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SpringerLink Springer Biomedical and Life Sciences eBooks 2017 English+International

Preface; Contents; cCMP and cUMP Across the Tree of Life: From cCMP and cUMP Generators to cCMP- and cUMP-Regulated Cell Functions; 1 Introduction; 2 Overview of cAMP and cGMP Signaling; 3 cCMP and cUMP Generators; 3.1 Initial Problems and Revitalization of the Field; 3.2 Soluble Guanylyl Cyclase; 3.3 Soluble Adenylyl Cyclase; 4 Occurrence of cCMP and cUMP in Biological Systems; 5 cCMP- and cUMP-Regulated Cell Functions; 6 Conclusions and Future Perspectives; References; cCMP and cUMP in Apoptosis: Concepts and Methods; 1 Introduction.

2 Cyclic Nucleotides and Induction of Apoptotic Pathways via Membrane-Permeant cNMP-Analogs3 Function of PKA, cAMP, cGMP, and cUMP in Apoptosis; 3.1 PKA in Apoptosis; 3.2 cAMP in Apoptosis; 3.3 cGMP in Apoptosis; 4 Hitherto Known Targets of cCMP and cUMP; 5 cCMP in Cell Proliferation and Apoptosis; 5.1 Relevant Genes in Apoptosis; 5.2 Cell Cycle Analysis: G1 Arrest; 5.3 Interaction of cCMP and cUMP with Bcl-2 Family Proteins and Induction of Apoptosis; 6 Experimental Methods; 6.1 Determination of Cell Number and Cell Proliferation; 6.1.1 Cell Number: Cell Counting After Trypan Blue Staining.

3 Nucleotide Binding Sites4 Promiscuity for Nucleobases; References; The Pseudomonas aeruginosa Exoenzyme Y: A Promiscuous Nucleotidyl Cyclase Edema Factor and Virulence Determinant; 1 Introduction; 2 The Endothelial cAMP Signal as a Barrier Protective Mechanism; 3 Edema Factor: A Soluble Adenylyl Cyclase; 4 Studies on the Discovery of ExoY and Its Enzymatic Activity; 5 ExoY and Disruption of the Endothelial Cytoskeleton; 6 Discovery That ExoY Is a Guanylyl Cyclase; 7 ExoY as a Purine and Pyrimidine Cyclase.

6.1.2 Cell Proliferation: BrdU Incorporation6.1.3 Thymidine Incorporation; 6.1.4 TUNEL Assay; 6.2 Detection of Apoptosis Using Flow Cytometry; 6.2.1 Annexin V/Propidium Iodide Staining; 6.2.2 Intracellular Staining with Cytochrome c-FITC-Antibody; 6.2.3 Cell Cycle Analysis; 6.3 Determination of the Mitochondrial Membrane Potential; 6.4 Detection of Caspases by Western Blotting and Fluorometric Assays; 7 Conclusion and Further Perspectives; References; Mammalian Nucleotidyl Cyclases and Their Nucleotide Binding Sites; 1 Introduction; 2 Overall Structure of Catalytic Domains.

8 The Intracellular Function of Purine and Pyrimidine Cyclic Nucleotide Monophosphates9 Is ExoY Relevant to Disease?; 10 Evidence That ExoY Does Not Contribute to Virulence; 11 Evidence That ExoY Contributes to Virulence; 12 Summary; References; Cyclic Nucleotide Monophosphates in Plants and Plant Signaling; 1 A Brief History of Cyclic Mononucleotide Signaling in Plants; 2 Evidence for Noncanonical Cyclic Nucleotide Monophosphates in Plants; 3 Cyclic Mononucleotides and Their Role in Plant Reactive Oxygen Species (ROS) Signaling.

The cyclic purine nucleotides 3',5'-cAMP and 3',5'-cGMP are well-established second messengers. cGMP has recently been covered in a volume of the Handbook of Experimental Pharmacology (volume 191). In addition to 3',5'-cAMP and 3',5'-cGMP, so-called non-canonical cyclic nucleotides exist. These comprise the cyclic pyrimidine nucleotides 3',5'-cCMP and 3',5'-cUMP, the purine nucleotide 3',5'-cIMP, the 2',3'-nucleoside monophosphates and cyclic dinucleotides. In this volume of the Handbook of Pharmacology, word-leading experts in the field summarize our current knowledge on these non-canonical cyclic nucleotides, discuss open questions, future research directions and the pharmacotherapeutic implications. Special emphasis will be given to the emerging roles of 3',5'-cCMP and 3',5'-cUMP as second messengers with regard to generators, effectors, biological functions, inactivation and bacterial toxins. The role of 3',5'-cIMP as potential second messenger will also be critically discussed. Furthermore, we will consider transport of cyclic nucleotides and their potential role as first messengers. The role of the cyclic dinucleotide cGAMP in the immune system will covered, too. Lastly, the book will present important methodological aspects ranging from mass-spectrometric methods for cyclic nucleotide detection to the synthesis of nucleotide analogs as experimental tools and holistic methods for analysis of cyclic nucleotide effects.