PMID- 19409874 OWN - NLM STAT- MEDLINE DCOM- 20090609 LR - 20211020 IS - 1090-2104 (Electronic) IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 384 IP - 2 DP - 2009 Jun 26 TI - The angiotensin II-AT1 receptor stimulates reactive oxygen species within the cell nucleus. PG - 149-54 LID - 10.1016/j.bbrc.2009.04.126 [doi] AB - We and others have reported significant expression of the Ang II Type 1 receptor (AT1R) on renal nuclei; thus, the present study assessed the functional pathways and distribution of the intracellular AT1R on isolated nuclei. Ang II (1nM) stimulated DCF fluorescence, an intranuclear indicator of reactive oxygen species (ROS), while the AT1R antagonist losartan or the NADPH oxidase (NOX) inhibitor DPI abolished the increase in ROS. Dual labeling of nuclei with antibodies against nucleoporin 62 (Nup62) and AT1R or the NADPH oxidase isoform NOX4 revealed complete overlap of the Nup62 and AT1R (99%) by flow cytometry, while NOX4 was present on 65% of nuclei. Treatment of nuclei with a PKC agonist increased ROS while the PKC inhibitor GF109203X or PI3 kinase inhibitor LY294002 abolished Ang II stimulation of ROS. We conclude that the Ang II-AT1R-PKC axis may directly influence nuclear function within the kidney through a redox sensitive pathway. FAU - Pendergrass, Karl D AU - Pendergrass KD AD - The Hypertension and Vascular Research Center, Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. FAU - Gwathmey, Tanya M AU - Gwathmey TM FAU - Michalek, Ryan D AU - Michalek RD FAU - Grayson, Jason M AU - Grayson JM FAU - Chappell, Mark C AU - Chappell MC LA - eng GR - P01 HL051952/HL/NHLBI NIH HHS/United States GR - HD-47584/HD/NICHD NIH HHS/United States GR - R01 HL056973/HL/NHLBI NIH HHS/United States GR - R01 HL056973-09/HL/NHLBI NIH HHS/United States GR - HL-56973/HL/NHLBI NIH HHS/United States GR - P01 HL051952-150007/HL/NHLBI NIH HHS/United States GR - HD-17644/HD/NICHD NIH HHS/United States GR - R29 HL056973/HL/NHLBI NIH HHS/United States GR - HL-51952/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20090503 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Angiotensin II Type 1 Receptor Blockers) RN - 0 (Indoles) RN - 0 (Maleimides) RN - 0 (Reactive Oxygen Species) RN - 0 (Receptor, Angiotensin, Type 1) RN - EC 2.7.11.13 (Protein Kinase C) RN - JMS50MPO89 (Losartan) RN - L79H6N0V6C (bisindolylmaleimide I) SB - IM MH - Angiotensin II Type 1 Receptor Blockers/pharmacology MH - Animals MH - Cell Nucleus/*metabolism MH - Indoles/pharmacology MH - Kidney/cytology/*metabolism MH - Losartan/pharmacology MH - Male MH - Maleimides/pharmacology MH - Protein Kinase C/antagonists & inhibitors/metabolism MH - Rats MH - Rats, Inbred Lew MH - Reactive Oxygen Species/*metabolism MH - Receptor, Angiotensin, Type 1/*metabolism PMC - PMC2688692 MID - NIHMS114065 EDAT- 2009/05/05 09:00 MHDA- 2009/06/10 09:00 PMCR- 2010/06/26 CRDT- 2009/05/05 09:00 PHST- 2009/03/13 00:00 [received] PHST- 2009/04/15 00:00 [accepted] PHST- 2009/05/05 09:00 [entrez] PHST- 2009/05/05 09:00 [pubmed] PHST- 2009/06/10 09:00 [medline] PHST- 2010/06/26 00:00 [pmc-release] AID - S0006-291X(09)00778-5 [pii] AID - 10.1016/j.bbrc.2009.04.126 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2009 Jun 26;384(2):149-54. doi: 10.1016/j.bbrc.2009.04.126. Epub 2009 May 3.