Molecular Cardiology Titin is a Target of Matrix Metalloproteinase-2 Implications in Myocardial Ischemia/Reperfusion Injury
نویسندگان
چکیده
In the fall of 2006 I joined the Department of Pharmacology, University of Alberta as a PhD graduate student under the supervision of Dr. Richard Schulz. The Schulz lab studies ischemic and inflammatory heart diseases and investigates the role of specific molecules contributing to oxidative stress injury of the heart. Being in the first laboratory to discover that matrix metalloproteinase (MMP)-2 proteolyses specific proteins inside cardiomyocytes, my main project is to investigate further novel intracellular targets of MMP-2 in myocardial cell injury and/or death.
منابع مشابه
Titin is a target of matrix metalloproteinase-2: implications in myocardial ischemia/reperfusion injury.
BACKGROUND Titin is the largest mammalian (≈3000 to 4000 kDa) and myofilament protein that acts as a molecular spring in the cardiac sarcomere and determines systolic and diastolic function. Loss of titin in ischemic hearts has been reported, but the mechanism of titin degradation is not well understood. Matrix metalloproteinase-2 (MMP-2) is localized to the cardiac sarcomere and, on activation...
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BACKGROUND Matrix metalloproteinases are best recognized for their ability to degrade the extracellular matrix in both physiological and pathological conditions. However, recent findings indicate that some of them are also involved in mediating acute processes such as platelet aggregation and vascular tone. The acute contractile defect of the heart after ischemia-reperfusion may involve the pro...
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Organ damage after reperfusion of previously viable ischemic tissues is defined as ischemia/reperfusion injury. The pathophysiology of ischemia/reperfusion injury involves cellular effect of ischemia, reactive oxygen species and inflammatory cascade. Protection against ischemia/reperfusion injury may be achieved by preconditioning or postconditioning. In this review, we discuss basic mechan...
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Much is known regarding cardiac energy metabolism in ischemia/reperfusion (I/R) injury. Under aerobic conditions, the heart prefers to metabolize fatty acids, which contribute to 60-80% of the required ATP. During ischemia, anaerobic glycolysis increases and becomes an important source of ATP for preservation of ion gradients. With reperfusion, fatty acid oxidation quickly recovers and again pr...
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OBJECTIVE Matrix metalloproteinase-9 (MMP-9) activity is up regulated in the heart subjected to ischemic insult. Whether increased MMP-9 activity contributes to acute myocardial injury after ischemia-reperfusion remains unknown. To investigate the role of MMP-9 in myocardial infarction, we utilized a MMP-9 knockout mouse. METHODS AND RESULTS Standard homologous recombination in embryonic stem...
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