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A short review on structure and role of cyclic-3',5'-adenosine monophosphate-specific phosphodiesterase 4 as a treatment tool.

Eskandari N, Mirmosayyeb O, Bordbari G, Bastan R, Yousefi Z, Andalib A - J Res Pharm Pract (2015 Oct-Dec)

Bottom Line: Cyclic nucleotide phosphodiesterases (PDEs) are known as a super-family of enzymes which catalyze the metabolism of the intracellular cyclic nucleotides, cyclic-3',5'-adenosine monophosphate (cAMP), and cyclic-3',5'-guanosine monophosphate that are expressed in a variety of cell types that can exert various functions based on their cells distribution.This is because the major isoform of PDE that regulates inflammatory cell activity is the cAMP-specific PDE, PDE4.This review discusses the relationship between PDE4 and its inhibitor drugs based on structures, cells distribution, and pharmacological properties of PDE4 which can be informative for all pharmacy specialists.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Isfahan University of Medical Sciences, Isfahan, Iran ; Applied Physiology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

ABSTRACT
Cyclic nucleotide phosphodiesterases (PDEs) are known as a super-family of enzymes which catalyze the metabolism of the intracellular cyclic nucleotides, cyclic-3',5'-adenosine monophosphate (cAMP), and cyclic-3',5'-guanosine monophosphate that are expressed in a variety of cell types that can exert various functions based on their cells distribution. The PDE4 family has been the focus of vast research efforts over recent years because this family is considered as a prime target for therapeutic intervention in a number of inflammatory diseases such as asthma, chronic obstructive pulmonary disease, and rheumatoid arthritis, and it should be used and researched by pharmacists. This is because the major isoform of PDE that regulates inflammatory cell activity is the cAMP-specific PDE, PDE4. This review discusses the relationship between PDE4 and its inhibitor drugs based on structures, cells distribution, and pharmacological properties of PDE4 which can be informative for all pharmacy specialists.

No MeSH data available.


Related in: MedlinePlus

Diagram showing long (a), short (b) and super-short variants (c) of phosphodiesterase 4 generated by alternative splicing. UCR: Upstream conserved region; LR = Linker region
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Figure 1: Diagram showing long (a), short (b) and super-short variants (c) of phosphodiesterase 4 generated by alternative splicing. UCR: Upstream conserved region; LR = Linker region

Mentions: Further variants of PDE4 are generated by alternative splicing in at least three of the four genes [Figure 1]. From the characterization of PDE4 mRNAs and their corresponding protein products, it has been established that ~20 different PDE4 isoenzymes or variants and at least 35 different PDE4 proteins are expressed in mammalian cells.[24252627] Splice variant isoforms of PDE4 are distinguished by the structure in the N-terminal domain. The alternative mRNA splice variants of PDE4A, PDE4B, PDE4D generally occur at one of two consensus regions within the 5’-end of the transcripts, although an insert occurring in the catalytic domain of PDE4A has also been reported.[28] Depending on the presence of UCR1 and UCR2, PDE4 splice variants can be divided into three major subgroups: (a) “Long forms,” those that contain UCR1 and UCR2 (b) the “short forms,” those which lack UCR1 and have an intact UCR2, and (c) the “super-short form,” with an N-terminally truncated UCR2 [Figure 1]. UCR1 is encoded by three exons,[234] and the long form splice junction is located immediately 5’ to exon 2. Analyses of the human PDE4 genes show that six exons encode the catalytic unit of PDE4 isoenzyme. PDE4, like other PDEs, may exist as a dimer. Since the UCR module mediates dimerization, only long form PDE4 splice variants containing UCR1 and UCR2 are dimerized[29] [Figure 1].


A short review on structure and role of cyclic-3',5'-adenosine monophosphate-specific phosphodiesterase 4 as a treatment tool.

Eskandari N, Mirmosayyeb O, Bordbari G, Bastan R, Yousefi Z, Andalib A - J Res Pharm Pract (2015 Oct-Dec)

Diagram showing long (a), short (b) and super-short variants (c) of phosphodiesterase 4 generated by alternative splicing. UCR: Upstream conserved region; LR = Linker region
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4645128&req=5

Figure 1: Diagram showing long (a), short (b) and super-short variants (c) of phosphodiesterase 4 generated by alternative splicing. UCR: Upstream conserved region; LR = Linker region
Mentions: Further variants of PDE4 are generated by alternative splicing in at least three of the four genes [Figure 1]. From the characterization of PDE4 mRNAs and their corresponding protein products, it has been established that ~20 different PDE4 isoenzymes or variants and at least 35 different PDE4 proteins are expressed in mammalian cells.[24252627] Splice variant isoforms of PDE4 are distinguished by the structure in the N-terminal domain. The alternative mRNA splice variants of PDE4A, PDE4B, PDE4D generally occur at one of two consensus regions within the 5’-end of the transcripts, although an insert occurring in the catalytic domain of PDE4A has also been reported.[28] Depending on the presence of UCR1 and UCR2, PDE4 splice variants can be divided into three major subgroups: (a) “Long forms,” those that contain UCR1 and UCR2 (b) the “short forms,” those which lack UCR1 and have an intact UCR2, and (c) the “super-short form,” with an N-terminally truncated UCR2 [Figure 1]. UCR1 is encoded by three exons,[234] and the long form splice junction is located immediately 5’ to exon 2. Analyses of the human PDE4 genes show that six exons encode the catalytic unit of PDE4 isoenzyme. PDE4, like other PDEs, may exist as a dimer. Since the UCR module mediates dimerization, only long form PDE4 splice variants containing UCR1 and UCR2 are dimerized[29] [Figure 1].

Bottom Line: Cyclic nucleotide phosphodiesterases (PDEs) are known as a super-family of enzymes which catalyze the metabolism of the intracellular cyclic nucleotides, cyclic-3',5'-adenosine monophosphate (cAMP), and cyclic-3',5'-guanosine monophosphate that are expressed in a variety of cell types that can exert various functions based on their cells distribution.This is because the major isoform of PDE that regulates inflammatory cell activity is the cAMP-specific PDE, PDE4.This review discusses the relationship between PDE4 and its inhibitor drugs based on structures, cells distribution, and pharmacological properties of PDE4 which can be informative for all pharmacy specialists.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Isfahan University of Medical Sciences, Isfahan, Iran ; Applied Physiology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

ABSTRACT
Cyclic nucleotide phosphodiesterases (PDEs) are known as a super-family of enzymes which catalyze the metabolism of the intracellular cyclic nucleotides, cyclic-3',5'-adenosine monophosphate (cAMP), and cyclic-3',5'-guanosine monophosphate that are expressed in a variety of cell types that can exert various functions based on their cells distribution. The PDE4 family has been the focus of vast research efforts over recent years because this family is considered as a prime target for therapeutic intervention in a number of inflammatory diseases such as asthma, chronic obstructive pulmonary disease, and rheumatoid arthritis, and it should be used and researched by pharmacists. This is because the major isoform of PDE that regulates inflammatory cell activity is the cAMP-specific PDE, PDE4. This review discusses the relationship between PDE4 and its inhibitor drugs based on structures, cells distribution, and pharmacological properties of PDE4 which can be informative for all pharmacy specialists.

No MeSH data available.


Related in: MedlinePlus