E3 Ubiquitin Ligase Parkin-Mediated Mitophagy in Cardiomyocyte Injury at Tumor-Bearing State
10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.2022.0203
- VernacularTitle:E3泛素-蛋白连接酶Parkin介导线粒体自噬参与荷瘤小鼠心肌损伤
- Author:
Shi-jie DENG
1
;
Xing-hui LI
1
;
Wei-bin CAI
1
Author Information
1. Guangdong Provincial Engineering and Technology Research Center for Disease-Model Animals//Laboratory Animal Center， Sun Yat-sen University， Guangzhou 510006， China
- Publication Type:Journal Article
- Keywords:
Parkin;
tumor-bearing state;
cardiomyocyte injury;
mitophagy
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2022;43(2):181-191
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo observe the myocardial injury in tumor-bearing mice， and to explore the role and mechanism of park2 gene-encoded E3 ubiquitin protein ligase Parkin-mediated mitophagy in myocardial injury of tumor-bearing mice. MethodsPCR and Western Blot were used to verify park2-/- mice， the tumor-bearing animal models were constructed by subcutaneous transplantation， small animal ultrasound imaging system was used to monitor cardiac structure and function， the changes in left ventricular internal dimensions （LVD）， left ventricular volume （LVV） ， ejection fraction （EF）， fractional shortening （FS）， and left ventricular wall thickness （LVW） were measured. Morphological changes of hearts were analyzed by pathological techniques. Fluo-3， Rhod-2， DHE-ROS and JC-1 probes were used for the detection of mitochondrial damage indicators. qPCR technology was used to evaluate mitochondriogenesis related factors tfam and nrf1， mitochondrial fusion related factors opa1 and mfn2， mitochondrial fission related factor fis1， and mitophagy related gene park2. Expression of LC3 Ⅱ， LC3 Ⅰ and Parkin was assessed by Western Blot. ResultsThe small animal ultrasound imaging revealed that B16 melanoma-bearing mice had a significant reduction in cardiac function（P<0.01）. Transmission electron microscopy （TEM） showed increased numbers of mitochondria and mitochondria vacuolization in tumor-bearing mice（P=0.023）. Further molecular analysis indicated that tumor-bearing state could cause mitochondrial damage in cardiomyocytes and activate mitophagy. There was significantly increased mortality in tumor-bearing park2-/- mice （P<0.05）. Mitophagy was inhibited in park2-/- mice and more severe mitochondrial damage was noted （P<0.05）. ConclusionE3 ubiquitin protein ligase Parkin plays a protective role in cardiomyocyte injury at a tumor-bearing state， which is associated with E3 ubiquitin protein ligase Parkin-mediated mitophagy.
