C-phycocyanin protects against ischemia-reperfusion injury of heart through involvement of p38 MAPK and ERK signaling.

Abstract

We previously showed that C-phycocyanin (PC), an antioxidant biliprotein pigment of Spirulina platensis (a blue-green alga), effectively inhibited doxorubicin-induced oxidative stress and apoptosis in cardiomyocytes. Here we investigated the cardioprotective effect of PC against ischemia-reperfusion (I/R)-induced myocardial injury in an isolated perfused Langendorff heart model. Rat hearts were subjected to 30 min of global ischemia at 37 degrees C followed by 45 min of reperfusion. Hearts were perfused with PC (10 microM) or Spirulina preparation (SP, 50 mg/l) for 15 min before the onset of ischemia and throughout reperfusion. After 45 min of reperfusion, untreated (control) hearts showed a significant decrease in recovery of coronary flow (44%), left ventricular developed pressure (21%), and rate-pressure product (24%), an increase in release of lactate dehydrogenase and creatine kinase in coronary effluent, significant myocardial infarction (44% of risk area), and TdT-mediated dUTP nick end label-positive apoptotic cells compared with the preischemic state. PC or SP significantly enhanced recovery of heart function and decreased infarct size, attenuated lactate dehydrogenase and creatine kinase release, and suppressed I/R-induced free radical generation. PC reversed I/R-induced activation of p38 MAPK, Bax, and caspase-3, suppression of Bcl-2, and increase in TdT-mediated dUTP nick end label-positive apoptotic cells. However, I/R also induced activation of ERK1/2, which was enhanced by PC treatment. Overall, these results for the first time showed that PC attenuated I/R-induced cardiac dysfunction through its antioxidant and antiapoptotic actions and modulation of p38 MAPK and ERK1/2.

• Authors: Mahmood Khan, Saradhadevi Varadharaj, Latha P Ganesan, Jagdish C Shobha, Madireddi U Naidu, Narasimham L Parinandi, Susheela Tridandapani, Vijay Kumar Kutala, Periannan Kuppusamy
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 290 Issue 5 Pg. H2136-45 (May 2006) ISSN: 0363-6135 [Print] United States
• PMID: 16373583 (Publication Type: Journal Article)

Chemical References

• Cardiotonic Agents
• Reactive Oxygen Species
• Phycocyanin
• Extracellular Signal-Regulated MAP Kinases
• p38 Mitogen-Activated Protein Kinases

Topics

• Animals
• Cardiotonic Agents (administration & dosage)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• MAP Kinase Signaling System (drug effects)
• Phycocyanin (administration & dosage)
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Reperfusion Injury (enzymology, pathology, prevention & control)
• Treatment Outcome
• p38 Mitogen-Activated Protein Kinases (metabolism)