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In vivo, the atropine-dependent prolongation of heart rate increase was blunted in PDE4D but not in wildtype or PDE4B knockout mice. The authors propose that inhibition of PDE4 by atropine accounts, at least in part, for the induction of tachycardia and the arrhythmogenic potency of this drug.
Study combined mutational analysis in the Apc mutated mice with published studies of frank colon cancer in patients to deduce that Pde4b has two strong biological functions. It negatively regulates colonic adenomagenesis in Apc mutated mice. In patients, PDE4B is most commonly inactivated by an epigenetic process.
PDE4B-deficient mice displayed an increased circulating IL-1Ra, suggesting a protective role of PDE4B inactivation in vivo.
PDE4B1-D564A transgenic mice demonstrate increased phosphorylation of CREB and ERK1/2, consistent with activation of PKA, ERK1/2 and potentially other kinases, increased hippocampal neurogenesis, and alterations in hippocampal slice electrophysiology consistent with augmentation of hippocampal long-term potentiation. Mice are more active but have no major changes in associative learning or other behavior.
Pharmacologic and gene knock-out results suggest that Pde4b plays a critical role in coordinating alcohol-induced, peripheral endotoxemia mediated neuro-inflammation and could serve as a significant therapeutic target.
These results indicate that Phosphodiesterase-4B overexpression may be involved in the development of surgery-induced cognitive dysfunction in mice.
These results demonstrate that the alcohol- induced increase in hepatic Pde4, specifically Pde4b expression, and compromised cAMP signalling predispose the liver to impaired fatty acid oxidation and the development of steatosis.
Data establish specific inhibition of phosphodiesterase-4B as a promising therapeutic approach for disorders of cognition and anxiety, and a putative target for pathological fear memory.
PDE4B phosphorylated by AMPK at Ser304 is important for activation.
Lymphomas developing in a Pde4b-null background display significantly lower microvessel density in association with lower VEGF levels and PI3K/AKT activity.
The results point to a possible role of PDE4B2 splice variant during Experimental autoimmune encephalomyelitis pathogenesis
Clear differences are observed in PDE4B3 mRNA expression levels in males compared with females in a time-dependent manner.
Genetic variations in DISC1 influence formation of biochemical complex with PDE4 and GSK-3 and strengthen the possibility of synergistic interactions between these proteins.
PDE4B-deficient mice display impaired reversal learning in the Morris water maze compared to wild-type littermates.
Results identify PDE4B in the CaV1.2 complex as a critical regulator of ICa during beta-AR stimulation and suggest that distinct PDE4 subtypes are important for normal regulation of calcium-induced calcium release in cardiomyocytes.
Findings demonstrate that PDE4D and PDE4B have specialized functions in mouse embryonic fibroblasts with PDE4B controlling cAMP in a discrete subdomain near the plasma membrane.
induction is esssential for LPS-activated tnf-alpha responses
PDE4B mediates the antipsychotic effects of rolipram in conditioned avoidance responding; the PDE4B-regulated cyclic adenosine monophosphate signaling pathway may play a role in the pathophysiology and pharmacotherapy of psychosis
the PDE4B subfamily is involved in signaling pathways that contribute to anxiogenic-like effects on behavior.
Altered DISC1-PDE4B interaction may thus underlie the symptoms of some cases of schizophrenia and depression.(Review)
PDE4B gene may play a role in the pathogenesis of OLP.
Data suggest that maternal glycemic response during pregnancy is associated with lower DNA methylation of 4 CpG sites within PDE4B gene in placenta (collected after term birth); 3 additional CpG sites are differentially methylated relative to maternal glucose response within TNFRSF1B, LDLR, and BLM genes. (TNFRSF1B = TNF receptor superfamily member-1B; LDLR = low density lipoprotein receptor; BLM = Bloom syndrome protein)
Smurf2, an E3 ubiquitin ligase, interacts with PDE4B and attenuates liver fibrosis through miR-132 mediated CTGF inhibition.
HTT forms a ternary protein complex with the scaffolding protein DISC1 and cAMP-degrading phosphodiesterase 4 (PDE4) to regulate PDE4 activity.
Low PDE4B expression is associated with sepsis.
PDE4B gene may be involved in the testicular abnormalities of men with DS and cryptorchidism.
This meta-analysis suggests that PDE4B SNPs are genetically associated with susceptibility to schizophrenia.
Our results suggest that PDE4B does not play an important role during the chemotactic response of human neutrophils
Our results support previously reported association of PDE4B variations with schizophrenia in other populations.
analysis of the mechanism underlying synergistic up-regulation of PDE4B2 via a cross-talk between PKA-Cbeta and p65
ototopical post-inoculation administration of a PDE4 inhibitor suppresses inflammation in this animal model, thus demonstrating the therapeutic potential of targeting PDE4
PDE4B was found to be highly expressed in CD4+ lymphoid cancer cells, which suggests that it may represent a physiological role unique to the CD8+ and lymphoid cancer cells and thus might represent a target for treatment of certain lymphoid diseases
Short Disrupted-in-Schizophrenia (DISC)1 splice variants show reduced or no binding to nudE nuclear distribution E homolog (NDEL)1 and PDE4B proteins but fully interact with fasciculation/elongation zeta (FEZ)1 and glycogen synthase kinase 3 GSK3beta.
PDE4B mediates ERK-dependent up-regulation of mucin MUC5AC by S. pneumoniae by inhibiting cAMP-PKA-dependent MKP-1 pathway.
a study of Northwestern Han Chinese found that rs472952 is significantly associated with schizophrenia (SCZ) and rs7537440 is associated with SCZ in females; results provide further evidence that PDE4B may play important roles in the etiology of SCZ
PDE4B was downregulated and the protein kinase A pathway was activated in castration-resistant LNCaP prostate cancer cells. PDE4B expression was reduced in advanced prostate cancer and PDE4B knockdown promoted castration-resistant growth of LNCaP cells.
The reported anti-inflammatory activity of bresol might be attributed to its abilities to inhibit PDE4B and thus elevate cAMP levels in human monocytes.
Overexpression of the PDE4B in diffuse large B-cell lymphoma (DLBCL) impinge on the same genes/pathways that are abnormally active in GC-resistant tumors.
found a significant association between PDE4B and PD in the haplotype analysis. Sex-specific analyses demonstrated that PDE4B was associated with PD in females. results suggest PDE4B may play a role in the pathophysiology of PD in the Japanese population.
QTL-CI for IMF was reconfirmed with high significance, and its position was narrowed down to an interval of 4 cM (the region defined by markers PDE4B and SW1881)
This gene is a member of the type IV, cyclic AMP (cAMP)-specific, cyclic nucleotide phosphodiesterase (PDE) family. Cyclic nucleotides are important second messengers that regulate and mediate a number of cellular responses to extracellular signals, such as hormones, light, and neurotransmitters. The cyclic nucleotide phosphodiesterases (PDEs) regulate the cellular concentrations of cyclic nucleotides and thereby play a role in signal transduction. This gene encodes a protein that specifically hydrolyzes cAMP. Altered activity of this protein has been associated with schizophrenia and bipolar affective disorder. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.
phosphodiesterase 4B, cAMP-specific (phosphodiesterase E4 dunce homolog)
, phosphodiesterase 4B, cAMP-specific
, phosphodiesterase 4B
, 3',5'-cyclic AMP phosphodiesterase
, Phosphodiesterase 4B cAMP-specific (dunce
, Phosphodiesterase 4B, cAMP-specific (dunce
, cAMP-specific 3',5'-cyclic phosphodiesterase 4B
, cAMP-specific phosphodiesterase-4 B isoform
, dunce-like phosphodiesterase E4
, phosphodiesterase 4B, cAMP-specific (phosphodiesterase E4 dunce homolog, Drosophila)
, phosphodiesterase 4B, cAMP specific