cCMP and cUMP in Apoptosis: Concepts and Methods.

Abstract	The cyclic nucleotides cAMP and cGMP are well-characterized second messenger molecules regulating many important intracellular processes, such as differentiation, proliferation, and apoptosis. The latter is a highly regulated process of programmed cell death wherein several regulatory proteins, like those belonging to the Bcl-2 family, are involved. The initiation of apoptosis is regulated by three different pathways: the intrinsic or mitochondrial, the extrinsic, and the ER stress pathway. Recently, it has been published that the pyrimidine cyclic nucleotides cCMP and cUMP also function as second messenger molecules, and additionally have an effect on apoptosis signaling pathways. cCMP induced PKA-independent apoptosis via the intrinsic and ER-stress pathway in S49 mouse lymphoma cells, and cCMP as well as cUMP induced apoptosis in human HEL cells via the intrinsic pathway. However, in human K-562 cells, which are known to be multidrug-resistant, cCMP and cUMP had no effect. Summarized in this chapter are the initiation of apoptosis by cCMP and cUMP regarding the various apoptotic pathways, the enzymes involved in apoptosis, as well as the most relevant methods for the detection and examination of apoptosis and the corresponding signaling pathways.
Authors	Sabine Wolter, Fanni Dittmar, Roland Seifert
Journal	Handbook of experimental pharmacology (Handb Exp Pharmacol) Vol. 238 Pg. 25-47 ( 2017) ISSN: 0171-2004 [Print] Germany
PMID	28456891 (Publication Type: Journal Article, Review)
Chemical References	Nucleotides, Cyclic Cyclic CMP cyclic 3',5'-uridine monophosphate Cyclic AMP Uridine Monophosphate Cyclic AMP-Dependent Protein Kinases ADCY10 protein, human Adenylyl Cyclases Soluble Guanylyl Cyclase Cyclic GMP
Topics	Adenylyl Cyclases (metabolism) Animals Apoptosis Biological Assay (methods) Blotting, Western Cell Cycle Cell Line Cell Proliferation Cyclic AMP (metabolism) Cyclic AMP-Dependent Protein Kinases (metabolism) Cyclic CMP (metabolism) Cyclic GMP (metabolism) Flow Cytometry Fluorometry Humans Membrane Potential, Mitochondrial Nucleotides, Cyclic (metabolism) Second Messenger Systems Soluble Guanylyl Cyclase (metabolism) Uridine Monophosphate (metabolism)

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