|High-glucose-induced regulation of intracellular ANG II synthesis and nuclear redistribution in cardiac myocytes.|
|PMID: 17483239 Owner: NLM Status: MEDLINE|
|The prevailing paradigm is that cardiac ANG II is synthesized in the extracellular space from components of the circulating and/or local renin-angiotensin system. The recent discovery of intracrine effects of ANG II led us to determine whether ANG II is synthesized intracellularly in neonatal rat ventricular myocytes (NRVM). NRVM, incubated in serum-free medium, were exposed to isoproterenol or high glucose in the absence or presence of candesartan, which was used to prevent angiotensin type 1 (AT(1)) receptor-mediated internalization of ANG II. ANG II was measured in cell lysates and the culture medium, which represented intra- and extracellularly synthesized ANG II, respectively. Isoproterenol increased ANG II concentration in cell lysates and medium of NRVM in the absence or presence of candesartan. High glucose markedly increased ANG II synthesis only in cell lysates in the absence and presence of candesartan. Western analysis showed increased intracellular levels of angiotensinogen, renin, and chymase in high-glucose-exposed cells. Confocal immunofluorocytometry confirmed the presence of ANG II in the cytoplasm and nucleus of high-glucose-exposed NRVM and along the actin filaments in isoproterenol-exposed cells. ANG II synthesis was dependent on renin and chymase in high-glucose-exposed cells and on renin and angiotensin-converting enzyme in isoproterenol-exposed cells. In summary, the site of ANG II synthesis, intracellular localization, and the synthetic pathway in NRVM are stimulus dependent. Significantly, NRVM synthesized and retained ANG II intracellularly, which redistributed to the nucleus under high-glucose conditions, suggesting a role for an intracrine mechanism in diabetic conditions.|
|Vivek P Singh; Bao Le; Vadiraja B Bhat; Kenneth M Baker; Rajesh Kumar|
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|Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-05-04|
|Title: American journal of physiology. Heart and circulatory physiology Volume: 293 ISSN: 0363-6135 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2007 Aug|
|Created Date: 2007-08-03 Completed Date: 2007-09-18 Revised Date: 2013-05-28|
Medline Journal Info:
|Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States|
|Languages: eng Pagination: H939-48 Citation Subset: IM|
|Division of Molecular Cardiology, Cardiovascular Research Institute, Texas A & M Health Science Center, College of Medicine, Temple, TX 76504, USA.|
|APA/MLA Format Download EndNote Download BibTex|
Active Transport, Cell Nucleus
Angiotensin II / biosynthesis*
Angiotensin II Type 1 Receptor Blockers / pharmacology
Angiotensinogen / biosynthesis
Benzimidazoles / pharmacology
Cell Nucleus / drug effects, metabolism*
Chymases / biosynthesis
Cytoplasm / metabolism
Dose-Response Relationship, Drug
Extracellular Space / metabolism
Glucose / metabolism*, pharmacology
Heart Ventricles / cytology, metabolism
Isoproterenol / pharmacology
Myocytes, Cardiac / drug effects, enzymology, metabolism*
Peptidyl-Dipeptidase A / metabolism
Receptor, Angiotensin, Type 1 / metabolism
Renin / biosynthesis
Renin-Angiotensin System* / drug effects
Sympathomimetics / pharmacology
Tetrazoles / pharmacology
|0/Angiotensin II Type 1 Receptor Blockers; 0/Benzimidazoles; 0/Receptor, Angiotensin, Type 1; 0/Sympathomimetics; 0/Tetrazoles; 11002-13-4/Angiotensinogen; 11128-99-7/Angiotensin II; 50-99-7/Glucose; 7683-59-2/Isoproterenol; EC 220.127.116.11/Peptidyl-Dipeptidase A; EC 18.104.22.168/Chymases; EC 22.214.171.124/Renin; S8Q36MD2XX/candesartan|
|Am J Physiol Heart Circ Physiol. 2007 Aug;293(2):H905-6
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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