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Role of PDE3A in regulation of cell cycle progression in mouse vascular smooth muscle cells and oocytes: implications in cardiovascular diseases and infertility.
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- Author(s): Begum N;Begum N; Shen W; Manganiello V
- Source:
Current opinion in pharmacology [Curr Opin Pharmacol] 2011 Dec; Vol. 11 (6), pp. 725-9. Date of Electronic Publication: 2011 Nov 01.
- Publication Type:
Journal Article; Research Support, N.I.H., Intramural; Review
- Language:
English
- Additional Information
- Source:
Publisher: Elsevier Science Ltd Country of Publication: England NLM ID: 100966133 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1471-4973 (Electronic) Linking ISSN: 14714892 NLM ISO Abbreviation: Curr Opin Pharmacol Subsets: MEDLINE
- Publication Information:
Original Publication: Oxford : Elsevier Science Ltd., 2001-
- Subject Terms:
Cell Cycle*/
drug effects;
Cardiovascular Diseases/
*drug therapy ;
Cyclic Nucleotide Phosphodiesterases, Type 3/
*metabolism ;
Infertility, Female/
*drug therapy ;
Muscle, Smooth, Vascular/
*enzymology ;
Oocytes/
*enzymology ;
Phosphodiesterase 3 Inhibitors/
*pharmacology;
Animals ;
Cardiovascular Diseases/
enzymology ;
Cardiovascular Diseases/
metabolism ;
Cell Proliferation/
drug effects ;
Cyclic AMP/
antagonists & inhibitors ;
Cyclic AMP/
physiology ;
Cyclic Nucleotide Phosphodiesterases, Type 3/
chemistry ;
Cyclic Nucleotide Phosphodiesterases, Type 3/
genetics ;
Female ;
Humans ;
Infertility, Female/
enzymology ;
Infertility, Female/
metabolism ;
Isoenzymes/
antagonists & inhibitors ;
Isoenzymes/
genetics ;
Isoenzymes/
metabolism ;
Male ;
Mesothelin ;
Mice ;
Mice, Knockout ;
Molecular Targeted Therapy ;
Muscle, Smooth, Vascular/
drug effects ;
Muscle, Smooth, Vascular/
metabolism ;
Oocytes/
drug effects ;
Oocytes/
metabolism ;
Oogenesis/
drug effects ;
Phosphodiesterase 3 Inhibitors/
therapeutic use ;
Signal Transduction/
drug effects - Abstract:
Phosphodiesterase-3 (PDE3) is a major cAMP-hydrolyzing PDE in vascular smooth muscle cells (VSMCs) and oocytes. The exact role and contribution of the two PDE3 isoforms, PDE3A and PDE3B, in VSMC growth regulation and oocyte maturation was examined using PDE3A (3A) and PDE3B (3B) knockout (KO) mouse models. PDE3A-deficient VSMCs exhibit marked reduction in mitogen-induced cell growth due to cell cycle arrest at G₀-G₁ phase, which resulted from dysregulation of cAMP/protein kinase A (PKA)-activated and mitogen-activated protein kinase (MAPK)-signaling pathways, as well as from alterations in key cell cycle regulatory proteins. Similarly, PDE3A-deficient oocytes exhibit cell cycle arrest at G₂/M phase because increased cAMP/PKA signaling in KO oocytes most likely inhibits Cdc25B-catalyzed dephosphorylation/activation of Cdc2 (maturation promoting factor (MPF)), a key regulator of G₂/M transition.
(Copyright © 2011 Elsevier Ltd. All rights reserved.)
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- Grant Information:
ZIA HL002540-17 United States Intramural NIH HHS
- Accession Number:
0 (Isoenzymes)
0 (Msln protein, mouse)
0 (Phosphodiesterase 3 Inhibitors)
E0399OZS9N (Cyclic AMP)
EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 3)
EC 3.1.4.17 (PDE3A protein, human)
EC 3.1.4.17 (Pde3a protein, mouse)
J27WDC343N (Mesothelin)
- Publication Date:
Date Created: 20111105 Date Completed: 20120423 Latest Revision: 20211203
- Publication Date:
20221213
- Accession Number:
PMC3225595
- Accession Number:
10.1016/j.coph.2011.10.006
- Accession Number:
22051884
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