Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Journal of Molecular and Cellular Cardiology |
| Vol/bind | 40 |
| Udgave nummer | 6 |
| Sider (fra-til) | 790-8 |
| Antal sider | 8 |
| ISSN | 0022-2828 |
| DOI | |
| Status | Udgivet - 2006 |
Bibliografisk note
Keywords: Amino Acid Sequence; Animals; Connexin 43; Heart Arrest; Male; Molecular Sequence Data; Myocardial Ischemia; Oligopeptides; Phosphorylation; Phosphotransferases; Rats; Rats, Sprague-Dawley; SerineAdgang til dokumentet
Citationsformater
- APA
- Standard
- Harvard
- Vancouver
- Author
- BIBTEX
- RIS
Identification of ischemia-regulated phosphorylation sites in connexin43: A possible target for the antiarrhythmic peptide analogue rotigaptide (ZP123). / Axelsen, Lene Nygaard; Stahlhut, Martin; Mohammed, Shabaz; Larsen, Bjarne Due; Nielsen, Morten S; Andersen, Søren; Jensen, Ole N; Hennan, James K; Kjølbye, Anne Louise; Holstein-Rathlou, N.-H.
I: Journal of Molecular and Cellular Cardiology, Bind 40, Nr. 6, 2006, s. 790-8.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
}
TY - JOUR
T1 - Identification of ischemia-regulated phosphorylation sites in connexin43: A possible target for the antiarrhythmic peptide analogue rotigaptide (ZP123).
AU - Axelsen, Lene Nygaard
AU - Stahlhut, Martin
AU - Mohammed, Shabaz
AU - Larsen, Bjarne Due
AU - Nielsen, Morten S
AU - Andersen, Søren
AU - Jensen, Ole N
AU - Hennan, James K
AU - Kjølbye, Anne Louise
AU - Holstein-Rathlou, N.-H.
N1 - Keywords: Amino Acid Sequence; Animals; Connexin 43; Heart Arrest; Male; Molecular Sequence Data; Myocardial Ischemia; Oligopeptides; Phosphorylation; Phosphotransferases; Rats; Rats, Sprague-Dawley; Serine
PY - 2006
Y1 - 2006
N2 - Previous studies suggest that dephosphorylation of connexin43 (Cx43) is related to uncoupling of gap junction communication, which plays an important role in the genesis of ischemia-induced ventricular tachycardia. We studied changes in Cx43 phosphorylation during global ischemia in the absence and presence of the antiarrhythmic peptide analogue rotigaptide (formerly known as ZP123). Phosphorylation analysis was performed on Cx43 purified from isolated perfused rat hearts using matrix-assisted laser desorption/ionization mass spectrometry and liquid chromatography electrospray ionization tandem mass spectrometry. Thirteen different serine phosphorylation sites were identified in Cx43 during non-ischemic conditions, three of which had not previously been described. Within the first 7 min of ischemia, Ser306 became fully dephosphorylated whereas Ser330 became phosphorylated. Between 15 and 30 min of ischemia, the critical time interval where gap junction uncoupling occurs, Ser297 and Ser368 also became fully dephosphorylated. During the same time period, all untreated hearts developed asystole. Treatment with rotigaptide significantly increased the time to ischemia-induced asystole and suppressed dephosphorylation of Ser297 and Ser368 at 30 min of ischemia. Our results suggest that phosphorylation of Ser297 and Ser368 may be involved in functional gating of Cx43 during ischemia and may be possible downstream targets for rotigaptide signaling.
AB - Previous studies suggest that dephosphorylation of connexin43 (Cx43) is related to uncoupling of gap junction communication, which plays an important role in the genesis of ischemia-induced ventricular tachycardia. We studied changes in Cx43 phosphorylation during global ischemia in the absence and presence of the antiarrhythmic peptide analogue rotigaptide (formerly known as ZP123). Phosphorylation analysis was performed on Cx43 purified from isolated perfused rat hearts using matrix-assisted laser desorption/ionization mass spectrometry and liquid chromatography electrospray ionization tandem mass spectrometry. Thirteen different serine phosphorylation sites were identified in Cx43 during non-ischemic conditions, three of which had not previously been described. Within the first 7 min of ischemia, Ser306 became fully dephosphorylated whereas Ser330 became phosphorylated. Between 15 and 30 min of ischemia, the critical time interval where gap junction uncoupling occurs, Ser297 and Ser368 also became fully dephosphorylated. During the same time period, all untreated hearts developed asystole. Treatment with rotigaptide significantly increased the time to ischemia-induced asystole and suppressed dephosphorylation of Ser297 and Ser368 at 30 min of ischemia. Our results suggest that phosphorylation of Ser297 and Ser368 may be involved in functional gating of Cx43 during ischemia and may be possible downstream targets for rotigaptide signaling.
U2 - 10.1016/j.yjmcc.2006.03.005
DO - 10.1016/j.yjmcc.2006.03.005
M3 - Journal article
C2 - 16678851
VL - 40
SP - 790
EP - 798
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
SN - 0022-2828
IS - 6
ER -