TY - JOUR
T1 - Annexin-1 peptide Anx-1 2-26 protects adult rat cardiac myocytes from cellular injury induced by simulated ischaemia
AU - Ritchie, Rebecca H.
AU - Gordon, Jennifer M.
AU - Woodman, Owen L.
AU - Cao, Anh H.
AU - Dusting, Gregory J.
PY - 2005/6/1
Y1 - 2005/6/1
N2 - The anti-inflammatory properties of annexin-1 peptides have been largely ascribed to their powerful antineutrophil actions in vivo. We have recently reported that the N-terminal fragment of annexin-1, Anx-1 2-26, preserves contractile function of cardiac muscle in vitro. The aim of the present study was to determine if Anx-1 2-26 elicits protective actions specifically on the cardiac myocyte (in the absence of neutrophils), using a model of metabolic inhibition to simulate ischaemia. 2 Metabolic inhibition of cardiac myocytes (4 h incubation at 37°C in HEPES-containing buffer supplemented with 2-deoxy-D-glucose, D,L-lactic acid and pH adjusted to 6.5) followed by 2.5 h recovery in normal medium markedly increased creatine kinase (CK) and lactate dehydrogenase (LDH) levels by 179 ± 39 and 26 ± 7IU L -1 (both n = 40, P < 0.001), respectively. However, cellular injury was significantly decreased when Anx-1 2-26 (0.3 mu;M) was present during metabolic inhibition, CK by 74 ± 10% and LDH by 71 ± 6% (both n = 31, P < 0.001), respectively. 3 Boc 2 (10 μM), a nonselective formyl peptide receptor antagonist, present during metabolic inhibition, abolished the cardioprotective effect of Anx-1 2-26. 4 Addition of chelerythrine (10 μM), 5-hydroxydecanoate (500 μM) or SB202190 (1 μM) during metabolic inhibition also abolished Anx-1 2-26- induced cardioprotection. 5 Cellular injury induced by metabolic inhibition was also largely prevented when myocytes were incubated with Anx-1 2-26 for 5 min with 10 min recovery prior to the insult, or when Anx-1 2-26 was present only during the recovery period following drug-free metabolic inhibition. 6 In conclusion, the annexin-1 peptide Anx-1 2-26 potently prevents cardiac myocyte injury induced by metabolic inhibition, an action that was dependent at least in part on the activation of the formyl peptide receptor family of G-protein-coupled receptors, protein kinase C, p38 mitogen-activated protein kinase and ATP-sensitive potassium channels.
AB - The anti-inflammatory properties of annexin-1 peptides have been largely ascribed to their powerful antineutrophil actions in vivo. We have recently reported that the N-terminal fragment of annexin-1, Anx-1 2-26, preserves contractile function of cardiac muscle in vitro. The aim of the present study was to determine if Anx-1 2-26 elicits protective actions specifically on the cardiac myocyte (in the absence of neutrophils), using a model of metabolic inhibition to simulate ischaemia. 2 Metabolic inhibition of cardiac myocytes (4 h incubation at 37°C in HEPES-containing buffer supplemented with 2-deoxy-D-glucose, D,L-lactic acid and pH adjusted to 6.5) followed by 2.5 h recovery in normal medium markedly increased creatine kinase (CK) and lactate dehydrogenase (LDH) levels by 179 ± 39 and 26 ± 7IU L -1 (both n = 40, P < 0.001), respectively. However, cellular injury was significantly decreased when Anx-1 2-26 (0.3 mu;M) was present during metabolic inhibition, CK by 74 ± 10% and LDH by 71 ± 6% (both n = 31, P < 0.001), respectively. 3 Boc 2 (10 μM), a nonselective formyl peptide receptor antagonist, present during metabolic inhibition, abolished the cardioprotective effect of Anx-1 2-26. 4 Addition of chelerythrine (10 μM), 5-hydroxydecanoate (500 μM) or SB202190 (1 μM) during metabolic inhibition also abolished Anx-1 2-26- induced cardioprotection. 5 Cellular injury induced by metabolic inhibition was also largely prevented when myocytes were incubated with Anx-1 2-26 for 5 min with 10 min recovery prior to the insult, or when Anx-1 2-26 was present only during the recovery period following drug-free metabolic inhibition. 6 In conclusion, the annexin-1 peptide Anx-1 2-26 potently prevents cardiac myocyte injury induced by metabolic inhibition, an action that was dependent at least in part on the activation of the formyl peptide receptor family of G-protein-coupled receptors, protein kinase C, p38 mitogen-activated protein kinase and ATP-sensitive potassium channels.
KW - Annexin-1
KW - Cardioprotection
KW - Formyl peptide receptor
KW - Lipocortin-1
KW - Protein kinase C
UR - http://www.scopus.com/inward/record.url?scp=22044449219&partnerID=8YFLogxK
U2 - 10.1038/sj.bjp.0706211
DO - 10.1038/sj.bjp.0706211
M3 - Article
C2 - 15821756
AN - SCOPUS:22044449219
SN - 0007-1188
VL - 145
SP - 495
EP - 502
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 4
ER -