2015年5月1日 · We show that PDE4 activation by UCR1C prevents isoproterenol-induced cardiomyocyte hypertrophy. We define the mechanism by which UCR1C modulates hypertrophic cAMP-PKA signaling. We propose PDE4 activation as a potential therapeutic strategy in treating heart failure. Hypertrophy increases the risk of heart failure and arrhythmia.

2022年7月1日 · Taken together, α-mangostin derivative 4e, a PDE4 inhibitor, efficiently activated the cAMP/PKA pathway in neuronal cells, and promoted UPS activity as evidenced by enhanced degradation of UPS substrate Ub-G76V-GFP and Ub-R-GFP, as well as elevated proteasomal enzyme activity.

基于 α-mangostin 的基于结构的优化产生了一种有效的 PDE4 抑制剂 4e。 进行 cAMP 测定以量化样品中的 cAMP 水平。 模型 UPS 底物（Ub-G76V-GFP 和 Ub-R-GFP）用于监测 UPS 依赖性活动。 通过短肽底物 Suc-LLVY-AMC 研究蛋白酶体活性，蛋白酶体对其的切割增加了荧光敏感性。 Tet-on WT、A30P 和 A53T α-syn 诱导型 PC12 细胞和来自 A53T 转基因小鼠的原代小鼠皮质神经元用于评估 4e 在体外对 α-syn 的 作用。 杂合 A53T 转基因小鼠用于评估 4e 对 体内 α-syn 清 …

PDE4 proteins are distinguished from other PDEs by their high selectivity for cAMP over cGMP as substrate and their sensitivity to inhibition by the prototypal PDE4 inhibitor rolipram. Each of the PDE4 genes is expressed as multiple variants via alternative splicing and use of alternate promoters/transcription start sites.

Consistent with the biological effect of other PDE4 and PDE7 inhibitors, BC54 displays potent anti-inflammatory properties and is superior to a combination of rolipram (a PDE4 inhibitor) and BRL50481 (a PDE7A inhibitor) for inducing apoptosis in chronic lymphocytic leukemia (CLL) cells.

Results: Taken together, α-mangostin derivative 4e, a PDE4 inhibitor, efficiently activated the cAMP/PKA pathway in neuronal cells, and promoted UPS activity as evidenced by enhanced degradation of UPS substrate Ub-G76V-GFP and Ub-R-GFP, as well as elevated proteasomal enzyme activity.

2016年9月5日 · Our results show that ECM-dependent differential inflammatory signalling is due to an interaction of the α5 cytoplasmic domain with the cAMP-specific phosphodiesterase PDE4D5, with consequent...

In this study, we found that if an N-terminal hydrophobic domain of ApPDE4 short-form is linked to the GFP-fused PH domain of OSBP, OSH1, and FAPP1, these proteins were localized to the plasma membrane as well as the TGN.

流式分选 Mϕ 的 RNA-seq 分析将磷酸二酯酶 4b (PDE4b) 鉴定为顶级 LPS 响应 cAMP 调节基因。 我们观察到 PDE4b 表达在损伤高峰时（4 小时）显着增加，然后在消退阶段（24 小时）降低至基础水平以下。 Mφ 中 PDE4b 的转录需要激活转录因子 NFATc2。 在损伤高峰时抑制 PDE4 活性，使用咯利普兰，增加了 cAMP 水平，增加了修复性 AMφ 池，并解决了肺损伤。 在单核细胞条件性耗竭后没有看到这种反应，因此建立了空域招募的 PDE4b 敏感单核细胞作为修复性 AMφ …

2023年4月19日 · The PDE4 inhibitor 4e derivative of α-mangostin (phytoconstituent) promoted UPS activity, which was evident by the accelerated degradation of the UPS substrates Ub-G76V-GFP and Ub-R-GFP, as well as increased proteasomal enzyme activity (Chen et al. 2022). Treatment with this derivative reduced α-synuclein accumulation in the transgenic A53T ...