The binding of Captopril to Angiotensin-I Converting Enzyme triggers signaling pathways activation

The binding of Captopril to Angiotensin-I Converting Enzyme triggers signaling pathways activation Hypertension is a global health problem and ACE inhibitors are largely used to control this pathology. Recently, it has been shown that ACE can also act as a transducer signal molecule when its inhibitors or substrates bind to it. This new role of ACE could contribute to understanding some of the effects not explained by its catalytic activity only. In this study we investigated signaling pathways activation in Chinese hamster ovary (CHO) cells stably expressing ACE (CHO-ACE) under different treatments. We also investigated gene modulation after 4h and 24h captopril treatments. Our results demonstrated that CHO-ACE cells when stimulated with AngI, ramipril or captopril led to JNK and ERK1/2 phosphorylation. To verify any physiological role at endogenous level we made use of primary cultures of mesangial cells from spontaneously hypertensive rats (SHR) and Wistar rats. Our results showed that ERK1/2 activation occurred only in primary cultures of mesangial cells from SHR rats upon captopril stimulation suggesting that this signaling pathway is differentially regulated during hypertension. Our results also showed that captopril treatment leads to decrease of COX2, interleukin 1β and β-arrestin 2 gene expression level.Our findings strengthen the fact that in addition to the blockage of enzymatic activity, ACE inhibitors also trigger signaling pathways activation and this may contribute to their beneficial effects in the treatment of hypertension and other pathologies. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Cell Physiology The American Physiological Society

The binding of Captopril to Angiotensin-I Converting Enzyme triggers signaling pathways activation

Loading next page...
 
/lp/aps/the-binding-of-captopril-to-angiotensin-i-converting-enzyme-triggers-TVAczqvD98
ISSN
0363-6143
eISSN
1522-1563
D.O.I.
10.1152/ajpcell.00012.2016
Publisher site
See Article on Publisher Site

Abstract

Hypertension is a global health problem and ACE inhibitors are largely used to control this pathology. Recently, it has been shown that ACE can also act as a transducer signal molecule when its inhibitors or substrates bind to it. This new role of ACE could contribute to understanding some of the effects not explained by its catalytic activity only. In this study we investigated signaling pathways activation in Chinese hamster ovary (CHO) cells stably expressing ACE (CHO-ACE) under different treatments. We also investigated gene modulation after 4h and 24h captopril treatments. Our results demonstrated that CHO-ACE cells when stimulated with AngI, ramipril or captopril led to JNK and ERK1/2 phosphorylation. To verify any physiological role at endogenous level we made use of primary cultures of mesangial cells from spontaneously hypertensive rats (SHR) and Wistar rats. Our results showed that ERK1/2 activation occurred only in primary cultures of mesangial cells from SHR rats upon captopril stimulation suggesting that this signaling pathway is differentially regulated during hypertension. Our results also showed that captopril treatment leads to decrease of COX2, interleukin 1β and β-arrestin 2 gene expression level.Our findings strengthen the fact that in addition to the blockage of enzymatic activity, ACE inhibitors also trigger signaling pathways activation and this may contribute to their beneficial effects in the treatment of hypertension and other pathologies.

Journal

AJP - Cell PhysiologyThe American Physiological Society

Published: Jan 13, 2016

There are no references for this article.

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off