Document Detail

Angiotensin II regulation of plasminogen activator inhibitor-1 gene expression in neurons of normotensive and spontaneously hypertensive rat brains.
MedLine Citation:
PMID:  8641204     Owner:  NLM     Status:  MEDLINE    
Neuronal cells in primary culture from the hypothalamus-brain stem areas of normotensive [Wistar-Kyoto (WKY)] and spontaneously hypertensive (SH) rat brains have been used in the present study to investigate an interaction between the brain renin-angiotensin II system and the plasminogen activator system. This is an attempt to further our understanding of the role of brain Ang II in the control of neuronal development and differentiation through its regulation of the extracellular matrix. Ang II caused a 10-fold stimulation of plasminogen activator inhibitor-1 (PAI-1) messenger RNA (mRNA) in WKY rat brain neuronal cultures. The stimulation was mediated by the AT1 receptor subtype and was accompanied by an increase in PAI-1 gene transcription and the synthesis of cellular PAI-1 protein. The stimulation involved activation of protein kinase C, and alterations in the intracellular Ca2+ pool caused a significant inhibition of Ang II stimulation of PAI mRNA. Ang II stimulation of PAI-1 mRNA succeeded its action on c-fos mRNA and was attenuated by c-fos antisense oligonucleotide. Although PAI-1 gene expression was also stimulated by Ang II in neuronal cultures of SH rat brain, two differences between WKY and SH rat brain neurons were observed: 1) the level of Ang II stimulation in SH rat neurons was 50% of that in WKY rat neurons; and 2) Ang II stimulation of c-fos was 2.4-fold higher in SH neurons than in WKY neurons, but c-fos antisense oligonucleotide did not attenuate the stimulatory action of Ang II on PAI-1 mRNA in SH neurons. These observations suggest that the changes in the Ang II-mediated signaling pathways and/or the regulatory region(s) of the PAI-1 gene may contribute to the differential actions of Ang II in WKY and SH rat brain neurons.
K Yu; D Lu; M R Paddy; S E Lenk; M K Raizada
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Endocrinology     Volume:  137     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  1996 Jun 
Date Detail:
Created Date:  1996-07-18     Completed Date:  1996-07-18     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2503-13     Citation Subset:  AIM; IM    
Department of Physiology, University of Florida College of Medicine, Gainesville 32610, USA.
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MeSH Terms
Angiotensin II / pharmacology*
Base Sequence
Brain / metabolism*
Cells, Cultured
Gene Expression Regulation / drug effects*
Genes, fos / drug effects
Hypertension / metabolism*
Molecular Sequence Data
Neurons / metabolism*
Oligonucleotides, Antisense / pharmacology
Plasminogen Activator Inhibitor 1 / genetics*
RNA, Messenger / analysis,  metabolism
Rats, Inbred SHR
Rats, Inbred WKY
Signal Transduction
Grant Support
Reg. No./Substance:
0/Oligonucleotides, Antisense; 0/Plasminogen Activator Inhibitor 1; 0/RNA, Messenger; 11128-99-7/Angiotensin II

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