Involvement of brain natriuretic peptide signaling pathway in the cardioprotective action of sitagliptin
| Autor: | Hanan S. El-Abhar, Hesham M. Mahmoud, Mona F. Schaalan, Samah S. Abbas |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Cardiotonic Agents Dipeptidyl Peptidase 4 Carbazoles 030204 cardiovascular system & hematology Pharmacology 03 medical and health sciences Cyclophilins 0302 clinical medicine Downregulation and upregulation Heart rate Natriuretic Peptide Brain medicine Animals Channel blocker Protein kinase A Cyclic GMP bcl-2-Associated X Protein chemistry.chemical_classification business.industry Caspase 3 Sitagliptin Phosphate Hemodynamics General Medicine Brain natriuretic peptide Rats 030104 developmental biology Enzyme chemistry Proto-Oncogene Proteins c-bcl-2 Sitagliptin Reperfusion Injury Signal transduction business Hydroxy Acids Decanoic Acids Cyclophilin D medicine.drug Signal Transduction |
| Zdroj: | Pharmacological reports : PR. 70(4) |
| ISSN: | 2299-5684 |
| Popis: | The current study is focusing on the role of brain natriuretic peptide (BNP), a substrate of dipeptidyl peptidase-4 (DPP-4) enzyme, and its signaling survival pathway in the cardioprotective mechanism of sitagliptin, a DPP-4 inhibitor. Male Wistar rats were randomized into 7 groups, sham, I/R, KT-5823 (selective protein kinase (PK) G inhibitor), 5-HD (selective mito-KATP channel blocker), sitagliptin (300 mg/kg, po), sitagliptin + KT-5823, and sitagliptin + 5-HD. Sitagliptin was administered for 3 days prior to induction of coronary I/R, while either KT-5823 or 5-HD was administered intravenously 5 min before coronary ligation. Pretreatment with sitagliptin provided significant protection against I/R injury as manifested by decreasing, percentage of infarct size, suppressing the elevated ST segment, reducing the increased cardiac enzymes, as well as DPP-4 activity and elevating both heart rate (HR) and left ventricular developed pressure (LVDP). However, the addition of either blocker to sitagliptin regimen reversed partly its cardioprotective effects. Although I/R increased BNP content, it unexpectedly decreased that of cGMP; nevertheless, sitagliptin elevated both parameters, an effect that was not affected by the use of the two blockers. On the molecular level, sitagliptin decreased caspase-3 activity and downregulated the mRNA levels of BNP, Bax, and Cyp D, while upregulated that of Bcl2. The use of either KT-5823 or 5-HD with sitagliptin hindered its effect on the molecular markers tested. The results of the present study suggest that the cardioprotective effect of sitagliptin is mediated partly, but not solely, through the BNP/cGMP/PKG survival signaling pathway. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink