Phosphorylation status of matrix metalloproteinase 2 in myocardial ischaemia–reperfusion injury
| Autor: | Charles F.B. Holmes, Richard Schulz, Meltem Sariahmetoglu, Monika Skrzypiec-Spring, Nermeen Youssef, Anna L.B. Jacob-Ferreira, Grzegorz Sawicki, Jolanta Sawicka |
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| Rok vydání: | 2012 |
| Předmět: |
Male
medicine.medical_specialty Ischemia Myocardial Reperfusion Injury Rats Sprague-Dawley Dephosphorylation Protein Phosphatase 1 Internal medicine Okadaic Acid Troponin I medicine Animals Protein Phosphatase 2 Enzyme Inhibitors Phosphorylation business.industry Myocardium Heart Protein phosphatase 1 Protein phosphatase 2 Alkaline Phosphatase medicine.disease Rats Surgery Endocrinology Matrix Metalloproteinase 2 Alkaline phosphatase Cardiology and Cardiovascular Medicine business Reperfusion injury |
| Zdroj: | Heart. 98:656-662 |
| ISSN: | 1468-201X 1355-6037 |
| Popis: | Objective To investigate whether alterations in the phosphorylation status of matrix metalloproteinase 2 (MMP-2) in the heart may be protective in the setting of ischaemia–reperfusion (IR) injury. Design In-vitro heart function and biochemical research study. Setting University basic science laboratory. Interventions Male Sprague–Dawley rats, weighing 250–350 g. Isolated rat hearts were perfused at constant pressure either aerobically for 75 min or subjected to 20 min of global, no-flow ischaemia followed by 30 min of reperfusion. Main Outcome Measures Heart mechanical function, MMP-2 activity and troponin I levels. Results The serine/threonine phosphatase inhibitor okadaic acid (OA) improved the recovery of mechanical function compared with control IR hearts and prevented the loss of troponin I. OA significantly reduced protein phosphatase 2A, but not protein phosphatase 1, activity in perfused hearts. IR stimulated the activation and release of MMP-2 into the coronary effluent in the first 2 min of reperfusion. This was accompanied by a decrease in the remaining activity and protein level of MMP-2 in heart tissue determined at the end of the reperfusion. OA did not alter the IR-stimulated release of MMP-2 into the coronary effluent, but reduced the decrease in MMP-2 in reperfused hearts. The immunoprecipitation of heart homogenates using anti-phosphoserine antibody showed that MMP-2 is phosphorylated. The dephosphorylation of MMP-2 by alkaline phosphatase treatment of homogenates prepared from IR hearts treated with OA significantly increased MMP-2 activity. Conclusions These results suggest that the phosphorylation status of MMP-2 is important in its contribution to myocardial IR injury. |
| Databáze: | OpenAIRE |
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