing works
Ambrose, H. E., Papadopoulou, V., Beswick, R. W., & Wagner, S. D. (2007) · Oncogene · doi:10.1038/sj.onc.1210434 · Cited by 41 · see citing works
BCL6 represses NFκB activity in diffuse large B‐cell lymphomas
Pérez‐Rosado, A., Artiga, M. J., Vargiu, P., Sánchez‐Aguilera, A., Alvarez, A. M., & Piris, M. A. (2008) · The Journal of Pathology · doi:10.1002/path.2279 · Cited by 41 · see citing works
Condensin I Recruitment to Base Damage-Enriched DNA Lesions Is Modulated by PARP1
Kong, X., Stephens, J. P., Ball, A. R., Heale, J. T., Newkirk, D. A., Berns, M. W., & Yokomori, K. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023548 · Cited by 35 · see citing works
Zhu, H., Jiang, Z., Lei, P., et al. (2011) · Kidney & Blood Pressure Research · doi:10.1159/000327344 · Cited by 7 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Orecchioni, M., Ghosheh, Y., Pramod, A. B., & Ley, K. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01084 · Cited by 2,063 · see citing works
AMPK, Mitochondrial Function, and Cardiovascular Disease
Wu, S., & Zou, M.-H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21144987 · Cited by 286 · see citing works
Marin, T. L., Gongol, B., Zhang, F., Martin, M., Johnson, D. A., Xiao, H., Wang, Y., Subramaniam, S., Chien, S., & Shyy, J. Y.-J. (2017) · Science Signaling · doi:10.1126/scisignal.aaf7478 · Cited by 257 · see citing works
Self-citationEndothelial Function and Dysfunction: Impact of Metformin
Nafisa, A., Gray, S. G., Cao, Y., Wang, T., Xu, S., Wattoo, F. H., Barras, M., Cohen, N., Kamato, D., & Little, P. J. (2018) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.07.007 · Cited by 128 · see citing works
Can Metformin Exert as an Active Drug on Endothelial Dysfunction in Diabetic Subjects
Salvatore, T., Pafundi, P. C., Galiero, R., Rinaldi, L., Caturano, A., Vetrano, E., Aprea, C., Albanese, G., Di Martino, A., Ricozzi, C., et al. (2020) · Biomedicines · doi:10.3390/biomedicines9010003 · Cited by 97 · see citing works
- Authors
- Gongol, B., Marin, T., Peng, I.-C., Woo, B., Martin, M., King, S., Sun, W., Johnson, D. A., Chien, S., & Shyy, J. Y.-J.
- Affiliations
- University of California, Riverside (US)
- Biochemistry and Molecular Biology Graduate Program, and
- University of California San Diego (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-02-04
- Volume
- 110
- Issue
- 8
- Pages
- 3161-3166
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3581905
- OpenAlex
- W1986810494
- Cited by
- 61
- References
- 46
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 7 · 2022: 3 · 2021: 4 · 2020: 4 · 2019: 7 · 2018: 6 · 2017: 4 · 2016: 9 · 2015: 3 · 2014: 6 · 2013: 1
- FWCI
- 2.83
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL106579, HL‐080518, R01HL089940, R01HL080518, HL93731, R01HL108735, HL108735, R21HL093731, HL89940)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- AMPKα2, PARP1, BCL6, anti-inflammatory signaling, endothelial inflammation, vascular endothelial growth factor, VCAM-1, MCP-1, MCP-3, monocyte recruitment, metformin, pulsatile shear stress, vascular inflammation
- MeSH terms
- Poly (ADP-Ribose) Polymerase-1, Animals, Cells, Cultured, Introns, Phosphorylation, Poly(ADP-ribose) Polymerases, Transcription, Genetic, Transcriptional Activation, Mice, Proto-Oncogene Proteins c-bcl-6, 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
