Tuesday, 21 November 2017
METABOLIC EXPERIMENTAL PATHOLOGY UNIT  

 

 

 1. - Cyclooxygenase (COX) is the enzyme that catalyzes the rate limiting step in the synthesis of prostanoids. Prostaglandins play an important role in many biological processes such as platelet aggregation, maintenance of the gastric mucosa, and reproductive success. and also in pathological conditions such as inflammation and cancer. COX-2 is expressed in ischemic myocardium and in dilated cardiomyopathy, but not in a healthy heart. To clarify the role of COX-2 in the heart, have developed transgenic mice that constitutively express the enzyme in human functional cardiomyocytes under the control of the promoter of the heavy chain alpha-Myosin. These animals are protected from ischemia / reperfusion (I / R) in isolated heart with increased functional recovery and decreased cell necrosis. To further phenotype in our animal model we carried out a differential proteome analysis of cardiomyocytes, identifying a number of differentially regulated proteins by overexpression of COX-2. We have grouped these proteins according to their biological function and we have observed that many of them are mitochondrial proteins. Our results have shown an increase in the specific expression of complex IV of the respiratory chain. This correlates with higher catalytic activity of cytochrome c oxidase (CcO) measured by three independent methods (polarography, enzymology and the spectrum of cytochrome Aa3). These data show a new link between COX-2 and mitochondria could explain the protective effect of overexpression of COX-2 against injury by I / R. Our aim is to assess mitochondrial function in animal and cell models by overexpression of COX-2 to elucidate the molecular mechanism regulating the prostaglandin-dependent mitochondrial function and, thus, how to exert a cardioprotective effect.

 

2. - We maintain an ongoing collaboration in the group of Dr. Martin-Sanz del IIB whose purpose is to elucidate the role of COX-2 in the liver. Our objective here is to study the relationship between COX-2 and the inflammatory component of the disease, nonalcoholic fatty liver disease, NAFLD. We will contribute to study the contribution of prostaglandins COX-2 dependent on the development of NASH in murine models.

 

 Principal Investigator:

 Marta Casado

 
 
Currículum Vitae

Publications

Teléfono: 963393778

Email: mcasadoibv.csic.es 

 
 
  • Casado , Marta
  • Cucarella Tormo , Carme