更新于：2024-11-01

PDE x calcium channel x Potassium channel

更新于：2024-11-01

基本信息

关联

项与 PDE x calcium channel x Potassium channel 相关的药物

NS-3601

靶点

PDE x Potassium channel x calcium channel

作用机制

PDE inhibitors [+2]

在研机构-

原研机构

Nisshin Flour Milling Co Ltd

在研适应症-

非在研适应症

心脏病

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 PDE x calcium channel x Potassium channel 相关的临床结果

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100 项与 PDE x calcium channel x Potassium channel 相关的转化医学

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0 项与 PDE x calcium channel x Potassium channel 相关的专利（医药）

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项与 PDE x calcium channel x Potassium channel 相关的文献（医药）

2021-06-01·Molecular Genetics and Metabolism Reports4区 · 医学

Molecular basis of ventricular arrhythmogenicity in a Pgc-1α deficient murine model

4区 · 医学

ArticleOA

作者: Edling, Charlotte E ; Jeevaratnam, Kamalan ; Chadda, Karan R ; Valli, Haseeb ; Ahmad, Shiraz ; Saadeh, Khalil ; Huang, Christopher L-H ; Fazmin, Ibrahim T ; Nanthakumar, Nakulan

Mitochondrial dysfunction underlying metabolic disorders such as obesity and diabetes mellitus is strongly associated with cardiac arrhythmias. Murine Pgc-1α^-/- hearts replicate disrupted mitochondrial function and model the associated pro-arrhythmic electrophysiological abnormalities. Quantitative PCR, western blotting and histological analysis were used to investigate the molecular basis of the electrophysiological changes associated with mitochondrial dysfunction. qPCR analysis implicated downregulation of genes related to Na⁺-K⁺ ATPase activity (Atp1b1), surface Ca²⁺ entry (Cacna1c), action potential repolarisation (Kcnn1), autonomic function (Adra1d, Adcy4, Pde4d, Prkar2a), and morphological properties (Myh6, Tbx3) in murine Pgc-1α^-/- ventricles. Western blotting revealed reduced Na_V1.5 but normal Cx43 expression. Histological analysis revealed increased tissue fibrosis in the Pgc-1α^-/- ventricles. These present findings identify altered transcription amongst a strategically selected set of genes established as encoding proteins involved in cardiac electrophysiological activation and therefore potentially involved in alterations in ventricular activation and Ca²⁺ homeostasis in arrhythmic substrate associated with Pgc-1α deficiency. They complement and complete previous studies examining such expression characteristics in the atria and ventricles of Pgc-1 deficient murine hearts.

2020-05-01·Best Practice & Research Clinical Endocrinology & Metabolism2区 · 医学

Adrenocortical tumorigenesis: Lessons from genetics

2区 · 医学

Review

作者: Hannah-Shmouni, Fady ; Kamilaris, Crystal D C ; Stratakis, Constantine A

Advances in genomics over the past two decades have allowed for elucidation of the genetic alterations leading to the development of adrenocortical tumors and/or hyperplasias. These molecular changes were initially discovered through the study of rare familial tumor syndromes such as McCune-Albright Syndrome, Carney complex, Li-Fraumeni syndrome, and Beckwith-Wiedemann syndrome, with the identification of alterations in genes and molecular pathways that subsequently led to the discovery of aberrations in these or related genes and pathways in sporadic tumors. Genetic alterations in GNAS, PRKAR1A, PRKACA, PRKACB, PDE11A, and PDE8B, that lead to aberrant cyclic adenosine monophosphate-protein (cAMP) kinase A signaling, were found to play a major role in the development of benign cortisol-producing adrenocortical tumors and/or hyperplasias, whereas genetic defects in KCNJ5, ATP1A1, ATP2B3, CACNA1D, CACNA1H, and CLCN2 were implicated in the development of benign aldosterone-producing tumors and/or hyperplasias through modification of intracellular calcium signaling. Germline ARMC5 defects were found to cause the development of primary bilateral macronodular adrenocortical hyperplasia with glucocorticoid and/or mineralocorticoid oversecretion. Adrenocortical carcinoma was linked primarily to aberrant p53 signaling and/or Wnt-β-catenin signaling, as well as IGF2 overexpression, with frequent genetic alterations in TP53, ZNRF3, CTNNB1, and 11p15. This review focuses on the genetic underpinnings of benign cortisol- and aldosterone-producing adrenocortical tumors/hyperplasias and adrenocortical carcinoma.

2016-08-01·Cellular Reprogramming4区 · 医学

PDE4 Inhibition by Rolipram Promotes Neuronal Differentiation in Human Bone Marrow Mesenchymal Stem Cells

4区 · 医学

Article

作者: Cho, Goang-Won ; Joe, I-Seul

Increased intracellular cyclic adenosine monophosphate (cAMP) can promote axonal elongation and facilitate neuronal repair, while decreased cAMP is associated with losses in neuronal regenerative capacity. Rolipram, which upregulates intracellular cAMP by blocking phosphodiesterase-4 (PDE4) enzyme activity, can mitigate diverse neurological disorders. In this study, we investigated whether rolipram induces neuronal differentiation of human bone marrow-mesenchymal stem cells (hBM-MSCs). Rolipram-treated MSCs (Roli-MSCs) had significantly increased expression of the neuroprogenitor proteins Nestin, Musashi, GFAP, and Sox-2. When Roli-MSCs were differentiated with neuronal induction media (Roli-dMSCs), they exhibited cell body and dendritic morphologies similar to those of neurons. The neurite number and length of Roli-dMSCs were significantly increased compared to those of differentiated MSCs (dMSCs). Compared with undifferentiated hBM-MSCs, the Roli-dMSCs and dMSCs showed significantly increased expression of the neuronal-specific marker genes Nestin, Musashi, CD133, GFAP, NF-M, MAP-2, KCNH1, KCNH5, SCN3A, and CACNA1A, and decreased expression of other lineage-specific markers Adiponectin, ALP, FABP4, and MMP13. The Roli-dMSCs also showed a higher expression of the neuronal markers Nestin, Musashi, Sox-2, NF-M, and Tuj-1 compared to those of the undifferentiated hBM-MSCs, measured by immunocytochemistry and immunoblotting assay. Thus, we have shown that rolipram ameliorates neuronal differentiation by the regulation of neuroprogenitor expression in hBM-MSCs, and rolipram treatment of MSCs may improve the therapeutic efficacy of stem cell therapy for neurodegenerative disorders.