The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Nox4 mediates angiotensin II-induced activation of Akt/protein kinase B in mesangial cells
Abstract
ANG II induces protein synthesis through the serine-threonine kinase Akt/protein kinase B (PKB) in mesangial cells (MCs). The mechanism(s) of activation of Akt/PKB particularly by G protein-coupled receptors, however, is not well characterized. We explored the role of the small GTPase Rac1, a component of the phagocyte NADPH oxidase, and the gp91 phox homologue Nox4/Renox in this signaling pathway. ANG II causes rapid activation of Rac1, an effect abrogated by phospholipase A 2 inhibition and mimicked by arachidonic acid (AA). Northern blot analysis revealed high levels of Nox4 transcript in MCs and transfection with antisense (AS) oligonucleotides for Nox4 markedly decreased NADPH-dependent reactive oxygen species (ROS)-producing activity. Dominant negative Rac1 (N17Rac1) as well as AS Nox4 inhibited ROS generation in response to ANG II and AA, whereas constitutively active Rac1 stimulated ROS formation. Moreover, N17Rac1 blocked stimulation of NADPH oxidase activity by AA. N17Rac1 or AS Nox4 abolished ANG II- or AA-induced activation of the hypertrophic kinase Akt/PKB. In addition, AS Nox4 inhibited ANG II-induced protein synthesis. These data provide the first evidence that activation by AA of a Rac1-regulated, Nox4-based NAD(P)H oxidase and subsequent generation of ROS mediate the effect of ANG II on Akt/PKB activation and protein synthesis in MCs.
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Cites
NAD(P)H Oxidase: Role in Cardiovascular Biology and Disease
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Identification of Renox, an NAD(P)H oxidase in kidney
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Toll-like receptor 2–mediated NF-κB activation requires a Rac1-dependent pathway
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A Novel Superoxide-producing NAD(P)H Oxidase in Kidney
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Regulation of reactive-oxygen-species generation in fibroblasts by Rac 1
SUNDARESAN, M., YU, Z.-X., FERRANS, V. J., SULCINER, D. J., GUTKIND, S., IRANI, K. J., GOLDSCHMIDT-CLERMONT, P. J., & FINKEL, T. (1996) · Biochemical Journal · doi:10.1042/bj3180379 · Cited by 486
Cited by
The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology
Bedard, K., & Krause, K.-H. (2007) · Physiological Reviews · doi:10.1152/physrev.00044.2005 · Cited by 6,989
NADPH oxidases: An overview from structure to innate immunity-associated pathologies
Panday, A., Sahoo, M. K., Osorio, D., & Batra, S. (2015) · Cellular & Molecular Immunology · doi:10.1038/cmi.2014.89 · Cited by 944
Nox proteins in signal transduction
Brown, D. I., & Griendling, K. K. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.07.023 · Cited by 832
Sautin, Y. Y., Nakagawa, T., Zharikov, S., & Johnson, R. J. (2007) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00600.2006 · Cited by 787
Functional analysis of Nox4 reveals unique characteristics compared to other NADPH oxidases
Martyn, K. D., Frederick, L. M., von Loehneysen, K., Dinauer, M. C., & Knaus, U. G. (2006) · Cellular Signalling · doi:10.1016/j.cellsig.2005.03.023 · Cited by 783
Metadata
- Authors
- Gorin, Y., Ricono, J. M., Kim, N.-H., Bhandari, B., Choudhury, G. G., & Abboud, H. E.
- Venue
- American Journal of Physiology-Renal Physiology
- Publisher
- American Physiological Society
- Published
- 2003-08
- Volume
- 285
- Issue
- 2
- Pages
- F219-F229
- ISSN
- 1522-1466 (ISSN-L)
- 1931-857X
- OpenAlex
- W2019063477
- Cited by
- 277
- References
- 45
- FWCI
- 9.64
- Type
- journal article
- Language
- en
- Open access
- closed
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- Gorin, Y., Ricono, J. M., Kim, N.-H., Bhandari, B., Choudhury, G. G., & Abboud, H. E. (2003). Nox4 mediates angiotensin II-induced activation of Akt/protein kinase B in mesangial cells. American Journal of Physiology-Renal Physiology. https://doi.org/10.1152/ajprenal.00414.2002
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