Title:Altered Prolylcarboxypeptidase Expression and Function in Response to Different Risk Factors of Diabetes
Volume: 14
Issue: 3
Author(s): Tahmineh Tabrizian, Lillie Floyd and Zia Shariat-Madar
Affiliation:
Keywords:
Cardiomyocyte, cardiovascular disease, diabetis, H9c2 cells, palmitate, prolylcarboxypeptidase.
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.
Method: 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-κB 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.
Conclusion: 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.
