Conserved expression and functions of PDE4 in rodent and human heart

Autor: Moses Xie, Colleen Scheitrum, Judith Krall, Matthew A. Movsesian, Marco Conti, Wito Richter
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Rodent
Physiology
Cardiorespiratory Medicine and Haematology
Mice
Cyclic AMP
Medicine & Public Health
Myocyte
Myocytes
Cardiac
Phosphorylation
Cells
Cultured
Cultured
biology
Original Contribution
Isoenzymes
RNA splicing
Type 4
Cardiology and Cardiovascular Medicine
Cardiac
Cyclic Nucleotide Phosphodiesterases
medicine.medical_specialty
Cells
Cardiology
Heart failure
Isozyme
Enzyme activator
Downregulation and upregulation
Internal medicine
biology.animal
Physiology (medical)
cAMP
medicine
Animals
Humans
Heart Failure
Myocytes
Myocardium
3′
5′-Cyclic nucleotide phosphodiesterase
medicine.disease
Cyclic AMP-Dependent Protein Kinases
Cyclic Nucleotide Phosphodiesterases
Type 4
Rats
5 '-Cyclic nucleotide phosphodiesterase
Enzyme Activation
'
Endocrinology
Cardiovascular System & Hematology
Human heart
PDE4
Zdroj: Richter, Wito; Xie, Moses; Scheitrum, Colleen; Krall, Judith; Movsesian, Matthew A.; & Conti, Marco. (2011). Conserved expression and functions of PDE4 in rodent and human heart. Basic Research in Cardiology, 106(2), pp 249-262. doi: 10.1007/s00395-010-0138-8. Retrieved from: http://www.escholarship.org/uc/item/75c430rd
Basic research in cardiology, vol 106, iss 2
Basic Research in Cardiology
DOI: 10.1007/s00395-010-0138-8.
Popis: PDE4 isoenzymes are critical in the control of cAMP signaling in rodent cardiac myocytes. Ablation of PDE4 affects multiple key players in excitation–contraction coupling and predisposes mice to the development of heart failure. As little is known about PDE4 in human heart, we explored to what extent cardiac expression and functions of PDE4 are conserved between rodents and humans. We find considerable similarities including comparable amounts of PDE4 activity expressed, expression of the same PDE4 subtypes and splicing variants, anchoring of PDE4 to the same subcellular compartments and macromolecular signaling complexes, and downregulation of PDE4 activity and protein in heart failure. The major difference between the species is a fivefold higher amount of non-PDE4 activity in human hearts compared to rodents. As a consequence, the effect of PDE4 inactivation is different in rodents and humans. PDE4 inhibition leads to increased phosphorylation of virtually all PKA substrates in mouse cardiomyocytes, but increased phosphorylation of only a restricted number of proteins in human cardiomyocytes. Our findings suggest that PDE4s have a similar role in the local regulation of cAMP signaling in rodent and human heart. However, inhibition of PDE4 has ‘global’ effects on cAMP signaling only in rodent hearts, as PDE4 comprises a large fraction of the total cardiac PDE activity in rodents but not in humans. These differences may explain the distinct pharmacological effects of PDE4 inhibition in rodent and human hearts. Electronic supplementary material The online version of this article (doi:10.1007/s00395-010-0138-8) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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