title: Altered Prolylcarboxypeptidase Expression and Function in Response to Different Risk Factors of Diabetes.
abstract: BACKGROUND
  Prolylcarboxypeptidase (PRCP, EC:3.4.16.2) is a cardioprotective protease. Plasma PRCP levels are elevated in type 2 diabetes (T2D) mellitus and cardiovascular diseases.
  
  
  OBJECTIVE
  Since diabetic cardiomyopathy is a late complication of uncontrolled diabetes, we tested the hypothesis that glucose and free fatty acid related risk factors for T2D mellitus and cardiovascular disease may reduce the cardioprotective property of PRCP.
  
  
  METHODS
  We examined the effects of glucose, saturated fatty acids, and unsaturated fatty acids on PRCP expression in cultured H9c2 cells as an in-vitro model for pharmacological studies. Selective inhibitors, known cardioprotective agents and saturating amounts of neutralizing antibodies were used to validate the effect of free fatty acids on the expression and function of PRCP.
  
  
  RESULTS
  The palmitate-mediated reduction of PRCP was concentration and time-dependent. Next, we explored the cardioprotective potential of thyroxin (T4) and insulin. Both T4 and insulin were able to prevent the palmitate-mediated reduction of PRCP expression in H9c2 cells. Inhibition of NF-kB with its specific inhibitor Bay 11-7082 or blockade of palmitate with polyunsaturated fatty acids was ineffective in preventing palmitate-mediated decreases in PRCP expression.
  
  
  CONCLUSIONS
  Our data indicate that elevated palmitate inhibits PRCP expression in rat cardiomyocyte. From this inference PRCP level should be monitored in obese or diabetic patients because this simple measure could identify individuals at high risk of developing health problems, such as heart failure.
authors.affiliation: Albert Einstein College of Medicine, Bronx, NY, United States.
authors.forename: Tahmineh
authors.initials: T
authors.lastname: Tabrizian
authors.affiliation: University of Mississippi, School of Pharmacy, Jackson, MS, United States.
authors.forename: Lillie
authors.initials: L
authors.lastname: Floyd
authors.affiliation: Department of Biomolecular Sciences, Division of Pharmacology, The University of Mississippi, University, MS 38677-1848, United States.
authors.forename: Zia
authors.initials: Z
authors.lastname: Shariat-Madar
mesh_terms: D000818:Animals; D002268:Carboxypeptidases / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000150:complications; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D005227:Fatty Acids / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008687:Metformin / Q000494:pharmacology; D032446:Myoblasts / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D012307:Risk Factors; D013974:Thyroxine / Q000494:pharmacology; D013997:Time Factors
chemical_list: D005227:Fatty Acids; D007328:Insulin; D008687:Metformin; D002268:Carboxypeptidases; C022448:lysosomal Pro-X carboxypeptidase; D005947:Glucose; D013974:Thyroxine
keywords: Cardiomyocyte; H9c2 cells; cardiovascular disease; diabetis; palmitate; prolylcarboxypeptidase