title: CREB modulates calcium signaling in cAMP-induced bone marrow stromal cells (BMSCs).
abstract: Calcium signaling has a versatile role in many important cellular functions. Despite its importance, regulation of calcium signaling in bone marrow stromal cells (BMSCs, also known as bone marrow-derived mesenchymal stem cells) has not been explored extensively. Our previous study revealed that cyclic adenosine monophosphate (cAMP) enabled BMSCs to generate calcium signal upon stimulation by dopamine, KCl and glutamate. Concurrently, cAMP transiently activated the transcription factor cAMP response element binding protein (CREB) in BMSCs. Activity of CREB can be modulated by the calcium/calmodulin-dependent kinase signaling pathway, however, whether the calcium signaling observed in cAMP-induced BMSCs requires CREB has not been investigated. In an effort to uncover the role of CREB in the generation of calcium signaling in response to modulators such as dopamine and KCl, we knocked down CREB activity in BMSCs. Our study indicated that BMSCs, but not its close relative fibroblasts, are responsive to dopamine and KCl after cAMP treatment. Calcium signal elicited by dopamine depends, in part, on calcium influx whereas that elicited by KCl depends completely on calcium influx. Knock-down of CREB activity significantly reduced or abolished the cAMP-induced calcium response, and reintroducing a constitutively active CREB partially restored the calcium response.
authors.affiliation: Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI 48824, United States.
authors.forename: Linxia
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, United States.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Cellular and Molecular Biology Program, Michigan State University, East Lansing, MI 48824, United States.
authors.forename: Ryan
authors.initials: R
authors.lastname: Thompson
authors.affiliation: Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI 48824, United States; Department of Computer Science and Engineering, Michigan State University, East Lansing, MI 48824, United States. Electronic address: krischan@egr.msu.edu.
authors.forename: Christina
authors.initials: C
authors.lastname: Chan
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D005260:Female; D055785:Gene Knockdown Techniques / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D010766:Phosphorylation; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D000242:Cyclic AMP; D002118:Calcium
keywords: Bone marrow stromal cells; CREB; Calcium signal; Morphology