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Translocation of Glomerular p47phox and p67phox by Protein Kinase C-β Activation Is Required for Oxidative Stress in Diabetic Nephropathy
Open accessAbstract
Oxidative stress is implicated to play an important role in the development of diabetic vascular complications, including diabetic nephropathy. It is unclear whether oxidative stress is primarily enhanced in the diabetic glomeruli or whether it is merely a consequence of diabetes-induced glomerular injury. To address this issue, we examined diabetic glomeruli to determine whether oxidative stress is enhanced, as well as examined the role of protein kinase C (PKC)-β activation in modulating NADPH oxidase activity. Urinary 8-hydroxydeoxyguanosine excretion and its intense immune-reactive staining in the glomeruli were markedly higher in diabetic than in control rats, and these alterations were ameliorated by a treatment with a selective PKC-β inhibitor, ruboxistaurin (RBX; LY333531) mesylate, without affecting glycemia. NADPH oxidase activity, which was significantly enhanced in diabetic glomeruli and the source of reactive oxygen species (ROS) generation, was also improved by RBX treatment by preventing the membranous translocation of p47phox and p67phox from cytoplasmic fraction without affecting their protein levels. Adenoviral-mediated PKC-β2 overexpression enhanced ROS generation by modulating the membranous translocation of p47phox and p67phox in cultured mesangial cells. We now demonstrate that oxidative stress is primarily enhanced in the diabetic glomeruli due to a PKC-β-dependent activation of NADPH oxidase resulting in ROS generation.
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Cites
Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage
Nishikawa, T., Edelstein, D., Du, X. L., Yamagishi, S.-I., Matsumura, T., Kaneda, Y., Yorek, M. A., Beebe, D., Oates, P. J., Hammes, H.-P., et al. (2000) · Nature · doi:10.1038/35008121 · Cited by 4,277
Role of oxidative stress in diabetic complications: a new perspective on an old paradigm.
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Cited by
Diabetes and Kidney Disease: Role of Oxidative Stress
Jha, J. C., Banal, C., Chow, B. S. M., Cooper, M. E., & Jandeleit-Dahm, K. (2016) · Antioxidants & Redox Signaling · doi:10.1089/ars.2016.6664 · Cited by 660
Rosca, M. G., Mustata, T. G., Kinter, M. T., Ozdemir, A. M., Kern, T. S., Szweda, L. I., Brownlee, M., Monnier, V. M., & Weiss, M. F. (2005) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00415.2004 · Cited by 354
Jha, J. C., Gray, S. P., Barit, D., Okabe, J., El-Osta, A., Namikoshi, T., Thallas-Bonke, V., Wingler, K., Szyndralewiez, C., Heitz, F., et al. (2014) · Journal of the American Society of Nephrology · doi:10.1681/asn.2013070810 · Cited by 352
Fujita, H., Morii, T., Fujishima, H., Sato, T., Shimizu, T., Hosoba, M., Tsukiyama, K., Narita, T., Takahashi, T., Drucker, D. J., et al. (2014) · Kidney International · doi:10.1038/ki.2013.427 · Cited by 336
NAD(P)H Oxidase Mediates TGF-β1–Induced Activation of Kidney Myofibroblasts
Bondi, C. D., Manickam, N., Lee, D. Y., Block, K., Gorin, Y., Abboud, H. E., & Barnes, J. L. (2010) · Journal of the American Society of Nephrology · doi:10.1681/asn.2009020146 · Cited by 297
Metadata
- Authors
- Kitada, M., Koya, D., Sugimoto, T., Isono, M., Araki, S.-I., Kashiwagi, A., & Haneda, M.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2003-10-01
- Volume
- 52
- Issue
- 10
- Pages
- 2603-2614
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2115724806
- Cited by
- 204
- References
- 4
- FWCI
- 9.07
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Kitada, M., Koya, D., Sugimoto, T., Isono, M., Araki, S.-I., Kashiwagi, A., & Haneda, M. (2003). Translocation of Glomerular p47phox and p67phox by Protein Kinase C-β Activation Is Required for Oxidative Stress in Diabetic Nephropathy. Diabetes. https://doi.org/10.2337/diabetes.52.10.2603
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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