Back to Search
Start Over
Involvement of peptidyl-prolyl isomerase Pin1 in the inhibitory effect of fluvastatin on endothelin-1-induced cardiomyocyte hypertrophy.
- Source :
-
Life sciences [Life Sci] 2014 May 02; Vol. 102 (2), pp. 98-104. Date of Electronic Publication: 2014 Mar 21. - Publication Year :
- 2014
-
Abstract
- Aims: Cardiac hypertrophy is elicited by endothelin (ET)-1 as well as other neurohumoral factors, hemodynamic overload, and oxidative stress; HMG-CoA reductase inhibitors (statins) were shown to inhibit cardiac hypertrophy partly via the anti-oxidative stress. One of their common intracellular pathways is the phosphorylation cascade of MEK signaling. Pin1 specifically isomerizes the phosphorylated protein with Ser/Thr-Pro bonds and regulates their activity through conformational changes. There is no report whether the Pin1 activation contributes to ET-1-induced cardiomyocyte hypertrophy and whether the Pin1 inactivation contributes to the inhibitory effect of statins. The aim of this study was to reveal these questions.<br />Main Methods: We assessed neonatal rat cardiomyocyte hypertrophy using ET-1 and fluvastatin by the cell surface area, ANP mRNA expression, JNK and c-Jun phosphorylation, and [(3)H]-leucine incorporation.<br />Key Findings: Fluvastatin inhibited ET-1-induced increase in the cell surface area, ANP expression, and [(3)H]-leucine incorporation; and it suppressed the signaling cascade from JNK to c-Jun. The phosphorylated Pin1 level, an inactive form, was decreased by ET-1; however, it reached basal level by fluvastatin. Furthermore, Pin1 overexpression clearly elicited cardiomyocyte hypertrophy, which was inhibited by fluvastatin.<br />Significance: This is the first report that ET-1-induced cardiomyocyte hypertrophy is mediated through the Pin1 activation and that the inhibitory effect of fluvastatin on cardiomyocyte hypertrophy would partly be attributed to the suppression of the Pin1 function. This study firstly suggests that Pin1 determines the size of hypertrophied cardiomyocyte by regulating the activity of phosphorylated molecules and that statins exert their pleiotropic effects partly via Pin1 inactivation.<br /> (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Animals, Newborn
Cardiomegaly chemically induced
Cardiomegaly metabolism
Cells, Cultured
Endothelin-1 antagonists & inhibitors
Fatty Acids, Monounsaturated therapeutic use
Fluvastatin
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use
Indoles therapeutic use
Myocytes, Cardiac drug effects
Myocytes, Cardiac pathology
NIMA-Interacting Peptidylprolyl Isomerase
Peptidylprolyl Isomerase antagonists & inhibitors
Peptidylprolyl Isomerase biosynthesis
Rats
Rats, Sprague-Dawley
Treatment Outcome
Cardiomegaly prevention & control
Endothelin-1 toxicity
Fatty Acids, Monounsaturated pharmacology
Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology
Indoles pharmacology
Myocytes, Cardiac metabolism
Peptidylprolyl Isomerase physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0631
- Volume :
- 102
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Life sciences
- Publication Type :
- Academic Journal
- Accession number :
- 24657892
- Full Text :
- https://doi.org/10.1016/j.lfs.2014.03.018