PTEN induced putative kinase 1 (PINK1) alleviates angiotensin II-induced cardiac injury by ameliorating mitochondrial dysfunction

Xiong, Wenjun; Hua, Jinghai; Liu, Zuheng; Cai, Wanqiang; Bai, Yujia; Zhan, Qimin; Lai, Wenyan; Zeng, Qingchun; Ren, Hao; Xu, Dingli

doi:10.1016/j.ijcard.2018.03.054

Cited by 39 publications

(31 citation statements)

References 41 publications

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“…Negative: uninfected cells; S100P shRNA: cells infected with S100P interference lentiviruses; S100P overexpression: cells infected with S100P overexpression lentiviruses; Control: Cells infected with scrambled sequence lentiviruses (A, B, C, D) or empty vector (E, F) localized expression of S100P and EZRIN in endometrial cancer cells, which indicated that S100P might interact with Ezrin during the occurrence and progress of endometrial cancer. Interestingly, increased levels of Ezrin have also been reported in atypical endometrial hyperplasia and uterine endometrioid adenocarcinoma [28][29][30]. These reports further supported our hypothesis.…”

Section: Discussionsupporting

confidence: 89%

Promotion of the occurrence of endometrioid carcinoma by S100 calcium binding protein P

et al. 2020

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Background: Endometrial cancer, one of the most common malignant tumors, is a serious threat to women's health. Endometrial hyperplasia is a precursor of endometrial cancer. S100 calcium binding protein P (S100P) has been found to play important roles in many types of cancer. The present study aimed to investigate the expression of S100P in endometrial cancer and its precursor lesions, and to explore the possible mechanisms. Methods: We collected paraffin sections of normal endometrium, simple and complex non-atypical hyperplasia, atypical hyperplasia, and endometrioid carcinoma. The expression of S100P in endometrial cancer and its precancerous lesions was observed using immunohistochemistry. We also cultured primary endometrial cells and endometrial cancer cell lines (Ishikawa and RL95-2), and observed the expression of S100P in these cells. Laser confocal microscopy was used to observe the co-localization of S100P and its interacting protein Ezrin in RL95-2 cells. We employed lentiviruses to knockdown and overexpress S100P and then detected the F-actin distribution and cell invasion using phalloidin staining and Transwell assays. Results: There was a gradual increase in the S100P signal as the disease progressed from normal endometrium and simple non-atypical hyperplasia, to complex non-atypical hyperplasia, atypical hyperplasia, and then to endometrial cancer. S100P was mainly distributed in the cytoplasm and co-localized with Ezrin in endometrial cancer cells. After knocking down S100P, F-actin aggregated in the nucleus or to the local cell membrane. Furthermore, knockdown of S100P in Ishikawa cells decreased their cell invasion capability. Meanwhile, S100P overexpression in endometrial stromal cells increased cell invasion. Conclusions: These data suggested that S100P might be involved in the occurrence and development of endometrial cancer via interaction with Ezrin and reorganization of F-actin to promote cell invasion.

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Section: Discussionsupporting

confidence: 89%

Promotion of the occurrence of endometrioid carcinoma by S100 calcium binding protein P

et al. 2020

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“…Neonatal rat cardiomyocytes were prepared from the hearts of 1- to 3-day-old Sprague-Dawley rats using enzymatic dissociation and cultured as previously described (Xiong et al, 2018). Recombinant adenoviruses for MFN2 overexpression (Ad-MFN2) were designed and synthesized by GeneChem Co., Ltd. (Shanghai, China).…”

Section: Methodsmentioning

confidence: 99%

Mitofusin 2 Participates in Mitophagy and Mitochondrial Fusion Against Angiotensin II-Induced Cardiomyocyte Injury

Xiong

et al. 2019

Front. Physiol.

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Background Mitochondrial dynamics play a critical role in mitochondrial function. The mitofusin 2 (MFN2) gene encodes a mitochondrial membrane protein that participates in mitochondrial fusion to maintain and operate the mitochondrial network. Moreover, MFN2 is essential for mitophagy. In Ang II-induced cardiac remodeling, the combined effects of MFN2-mediated mitochondrial fusion and mitophagy are unclear. This study was designed to explore a novel strategy for preventing cardiomyocyte injury via modulation of mitochondrial dynamics. Methods We studied the function of MFN2 in mitochondrial fusion and mitophagy in Ang II-stimulated cardiomyocyte injury. Cardiomyocyte injury experiments, including reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), and apoptosis rate of cardiomyocytes were performed. The mitochondrial morphology in cardiomyocytes was examined via transmission electron microscopy (TEM) and confocal microscopy. Autophagic levels in response to Ang II were examined by immunoblotting of autophagy-related proteins. Moreover, PINK1/MFN2/Parkin pathway-related proteins were examined. Results With stimulation by Ang II, MFN2 expression was progressively reduced. MFN2 deficiency impaired mitochondrial quality, resulting in exacerbated mitochondrial damage induced by Ang II. The Ang II-induced increases in ROS production and apoptosis rate were alleviated by MFN2 overexpression. Moreover, MFN2 alleviated the Ang II-induced reduction in MMP. MFN2 promoted mitochondrial fusion, and MFN2 promoted Parkin translocation and phosphorylation, leading to mitochondrial autophagy. The effects of MFN2 overexpression were reversed by autophagy inhibitors. Conclusion Mitofusin 2 promotes Parkin translocation and phosphorylation, leading to mitophagy to clear damaged mitochondria. However, the beneficial effects of MFN2 were reversed by autophagy inhibitors. Additionally, MFN2 participates in mitochondrial fusion to maintain mitochondrial quality. Thus, MFN2 participated in mitophagy and mitochondrial fusion against Ang II-induced cardiomyocyte injury.

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“…However, mitochondria are not only major sites of energy metabolism, but also regulate cell apoptosis in the high energy-consuming organ [22]. There is growing evidence that indicates that mitochondria dysfunction is closely related to cardiomyocyte apoptosis induced by I/R injury [23,24].With stimulation to mitochondria of ROS may lead to apoptosis. Mitochondria-related apoptotic pathways can be activated after the release of pro-apoptotic proteins.…”

Section: Discussionmentioning

confidence: 99%

Reduced β2-glycoproteinI Alleviated Rat Myocardial Ischemia/Reperfusion Injury via Mitochondrial Protection and Inhibition of Apoptosis

Zhou¹,

Meng²,

Xiao³

et al. 2020

Preprint

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BackgroundMyocardial ischemia/reperfusion (I/R) injury is one of the most important reasons for death of coronary heart disease after vascular recanalization. New evidences have shown that β2-glycoprotein I (β2GPI) plays a protective role in cardiovascular diseases. This study aims to evaluate the effects of reduced β2GPI (R-β2GPI), one form of β2GPI, on myocardial I/R injury, and to explore related mechanisms. MethodsThe in vivo myocardial I/R models of Sprague Dawley rats and in vitro hypoxia/reoxygenation(H/R) models of H9c2 cells were established. The myocardial infarction and morphological changes in SD rats were measured by the TTC staining and HE staining. Creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) levels in plasma were detected by ELISA Assay kit. Terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) method and caspase-3 colorimetric assay kit were used to determine myocardial apoptosis. Intracellular reactive oxygen species (ROS) generation and mitochondrial membrane potential of H9c2 cells were measured by fluorescent probe DCFH-DA and JC-1 fluorescent staining respectively. To evaluate cell damage, cell viability was assessed by determining the release of lactate dehydrogenase (LDH). The ratio of Bcl-2/Bax at mRNA level was detected by reverse transcription-polymerase chain reaction (RT-PCR). Western blot analysis was used to detect the expression levels of total Akt and phosphorylated Akt as well as the expression levels of total GSK-3βand phosphorylated GSK-3β in H9c2 cells. ResultsOur results suggested that R-β2GPI improved I/R model rats’ heart function, decreased infarct size, reduced serum CK-MB, cTnI levels, cell apoptosis and caspase3 activity. In vitro, R-β2GPI decreased LDH leakage, reduced ROS generation, maintained mitochondrial membrane potential and increased bcl-2/bax mRNA ratio; increased phosphorylation of Akt and GSK-3β in H9c2 cells following Hypoxia/Reoxygenation (H/R) jnjury. ConclusionR-β2GPI alleviated myocardial I/R (or H/R) injury by reducing oxidative stress and inhibiting mitochondrial apoptotic pathway via increasing the phosphorylation of Akt/GSK-3β.

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PTEN induced putative kinase 1 (PINK1) alleviates angiotensin II-induced cardiac injury by ameliorating mitochondrial dysfunction

Cited by 39 publications

References 41 publications

Promotion of the occurrence of endometrioid carcinoma by S100 calcium binding protein P

Promotion of the occurrence of endometrioid carcinoma by S100 calcium binding protein P

Mitofusin 2 Participates in Mitophagy and Mitochondrial Fusion Against Angiotensin II-Induced Cardiomyocyte Injury

Reduced β2-glycoproteinI Alleviated Rat Myocardial Ischemia/Reperfusion Injury via Mitochondrial Protection and Inhibition of Apoptosis

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