Endonuclease G does not play an obligatory role in poly(ADP-ribose) polymerase-dependent cell death after transient focal cerebral ischemia
Open accessAbstract
Activation of poly(ADP-ribose) polymerase (PARP) and subsequent translocation of apoptosis-inducing factor contribute to caspase-independent neuronal injury from N-methyl-d-aspartate, oxygen-glucose deprivation, and ischemic stroke. Some studies have implicated endonuclease G in the DNA fragmentation associated with caspase-independent cell death. Here, we compared wild-type and endonuclease G null mice to investigate whether endonuclease G plays a role in the PARP-dependent injury that results from transient focal cerebral ischemia. Latex casts did not reveal differences in the cerebral arterial distribution territory or posterior communicating arterial diameter, and the decrease in laser-Doppler flux during middle cerebral artery occlusion was similar in wild-type and endonuclease G null mice. After 90 min of occlusion and 1 day of reperfusion, similar degrees of nuclear translocation of apoptosis-inducing factor and DNA degradation were evident in male wild-type and null mice. At 3 days of reperfusion, infarct volume and neurological deficit scores were not different between male wild-type and endonuclease G null mice or between female wild-type and endonuclease G null mice. These data demonstrate that endonuclease G is not required for the pathogenesis of transient focal ischemia in either male or female mice. Treatment with a PARP inhibitor decreased infarct volume and deficit scores equivalently in male wild-type and endonuclease G null mice, indicating that the injury in endonuclease G null mice remains dependent on PARP. Thus endonuclease G is not obligatory for executing PARP-dependent injury during ischemic stroke.
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?
Parthanatotic DNA fragmentation occurs independently of apoptotic caspases and ENDOG.
“Parthanatotic DNA fragmentation occurs independently of apoptotic caspases and endonuclease G (ENDOG) [670]”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [670]
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
Mediation of Poly(ADP-Ribose) Polymerase-1-Dependent Cell Death by Apoptosis-Inducing Factor
Yu, S.-W., Wang, H., Poitras, M. F., Coombs, C., Bowers, W. J., Federoff, H. J., Poirier, G. G., Dawson, T. M., & Dawson, V. L. (2002) · Science · doi:10.1126/science.1072221 · Cited by 1,826 · see citing works
Self-citationEndonuclease G is an apoptotic DNase when released from mitochondria
Li, L. Y., Luo, X., & Wang, X. (2001) · Nature · doi:10.1038/35083620 · Cited by 1,787 · see citing works
Apoptosis-inducing factor mediates poly(ADP-ribose) (PAR) polymer-induced cell death
Yu, S.-W., Andrabi, S. A., Wang, H., Kim, N. S., Poirier, G. G., Dawson, T. M., & Dawson, V. L. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0606528103 · Cited by 718 · see citing works
Self-citationMitochondrial endonuclease G is important for apoptosis in C. elegans
Parrish, J., Li, L., Klotz, K., Ledwich, D., Wang, X., & Xue, D. (2001) · Nature · doi:10.1038/35083608 · Cited by 427 · see citing works
Mechanisms of AIF-Mediated Apoptotic DNA Degradation in <i>Caenorhabditis elegans</i>
Wang, X., Yang, C., Chai, J., Shi, Y., & Xue, D. (2002) · Science · doi:10.1126/science.1076194 · Cited by 393 · see citing works
Loo, G., Schotte, P., van Gurp, M., Demol, H., Hoorelbeke, B., Gevaert, K., Rodríguez, I., Ruiz-Carrillo, A., Vandekerckhove, J. S., Declercq, W., et al. (2001) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4400944 · Cited by 350 · see citing works
Culmsee, C., Zhu, C., Landshamer, S., Becattini, B., Wagner, E., Pellecchia, M., Blomgren, K., & Plesnila, N. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.2818-05.2005 · Cited by 339 · see citing works
McCullough, L. D., Zeng, Z., Blizzard, K. K., Debchoudhury, I., & Hurn, P. D. (2005) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600059 · Cited by 325 · see citing works
Zhu, C., Xu, F., Wang, X., Shibata, M., Uchiyama, Y., Blomgren, K., & Hagberg, H. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03639.x · Cited by 272 · see citing works
Abdelkarim, G. E., Gertz, K. R., Harms, C., Katchanov, J., Dirnagl, U., Szabó, C., & Endres, M. (2001) · International Journal of Molecular Medicine · doi:10.3892/ijmm.7.3.255 · Cited by 241 · see citing works
Zhang, J., Liu, X., Scherer, D. C., Kaer, L. V., Wang, X., & Xu, M. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.21.12480 · Cited by 183 · see citing works
Self-citationNeuroprotective Effects of Inhibiting Poly(ADP-Ribose) Synthetase on Focal Cerebral Ischemia in Rats
Takahashi, K., Greenberg, J. H., Jackson, P., Maclin, K. M., & Zhang, J. (1997) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199711000-00001 · Cited by 158 · see citing works
Self-citationDifferences in the cerebrovascular anatomy of C57Black/6 and SV129 mice
Maeda, K., Hata, R., & Hossmann, K.-A. (1998) · Neuroreport · doi:10.1097/00001756-199805110-00012 · Cited by 127 · see citing works
Yuan, M., Siegel, C. S., Zeng, Z., Li, J., Liu, F., & McCullough, L. D. (2009) · Experimental Neurology · doi:10.1016/j.expneurol.2009.02.012 · Cited by 123 · see citing works
Generation and Characterization of Endonuclease G Null Mice
Irvine, R. A., Adachi, N., Shibata, D. K., Cassell, G. D., Yu, K., Karanjawala, Z. E., Hsieh, C.-L., & Lieber, M. R. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.1.294-302.2005 · Cited by 111 · see citing works
Endonuclease G is required for early embryogenesis and normal apoptosis in mice
Zhang, J., Dong, M., Li, L. Y., Fan, Y., Pathre, P., Dong, J., Lou, D., Wells, J. M., Olivares–Villagómez, D., Kaer, L. V., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2636393100 · Cited by 100 · see citing works
Self-citationEndoG is dispensable in embryogenesis and apoptosis
David, K. K., Sasaki, M., Yu, S.-W., Dawson, T. M., & Dawson, V. L. (2006) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4401787 · Cited by 96 · see citing works
Self-citationBNIP3 Upregulation and EndoG Translocation in Delayed Neuronal Death in Stroke and in Hypoxia
Zhang, Z., Yang, X., Zhang, S., Ma, X., & Kong, J. (2007) · Stroke · doi:10.1161/strokeaha.106.475129 · Cited by 93 · see citing works
Kauppinen, T. M., Suh, S. W., Berman, A., Hamby, A. M., & Swanson, R. A. (2009) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2009.9 · Cited by 84 · see citing works
Fujimura, M., Morita‐Fujimura, Y., 川瀬, 誠., & Chan, P. H. (1999) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199905000-00003 · Cited by 83 · see citing works
Lee, B. I., Lee, D. J., Cho, K. J., & Kim, G. W. (2005) · Neuroscience Letters · doi:10.1016/j.neulet.2005.05.058 · Cited by 81 · see citing works
Regulation of the human apoptotic DNase/RNase Endonuclease G: involvement of Hsp70 and ATP
Kalinowska, M., Garncarz, W., Pietrowska, M., Garrard, W. T., & Widłak, P. (2005) · APOPTOSIS · doi:10.1007/s10495-005-0410-9 · Cited by 81 · see citing works
EXOG, a novel paralog of Endonuclease G in higher eukaryotes
Cymerman, I. A., Chung, I., Beckmann, B. M., Bujnicki, J. M., & Meiß, G. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkm1169 · Cited by 71 · see citing works
Ishihara, Y., & Shimamoto, N. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m510382200 · Cited by 70 · see citing works
Wang, C., Fang, K., Yang, C., & Tzeng, S. (2009) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22196 · Cited by 69 · see citing works
Nakajima, H., Kakui, N., Ohkuma, K., Ishikawa, M., & Hasegawa, T. (2005) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.104.075465 · Cited by 55 · see citing works
Tanaka, S., Takehashi, M., Iida, S., Kitajima, T., Kamanaka, Y., Stedeford, T. J., Banasik, M., & Ueda, K. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03353.x · Cited by 46 · see citing works
Higgins, G. C., Beart, P. M., & Nagley, P. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-0079-2 · Cited by 45 · see citing works
Li, X., Nemoto, M., Xu, Z., Yu, S.-W., Shimoji, M., Andrabi, S. A., Haince, J.-F., Poirier, G. G., Dawson, T. M., Dawson, V. L., et al. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2006.08.065 · Cited by 42 · see citing works
Self-citationDelayed Tolerance With Repetitive Transient Focal Ischemic Preconditioning in the Mouse
Zhang, J., Yang, Z.-J., Klaus, J. A., Koehler, R. C., & Huang, J. (2008) · Stroke · doi:10.1161/strokeaha.107.497412 · Cited by 38 · see citing works
Self-citationZhao, S., Chen, M., Li, S.-J., Zhang, M.-H., Li, B., Das, M. K., Bean, J. C., Kong, J., Zhu, X., & Gao, T. (2009) · BMC Neuroscience · doi:10.1186/1471-2202-10-113 · Cited by 35 · see citing works
Son, Y., Kook, S., Jang, Y., Shi, X., & Lee, J. (2009) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22332 · Cited by 32 · see citing works
Yu, F., Sugawara, T., Nishi, T., Liu, J., & Chan, P. H. (2006) · Journal of Neurotrauma · doi:10.1089/neu.2006.23.595 · Cited by 23 · see citing works
Nielsen, M., Lambertsen, K. L., Clausen, B. H., Meldgaard, M., Diemer, N. H., Zimmer, J., & Finsen, B. R. (2009) · Experimental Brain Research · doi:10.1007/s00221-008-1665-5 · Cited by 12 · see citing works
Endonuclease G expression in thalamic reticular nucleus after global cerebral ischemia
Nielsen, M., Zimmer, J., & Diemer, N. H. (2008) · Experimental Brain Research · doi:10.1007/s00221-008-1452-3 · Cited by 10 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680 · see citing works
Self-citationCell Biology of Ischemia/Reperfusion Injury
Kalogeris, T. J., Baines, C. P., Krenz, M., & Korthuis, R. J. (2012) · International review of cytology · doi:10.1016/b978-0-12-394309-5.00006-7 · Cited by 2,202 · see citing works
Fundamental Mechanisms of Regulated Cell Death and Implications for Heart Disease
Re, D. P. D., Amgalan, D., Linkermann, A., Liu, Q., & Kitsis, R. N. (2019) · Physiological Reviews · doi:10.1152/physrev.00022.2018 · Cited by 979 · see citing works
Kalogeris, T. J., Baines, C. P., Krenz, M., & Korthuis, R. J. (2016) · Comprehensive physiology · doi:10.1002/cphy.c160006 · Cited by 841 · see citing works
Parthanatos: mitochondrial‐linked mechanisms and therapeutic opportunities
Fatokun, A. A., Dawson, V. L., & Dawson, T. M. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12416 · Cited by 594 · see citing works
Self-citationA nuclease that mediates cell death induced by DNA damage and poly(ADP-ribose) polymerase-1
Wang, Y., An, R., Umanah, G. K., Park, H., Nambiar, K., Eacker, S. M., Kim, B., Bao, L., Harraz, M. M., Chang, C., et al. (2016) · Science · doi:10.1126/science.aad6872 · Cited by 421 · see citing works
Self-citationKalogeris, T. J., Baines, C. P., Krenz, M., & Korthuis, R. J. (2017) · Comprehensive physiology · doi:10.1002/j.2040-4603.2017.tb00741.x · Cited by 115 · see citing works
Liu, L., Li, J., Ke, Y., Zeng, X., Gao, J., Ba, X., & Wang, R. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-04109-w · Cited by 86 · see citing works
Parthanatos in the pathogenesis of nervous system diseases
Wang, X., & Ge, P. (2020) · Neuroscience · doi:10.1016/j.neuroscience.2020.09.049 · Cited by 75 · see citing works
Non-Apoptotic Cell Death Signaling Pathways in Melanoma
Hartman, M. L. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21082980 · Cited by 64 · see citing works
Targeting Parthanatos in Ischemic Stroke
Koehler, R. C., Dawson, V. L., & Dawson, T. M. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.662034 · Cited by 66 · see citing works
Self-citationRevisiting Regulated Cell Death Responses in Viral Infections
Balaya, R. D. A., Prasad, T. S. K., & Kandasamy, R. K. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23137023 · Cited by 59 · see citing works
Augmentation of poly(ADP-ribose) polymerase-dependent neuronal cell death by acidosis
Zhang, J., Li, X., Kwansa, H. E., Kim, Y. T., Yi, L., Hong, G., Andrabi, S. A., Dawson, V. L., Dawson, T. M., Koehler, R. C., et al. (2016) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x16658491 · Cited by 30 · see citing works
Self-citationLi, S., Wang, T., Zhai, L., Ge, K., Zhao, J., Cong, W., & Guo, Y. (2017) · Journal of Molecular Neuroscience · doi:10.1007/s12031-017-1012-z · Cited by 26 · see citing works
Method parameters’ impact on mortality and variability in mouse stroke experiments: a meta-analysis
Ingberg, E., Dock, H., Theodorsson, E., Theodorsson, A., & Ström, J. O. (2016) · Scientific Reports · doi:10.1038/srep21086 · Cited by 25 · see citing works
PGD2 DP1 receptor stimulation following stroke ameliorates cerebral blood flow and outcomes
Ahmad, A. S. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.08.050 · Cited by 20 · see citing works
Cell death classification: A new insight based on molecular mechanisms
Dehghan, S., Kheshtchin, N., Hassannezhad, S., & Soleimani, M. (2023) · Experimental Cell Research · doi:10.1016/j.yexcr.2023.113860 · Cited by 18 · see citing works
Endonucleases and apoptosis in animals
Aleksandrushkina, N. I., & Vanyushin, B. F. (2012) · Biochemistry (Moscow) · doi:10.1134/s0006297912130032 · Cited by 14 · see citing works
Parthanatos: Poly ADP Ribose Polymerase ( PARP )‐Mediated Cell Death
Fatokun, A. A. (2018) · doi:10.1002/9781119432463.ch25 · Cited by 3 · see citing works
Koehler, R. C., Bedirian, K., Chen, M., Shi, Y., Cao, S., Avery, B. D., Karuppagounder, S. S., Akhter, K., Bibic, A., Dawson, V. L., et al. (2025) · Journal of the American Heart Association · doi:10.1161/jaha.124.040914 · Cited by 1 · see citing works
Self-citation
- Authors
- Xu, Z., Zhang, J., David, K. K., Yang, Z.-J., Li, X., Dawson, T. M., Dawson, V. L., & Koehler, R. C.
- Affiliations
- Department of Anesthesiology/Critical Care Medicine,
- Neuroregeneration and Stem Cell Programs, The Institute of Cell Engineering,
- Johns Hopkins University (US)
- Corresponding author
- Koehler, Raymond C.
- ORCID
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 2010-07
- Volume
- 299
- Issue
- 1
- Pages
- R215-R221
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- PMC
- PMC2904146
- OpenAlex
- W2122382169
- Cited by
- 20
- References
- 35
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 4 · 2014: 1 · 2013: 1 · 2012: 2
- FWCI
- 0.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- National Institute of Neurological Disorders and Stroke (NS067525, NS039148, P01NS039148)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Keywords
- endonuclease G, poly(ADP-ribose) polymerase, transient focal cerebral ischemia, ischemic stroke, apoptosis-inducing factor, DNA fragmentation, PARP inhibitors, infarct size, sex differences
- MeSH terms
- Adenosine Diphosphate Ribose, Animals, Ischemic Attack, Transient, Endodeoxyribonucleases, Enzyme Inhibitors, Female, Neurons, Poly Adenosine Diphosphate Ribose, Poly(ADP-ribose) Polymerases, Reperfusion, N-Methylaspartate, Cell Death, Mice, Knockout, Caspases, Infarction, Middle Cerebral Artery, Stroke, D-Aspartic Acid, Apoptosis Inducing Factor, Mice, DNA Fragmentation
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
