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Islet Cell DNA Is a Target of Inflammatory Attack by Nitric Oxide
Abstract
NO has been identified recently as the prime islet-toxic product of inflammatory macrophages. The adverse effects of IL-1 on isolated islets also have been reported to involve NO. We now show that exposure of an islet cell suspension to the NO donor nitroprusside or to activated macrophages leads to DNA strand breaks. Macrophages did not induce DNA damage in the presence of the NO synthase inhibitor NG-methyl-L-arginine. DNA strand breaks were demonstrated at the level of single cells by a modified nick-translation procedure and confirmed by analysis of DNA fragmentation by gel electrophoresis. DNA strand breaks occurred within 1 h and preceded islet cell lysis. DNA damage could not be prevented by inhibitors of endogenous endonucleases. We conclude that islet cell DNA is an early target of NO action.
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Cited by
Nitric Oxide and Peroxynitrite in Health and Disease
Pacher, P., Beckman, J. S., & Liaudet, L. (2007) · Physiological Reviews · doi:10.1152/physrev.00029.2006 · Cited by 6,390
Nitric oxide synthases: regulation and function
Forstermann, U., & Sessa, W. C. (2012) · European Heart Journal · doi:10.1093/eurheartj/ehr304 · Cited by 4,409
The Therapeutic Potential of Poly(ADP-Ribose) Polymerase Inhibitors
Virág, L., & Szabó, C. (2002) · Pharmacological Reviews · doi:10.1124/pr.54.3.375 · Cited by 1,373
The role of interleukin-1 in the pathogenesis of IDDM
Mandrup-Poulsen, T. (1996) · Diabetologia · doi:10.1007/bf00400649 · Cited by 543
Isoforms of nitric oxide synthase
Förstermann, U., Gath, I., Schwarz, P., Closs, E. I., & Kleinert, H. (1995) · Biochemical Pharmacology · doi:10.1016/0006-2952(95)00181-6 · Cited by 477
Metadata
- Authors
- Fehsel, K., Jalowy, A., Qi, S., Burkart, V., Hartmann, B., & Kolb, H.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 1993-03-01
- Volume
- 42
- Issue
- 3
- Pages
- 496-500
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2159795301
- Cited by
- 188
- References
- 0
- FWCI
- 22.72
- Type
- journal article
- Language
- en
- Open access
- closed
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- Fehsel, K., Jalowy, A., Qi, S., Burkart, V., Hartmann, B., & Kolb, H. (1993). Islet Cell DNA Is a Target of Inflammatory Attack by Nitric Oxide. Diabetes. https://doi.org/10.2337/diab.42.3.496
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
