Tissue kallikrein-related peptidase8 protects rat heart against acute ischemia reperfusion injury
| Autor: | Shiyu Ma, Jiankui Du, Meineng Huang, Jing Shang, Qing Yu, Yifei Wang, Guanxin Zhang, Xiaoyan Zhu, Binhai Cong, Ting Hu |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Cardiotonic Agents
Receptor Bradykinin B2 Ischemia Myocardial Reperfusion Injury 02 engineering and technology Pharmacology Bradykinin Biochemistry Rats Sprague-Dawley 03 medical and health sciences Structural Biology medicine Animals Receptor PAR-2 Myocytes Cardiac Extracellular Signal-Regulated MAP Kinases Molecular Biology Protein kinase B 030304 developmental biology 0303 health sciences TUNEL assay business.industry Myocardium Serine Endopeptidases Antagonist General Medicine Hypoxia (medical) 021001 nanoscience & nanotechnology medicine.disease Cyclic AMP-Dependent Protein Kinases Up-Regulation Apoptosis Phosphorylation Female medicine.symptom 0210 nano-technology business Reperfusion injury Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | International journal of biological macromolecules. 140 |
| ISSN: | 1879-0003 |
| Popis: | Tissue kallikrein-related peptidases (KLKs) play important roles in acute cardiac injury and cardiac remodeling. However, the exact cardiac actions of KLK8 have not been determined. Transgenic rat overexpressing KLK8 was established to examine the role of KLK8 in the heart. Cardiac injury was induced by ischemia/reperfusion (I/R) and examined by infarct size measurement and TUNEL staining. The molecular mechanisms were investigated in cultured neonatal rat cardiomyocytes (CMs). Western blot analysis was used to determine the protein levels. KLK8 protein level was significantly increased in the cardiac ischemic risk area. KLK8 overexpression mitigated I/R-induced cardiac injury, as evidenced by decreased infarct size and apoptosis in cardiac ischemic risk area in vivo. Via in vitro studies, it was found that KLK8 overexpression attenuated the Hypoxia/Reoxygenation (H/R) injury in CMs; both B2R and PAR2 antagonist significantly attenuated KLK8-induced protective actions under H/R injury. Moreover, KLK8 overexpressed CMs showed significant higher phosphorylation levels of Akt, ERK1/2 and PKA under H/R stimulation; B2R antagonist attenuated the phosphorylation levels of Akt and ERK1/2, while PAR2 antagonist attenuated the phosphorylation levels of PKA and ERK1/2. KLK8 protects the heart against I/R-induced cardiac injury, which may represent a new therapeutic target in cardiac medicine. |
| Databáze: | OpenAIRE |
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