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

Author(s): Tahmineh Tabrizian, Lillie Floyd, Zia Shariat-Madar

Journal Name: Cardiovascular & Hematological Agents in Medicinal Chemistry
Formerly Current Medicinal Chemistry - Cardiovascular & Hematological Agents

Volume 14 , Issue 3 , 2016

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Background: Prolylcarboxypeptidase (PRCP, EC: 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.

Keywords: Cardiomyocyte, cardiovascular disease, diabetis, H9c2 cells, palmitate, prolylcarboxypeptidase.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2016
Published on: 29 December, 2016
Page: [175 - 189]
Pages: 15
DOI: 10.2174/1871525714666161229130508
Price: $65

Article Metrics

PDF: 34
PRC: 1