Altered Prolylcarboxypeptidase Expression and Function in Response to Different Risk Factors of Diabetes

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.

Cite this article as:

Tabrizian Tahmineh, Floyd Lillie and Shariat-Madar Zia, Altered Prolylcarboxypeptidase Expression and Function in Response to Different Risk Factors of Diabetes, Cardiovascular & Hematological Agents in Medicinal Chemistry 2016; 14 (3) . https://dx.doi.org/10.2174/1871525714666161229130508

DOI https://dx.doi.org/10.2174/1871525714666161229130508	Print ISSN 1871-5257
Publisher Name Bentham Science Publisher	Online ISSN 1875-6182