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Regulation and function of cyclic nucleotide phosphodiesterases in pathological vascular remodeling

中国药理学与毒理学杂志 2017年第5期31卷 456-457页

作者： YAN Chen Aab Cardiovascular Research Institute University of Rochester

Pathological vascular remodeling is characterized by thickening or thinning of the vessel wall through altering cellular and non-cellular components,which associates with various blood circulation disorders in brain,heart,lung,and peripheral vasculatures. Pathological vascular remodeling occurs in response to a variety of vascular insults such as mechanical(angioplasty or stenting) or biological(lipids,diabetes,smoking,or virus) injuries. It is a polygenic process involving multiple cell types in the vessel wall or circulation,including endothelial cells(ECs),smooth muscle cells(SMCs),fibroblasts,leukocytes,and platelets. One of hallmarks is the transition of vascular smooth muscle cells(SMCs)from a differentiated/quiescent contractile phenotype to a myofibroblast-like dedifferentiated/active so-called synthetic phenotype. Synthetic SMCs are proliferatory,migratory,secretory and inflammatory,playing key roles in the pathogenesis of vascular remodeling. In the normal vessel,ECs synthesize and secrete biological substances such as prostacyclins(PGI_2) and nitric oxide(NO) that not only function as vasodilators but also inhibit SMC phenotype transition and other properties associated with the synthetic phenotype. Cyclic nucleotides cAMP and cGMP are primary mediators of PGI_2 and NO,respectively,and play critical roles in control vascular structural integrity and function. Cyclic nucleotides are controlled by selective activation or inhibition of distinct cyclic nucleotide phosphodiesterase(PDE) isozymes catalyzing the degradation reaction. To date,more than 60 different PDE isoenzymes derived from 22 genes are identified and grouped into 11 broad families(PDE1-PDE11). PDEs are expressed in a cell/tissue-specific manner and only a few enzymes are expressed in any single cell type. Through systematic assessment of the expression levels of all known PDE isoforms in contractile versus synthetic SMCs,we found that the expression levels of a number of PDE are significantly

关键词： phosphodiesterases smooth muscle cells vascular remodeling

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Targeting phosphodiesterases for cognition enhancement:a translational approach

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中国药理学与毒理学杂志 2017年第5期31卷 453-454页

作者： Jos PRICKAERTS Department of Psychiatry and Neuropsychology School for Mental Health and NeuroscienceMaastricht University

Cyclic adenosine monophosphate(cA MP) and/or cyclic guanosine monophosphate(cG MP)have been suggested to play specific roles in processes of memory. These cyclic nucleotides are hydrolyzed by specific enzymes,ie phosphodiesterases(PDEs). Thus,selective PDE inhibitors preventing the breakdown of cAMP and/or cGMP could improve memory. Studies with different timing of treatment with specific PDE inhibitors indicated that distinct underlying signaling pathways for early and late consolidation processes exist corresponding to specific time-windows for memory consolidation into longterm memory. There is evidence that the underlying mechanisms of PDE inhibition on the observed behavioral effects are independent of possible cerebrovascular effects. Most likely the underlying mechanisms are a cGMP/PKG pathway for early consolidation processes and a cAMP/PKA pathway for late consolidation processes. In addition,the early-phase cG MP/PKG signaling actually requires late-phase cAMP/PKA-signaling in long-term memory formation. Recently,the effects of specific PDE inhibitors are explored on other cognitive domains including acquisition processes/short-term memory and information processing. It will be shown that elevation of central cG MP levels or cA MP levels after treatment with a specific PDE inhibitor both improve acquisition processes/short-term memory. In vitro studying the effects of PDE inhibitors on long-term potentiation,the physiological substrate of memory,supportthe in vivo data and further show that AMPA receptor trafficking very likely mediates the memory enhancing effects. In a translational approach we initially also investigated the effects of cG MP elevation via PDE5 inhibition with vardenafil or sildenafil on cognition in humans. However,in contrast to studies with rodents and monkeys,PDE5 inhibition had no effect in humans on cognition including memory processes. It is clear that the transition of a drug from preclinical to clinical creates translational hur

关键词： phosphodiesterases cognition memory

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Identification of two glycerophosphodiester phosphodiesterase genes in maize leaf phosphorus remobilization

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The Crop Journal 2021年第1期9卷 95-108页

作者： Jingxin Wang Wenbo Pan Alexiy Nikiforov William King Wanting Hong Weiwei Li Yang Han Jana Patton-Vogt Jianbo Shen Lingyun Cheng Key Laboratory of Plant-Soil Interactions Ministry of Education/Key Laboratory of Plant NutritionMinistry of AgricultureDepartment of Plant NutritionChina Agricultural UniversityBeijing 100193China State Key Laboratory of Plant Genomics Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China Department of Biological Sciences Duquesne UniversityPittsburghPA 15282USA

Phosphate deficiency is one of the leading causes of crop productivity *** degradation liberates phosphate to cope with phosphate *** phosphodiesterases(GPX-PDEs)hydrolyse the intermediate products of phospholipid catabolism glycerophosphodiesters into glycerol-3-phosphate,a precursor of ***,the function of GPX-PDEs in phosphate remobilization in maize remains *** the present study,we characterized two phosphate deficiency-inducible GPX-PDE genes,ZmGPX-PDE1 and ZmGPX-PDE5,in maize ***-PDE1 and ZmGPX-PDE5 were transcriptionally regulated by ZmPHR1,a well-described phosphate starvation-responsive transcription factor of the MYB *** of the yeast GPX-PDE mutant gde1Δindicated that ZmGPX-PDE1 and ZmGPX-PDE5 functioned as GPX-PDEs,suggesting their roles in phosphate recycling from *** vitro enzyme assays showed that ZmGPX-PDE1 and ZmGPX-PDE5 catalysed glycerophosphodiester degradation with different substrate preferences for glycerophosphoinositol and glycerophosphocholine,***-PDE1 was upregulated during leaf senescence,and more remarkably,loss of ZmGPXPDE1 inmaize compromised the remobilization of phosphorus fromsenescing leaves to young leaves,resulting in a stay-green phenotype under phosphate *** results suggest that ZmGPX-PDE1 catalyses the degradation of glycerophosphodiesters in maize,promoting phosphate recycling from senescing leaves to new *** mechanism is crucial for improving phosphorus utilization efficiency in crops.

关键词： Glycerophosphodiester phosphodiesterases Maize Phosphate deficiency Phosphorus remobilization Phospholipid

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Regulation by phosphodiesterase of anxiety-and depressive-like behavior induced by alcohol withdrawal in mice

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中国药理学与毒理学杂志 2021年第9期35卷 667-668页

作者： LIU Xiao-qian WANG Dong ZHENG Wen-qing ZHANG Fang-fang ZHANG Han-ting Institute of Pharmacology Shandong First Medi-cal University&Shandong Academy of SciencesTai’an 271016China Department of Pharma-cology Qingdao University School of PharmacyQingdao 266073China

OBJECTIVE Alcohol dependence is not only the most common public health prob⁃lem worldwide,but also the cause of many alco⁃hol-related diseases,such as anxiety and depres⁃***,the mechanism of these comor⁃bidities is not ***,the role of phos⁃phodiesterases(PDEs)in anxiety-and depres⁃sion-like behavior induced by alcohol withdrawal has received increasing *** are a superfamily of enzymes that catalyze the hydroly⁃sis of intracellular cyclic AMP(cAMP)and(or)cyclic GMP(cGMP).There are 11 families(PDE1-PDE11),each of which has 1 to 4 sub⁃types encoded by different *** the present study,we identified the key PDEs involved in anxiety-and depression-like behavior induced by alcohol *** After withdrawal from short-term or chronic intermittent ethanol vapor exposure(STEVE and CIEVE,respectively),adult male C57BL/6J(B6)mice were tested for anxiety-and depression-like behavior using the sucrose preference,open field,elevated plus-maze,tail suspension,forced swimming,hole board and light-dark *** addition,the expression of PDE subtypes(PDE2,PDE4,and PDE7)in the hippocampus,amygdala,and stria⁃tum,which are considered as anxiety-and(or)depression-related brain regions,was detected by Western ***①Differences in anxiety-and depression-like behaviors between STEVE and CIEVE *** to STEVE mice,CIEVE mice showed greater anxiety-and depression-like behavior in the tests described above.②The expression of PDE2,PDE4 and PDE7 in the anxiety-and depression-related brain regions of CIEVE *** to the STEVE mice,CIEVE mice showed significant higher expression of PDE4A and PDE7A in the hippo⁃campus(P<0.05)and PDE4D and PDE7A in the amygdala(P<0.05).However,the expres⁃sion of PDE2A,PDE4B,PDE4D and PDE7B in the hippocampus,PDE2A,PDE4A,PDE4B and PDE7B in the amygdala,PDE2A,PDE4A,PDE4B,PDE4D,PDE7A and PDE7B in the striatum was not significantly *** The model of CIEVE showed significant anxiety-and

关键词： phosphodiesterases alcohol with⁃drawal behavior

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Cyclic nucleotide phosphodiesterase 3B is connected to osteopontin and protein kinase CK2 in pancreatic <i>β</i>-cells

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Journal of Biomedical Science and Engineering 2013年第5期6卷 73-84页

作者： Emilia Heimann Amitabh Sharma Nalini Raghavachari Vincent C. Manganiello Lena Stenson Eva Degerman Center for Complex Network Research (CCNR) Department of Physics Northeastern University Boston USA Department of Experimental Medical Science Division for Diabetes Metabolism and Endocrinology Lund University Lund Sweden DNA Sequencing and Genomics Core Genetics and Development Biology Center Pulmonary/Critical Care Medicine Branch National Heart Lung and Blood Institute National Institutes of Health (NIH) Bethesda USA

Islets from RIP-PDE3B mice, exhibiting β-cell specific overexpression of the cAMP/cGMP-degrading enzyme phosphodiesterase 3B (PDE3B) and dysregulated insulin secretion, were subjected to microarray analysis. We show that osteopontin (OPN) mRNA is increased in a dose-dependent manner in islets from RIP-PDE3B mice, as compared to wild-type islets. In addition, in silico analysis shows that PDE3B and OPN are interacting. Furthermore, OPN interacts with protein kinase CK2 ina distinct submodule of the protein-protein interaction network. We studied PDE3B and OPN proteins and, in some cases, also PDE1B and PDE4C, under conditions of relevance for insulin secretion. In the presence of forskolin, PDE inhibitors, insulin, or a protein kinase CK2 inhibitor, similar alterations in protein levels of PDE3B and OPN are shown. In summary, results from using a number of strategies demonstrate a connection between PDE3B and OPNas well as a role for protein kinase CK2 inpancreatic β-cells.

关键词： Diabetes Mellitus Pancreatic Islets β-Cells cAMP Cyclic Nucleotide phosphodiesterases PDE Osteopontin Protein Kinase CK2

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