| Property | Value |
|---|
| Working Groups |  AG Maier |
| Subproject | A03 |
| Open Access |  Yes |
| Publication Type | Journal Article |
| Peer Reviewed | Unknown |
| PMID |  25015964 |
| DOI |  10.1152/ajpheart.00694.2013 |
| Publication Year | 2014 |
| Title | Urocortin 2 stimulates nitric oxide production in ventricular myocytes via Akt- and PKA-mediated phosphorylation of eNOS at serine 1177  |
| Journal | American Journal of Physiology-Heart and Circulatory Physiology |
| ISSN | 0363-6135 |
| eISSN | 1522-1539 |
| URL | http://ajpheart.physiology.org/content/307/5/H689 |
| Pages | H689-H700 |
| Issue | 5 |
| Volume | 307 |
| Journal Abbreviation | Am J Physiol-Heart Circul Physiol |
| Extra | Urocortin 2 (Ucn2) is a cardioactive peptide exhibiting beneficial effects in normal and failing heart. In cardiomyocytes, it elicits cAMP- and Ca2+-dependent positive inotropic and lusitropic effects. We tested the hypothesis that, in addition, Ucn2 activates cardiac nitric oxide (NO) signaling and elucidated the underlying signaling pathways and mechanisms. In isolated rabbit ventricular myocytes, Ucn2 caused concentration- and time-dependent increases in phosphorylation of Akt (Ser473, Thr308), endothelial NO synthase (eNOS) (Ser1177), and ERK1/2 (Thr202/Tyr204). ERK1/2 phosphorylation, but not Akt and eNOS phosphorylation, was suppressed by inhibition of MEK1/2. Increased Akt phosphorylation resulted in increased Akt kinase activity and was mediated by corticotropin-releasing factor 2 (CRF2) receptors (astressin-2B sensitive). Inhibition of phosphatidylinositol 3-kinase (PI3K) diminished both Akt as well as eNOS phosphorylation mediated by Ucn2. Inhibition of protein kinase A (PKA) reduced Ucn2-induced phosphorylation of eNOS but did not affect the increase in phosphorylation of Akt. Conversely, direct receptor-independent elevation of cAMP via forskolin increased phosphorylation of eNOS but not of Akt. Ucn2 increased intracellular NO concentration ([NO]i), [cGMP], [cAMP], and cell shortening. Inhibition of eNOS suppressed the increases in [NO]i and cell shortening. When both PI3K-Akt and cAMP-PKA signaling were inhibited, the Ucn2-induced increases in [NO]i and cell shortening were attenuated. Thus, in rabbit ventricular myocytes, Ucn2 causes activation of cAMP-PKA, PI3K-Akt, and MEK1/2-ERK1/2 signaling. The MEK1/2-ERK1/2 pathway is not required for stimulation of NO signaling in these cells. The other two pathways, cAMP-PKA and PI3K-Akt, converge on eNOS phosphorylation at Ser1177 and result in pronounced and sustained cellular NO production with subsequent stimulation of cGMP signaling. PMID: 25015964 |
| Authors | Walther S, Pluteanu F, Renz S, Nikonova Y, Maxwell JT, Yang LZ, Schmidt K, Edwards JN, Wakula P, Groschner K, Maier LS, Spiess J, Blatter LA, Pieske B, Kockskämper J |
| First Author | Walther S |
| Last Author | Kockskämper J |
| Scholia |  Wikidata-based representation at Scholia |
External Resources
journals...4.2013https://journals.physiology.org/doi/pdf/10.1152/ajpheart.00694.2013
Article fulltext
gro-2/32528http://resolver.sub.uni-goettingen.de/purl?gro-2/32528
GRO.publications identifier
9986https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=9986
NCBI Taxonomy (Oryctolagus cuniculus)
0000-0001-9915-4429https://orcid.org/0000-0001-9915-4429
ORCID identifier (Lars S. Maier)
04a7f6w43https://ror.org/04a7f6w43
ROR identifier (04a7f6w43, Max Planck Institute of Experimental Medicine)
021ft0n22https://ror.org/021ft0n22
ROR identifier (021ft0n22, University Medical Center Göttingen)
Q34296776https://www.wikidata.org/wiki/Q34296776
Wikidata ID
