In cardiac myocytes, cAMP elevation triggers the down-regulation of transcripts and promoter activity for cyclic AMP phosphodiesterase-4A10 (PDE4A10)

McCahill, Angela; Campbell, Lachlan; McSorley, Theresa; Sood, Arvind; Lynch, Martin J.; Li, Xiang; Yan, Chen; Baillie, George S.; Houslay, Miles D.

doi:10.1016/j.cellsig.2008.07.017

Cited by 17 publications

(17 citation statements)

References 89 publications

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“…1E and F). These inferences are also in agreement with reports showing that: (1) intracellular cAMP content can modulate the expression and activities of PDE4 (Lania et al, 1998;McCahill et al, 2008); and (2) PDE4 accounted for >80% of PDE activity in human and rodent skeletal muscle (Bloom, 2002;Hinkle et al, 2005a). It appears therefore that intracellular cAMP and PDE4 operate in a closed feedback loop in maintaining each other's levels and activities, and any stimuli (e.g., cachexia) that disrupt this closed loop can lead to the loss of skeletal muscle integrity.…”

Section: Discussionsupporting

confidence: 91%

“…Likewise, changes in intracellular cAMP levels have also been reported to modulate the expression and activity of PDE4 isoforms (Lania et al, 1998;McCahill et al, 2008). This observation, and our findings that burn decreased muscle cAMP content and that torbafylline normalized it, led us to investigate the PDE4 activity in the gastrocnemius muscle obtained after in vivo treatment of burn rats with torbafylline.…”

Section: Resultssupporting

confidence: 48%

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Phosphodiesterase (PDE) inhibitor torbafylline (HWA 448) attenuates burn-induced rat skeletal muscle proteolysis through the PDE4/cAMP/EPAC/PI3K/Akt pathway

Joshi

Kadeer²,

Sheriff

et al. 2014

Molecular and Cellular Endocrinology

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Section: Discussionsupporting

confidence: 91%

Section: Resultssupporting

confidence: 48%

Phosphodiesterase (PDE) inhibitor torbafylline (HWA 448) attenuates burn-induced rat skeletal muscle proteolysis through the PDE4/cAMP/EPAC/PI3K/Akt pathway

Joshi

Kadeer²,

Sheriff

et al. 2014

Molecular and Cellular Endocrinology

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“…4D) 15), perhaps via a compensatory feedback loop (7,8). However, recent studies have shown that cAMP, via the induction of ICER, can decrease PDE3A and PDE4A10 in cardiac myocytes (44,45). The decrease in PDE7B expression that we observe with increasing cAMP may be due to a similar transcriptional mechanism or to the increase in cell killing, i.e., a depletion of the CLL cells that express a high level of this PDE isoform.…”

Section: Discussionmentioning

confidence: 34%

Cyclic nucleotide phosphodiesterase profiling reveals increased expression of phosphodiesterase 7B in chronic lymphocytic leukemia

Zhang¹,

Murray²,

Zahno³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Cyclic nucleotide phosphodiesterase (PDE) isoforms can influence disease pathogenesis and be novel therapeutic targets. Because lower cAMP levels may contribute to the decreased apoptosis that occurs in chronic lymphocytic leukemia (CLL), we assessed the expression levels of PDE isoforms in peripheral blood mononuclear cells (PBMC) of healthy adults and patients with CLL. We found a unique PDE mRNA signature in CLL: higher levels than in normal PBMC of PDE7B (increased Ϸ23-fold) and lower levels of PDE3B, 4D, 5A, and 9A mRNA (each decreased Ϸ30-fold). Increased PDE7B mRNA in CLL correlates with a 10-fold-higher expression of PDE7B protein and results in an increased contribution of PDE7 to total PDE activity. Consistent with the higher level of PDE7B expression, inhibitors of PDE7 (BRL-50481, IR-202) and a dual PDE4/PDE7 inhibitor (IR-284) selectively increase apoptosis in CLL cells compared with normal PBMC or B cells. Apoptosis of CLL cells promoted by inhibitors of PDE7 and PDE4/7 is attenuated by PKA inhibition, occurs via a mitochondrial-dependent process, and is associated with increased cAMP accumulation and down-regulation of the antiapoptotic protein survivin and of PDE7B. The increase in PDE7B expression and PDE7 inhibitor-promoted apoptosis implicates PDE7B as a drug target in CLL. Our findings identify a unique PDE signature in CLL and illustrate the utility of broad analyses of PDE isoform expression in human disease.apoptosis ͉ B cell ͉ cAMP ͉ survivin

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“…For instance, the PDE4 inhibitor rolipram has been reported to stimulate ICER expression in mouse osteoblastic cells (5). In addition, in cardiac myocytes, cAMP elevation triggers the downregulation of transcripts and promoter activity for cyclic AMP PDE4A10 (23).…”

Section: Discussionmentioning

confidence: 99%

NCS 613, a potent and specific PDE4 inhibitor, displays anti-inflammatory effects on human lung tissues

Yougbaré

Morin²,

Senouvo³

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

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Chronic inflammation is a hallmark of pulmonary diseases, which leads to lung parenchyma destruction (emphysema) and obstructive bronchiolitis occurring in both chronic obstructive pulmonary disease and asthma. Inflammation is strongly correlated with low intracellular cAMP levels and increase in specific cAMP hydrolyzing activity. The aim of the present study was to investigate the role of the cyclic phosphodiesterase type 4 (PDE4) in human lung and to determine the effects of NCS 613, a new PDE4 inhibitor, on lung inflammation and bronchial hyperresponsiveness. High cAMP-PDE activities were found in the cytosoluble fractions from human lung parenchyma and distal bronchi. PDE4 (rolipram sensitive) represented 40% and 56% of total cAMP-PDE activities in the above-corresponding tissues. Moreover, PDE4A, PDE4B, PDE4C, and PDE4D isoforms were detected in all three subcellular fractions (cytosolic, microsomal, and nuclear) with differential distributions according to specific variants. Pharmacological treatments with NCS 613 significantly decreased PDE4 activity and reduced IκBα degradation in cultured parenchyma, both of which are usually correlated with a lower inflammation status. Moreover, NCS 613 pretreatment potentiated isoproterenol-induced relaxations in human distal bronchi, while reducing TNF-α-induced hyperresponsiveness in cultured bronchi, as assessed in the presence of methacholine, U-46619, or histamine. This reducing effect of NCS 613 on human bronchi hyperresponsiveness triggered by TNF-α was related to a lower expression level of PDE4B and PDE4C, as well as a downregulation of the phosphorylated forms of p38-MAPK, CPI-17, and MYPT-1, which are known to control tone. In conclusion, specific PDE4 inhibitors, such as NCS 613, may represent an alternative and isoform-specific approach toward reducing human lung inflammation and airway overreactivity.

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In cardiac myocytes, cAMP elevation triggers the down-regulation of transcripts and promoter activity for cyclic AMP phosphodiesterase-4A10 (PDE4A10)

Cited by 17 publications

References 89 publications

Phosphodiesterase (PDE) inhibitor torbafylline (HWA 448) attenuates burn-induced rat skeletal muscle proteolysis through the PDE4/cAMP/EPAC/PI3K/Akt pathway

Phosphodiesterase (PDE) inhibitor torbafylline (HWA 448) attenuates burn-induced rat skeletal muscle proteolysis through the PDE4/cAMP/EPAC/PI3K/Akt pathway

Cyclic nucleotide phosphodiesterase profiling reveals increased expression of phosphodiesterase 7B in chronic lymphocytic leukemia

NCS 613, a potent and specific PDE4 inhibitor, displays anti-inflammatory effects on human lung tissues

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