Article date: June 2005
By: Rebecca H Ritchie, Jennifer M Gordon, Owen L Woodman, Anh H Cao, Gregory J Dusting in Volume 145, Issue 4, pages 495-502
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‐12–26, preserves contractile function of cardiac muscle in vitro. The aim of the present study was to determine if Anx‐12–26 elicits protective actions specifically on the cardiac myocyte (in the absence of neutrophils), using a model of metabolic inhibition to simulate ischaemia.
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±7 IU L−1 (both n=40, P<0.001), respectively. However, cellular injury was significantly decreased when Anx‐12–26 (0.3 μM) was present during metabolic inhibition, CK by 74±10% and LDH by 71±6% (both n=31, P<0.001), respectively.
Boc 2 (10 μM), a nonselective formyl peptide receptor antagonist, present during metabolic inhibition, abolished the cardioprotective effect of Anx‐12–26.
Addition of chelerythrine (10 μM), 5‐hydroxydecanoate (500 μM) or SB202190 (1 μM) during metabolic inhibition also abolished Anx‐12–26‐induced cardioprotection.
Cellular injury induced by metabolic inhibition was also largely prevented when myocytes were incubated with Anx‐12–26 for 5 min with 10 min recovery prior to the insult, or when Anx‐12–26 was present only during the recovery period following drug‐free metabolic inhibition.
In conclusion, the annexin‐1 peptide Anx‐12–26 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.
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‐12–26, preserves contractile function of cardiac muscle in vitro. The aim of the present study was to determine if Anx‐12–26 elicits protective actions specifically on the cardiac myocyte (in the absence of neutrophils), using a model of metabolic inhibition to simulate ischaemia.
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±7 IU L−1 (both n=40, P<0.001), respectively. However, cellular injury was significantly decreased when Anx‐12–26 (0.3 μM) was present during metabolic inhibition, CK by 74±10% and LDH by 71±6% (both n=31, P<0.001), respectively.
Boc 2 (10 μM), a nonselective formyl peptide receptor antagonist, present during metabolic inhibition, abolished the cardioprotective effect of Anx‐12–26.
Addition of chelerythrine (10 μM), 5‐hydroxydecanoate (500 μM) or SB202190 (1 μM) during metabolic inhibition also abolished Anx‐12–26‐induced cardioprotection.
Cellular injury induced by metabolic inhibition was also largely prevented when myocytes were incubated with Anx‐12–26 for 5 min with 10 min recovery prior to the insult, or when Anx‐12–26 was present only during the recovery period following drug‐free metabolic inhibition.
In conclusion, the annexin‐1 peptide Anx‐12–26 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.
British Journal of Pharmacology (2005) 145, 495–502. doi:10.1038/sj.bjp.0706211
DOI: 10.1038/sj.bjp.0706211
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