miR-499 protects cardiomyocytes from H2O2-induced apoptosis via its effects onPdcd4andPacs2

Wang, Jiaji; Jia, Zhonghua; Zhang, Chenguang; Sun, Min; Wang, Weiping; Chen, Ping; Ma, Kangtao; Zhang, Youyi; Li, Xianhui; Zhou, Chen

doi:10.4161/rna.28300

Cited by 105 publications

(64 citation statements)

References 43 publications

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“…Additionally, miR-499 also exerts an anti-apoptotic effect on cardiac cells induced by H 2 O 2 . Lower levels of miR-499 in the myocardium are associated with decreased cardiac systolic function during reperfusion as compared with levels of other miRNAs [20]. Furthermore, miR-499 levels in the myocardium are negatively correlated with levels of cardiac troponin complex in the peripheral blood, indicating that myocardial levels of miR-499 might reflect the degree of cardiomyocyte damage [19].…”

Section: Discussionmentioning

confidence: 99%

“…miR-499 also protects the myocardium against myocardial I/R injury with cardiopulmonary bypass, suggesting that mir-499 may be a potential therapeutic target in cardiac protection during open-heart surgery [19]. Wang et al also demonstrated that miR-499 inhibits the mitochondrial apoptosis pathway and protects cardiomyocytes against H 2 O 2 -induced injury [20]. PDCD4 is an important target gene that protects cardiomyocytes from apoptosis induced by ischemia during ischemic preconditioning [21].…”

Section: Introductionmentioning

confidence: 99%

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Ischemic Postconditioning-Regulated miR-499 Protects the Rat Heart Against Ischemia/Reperfusion Injury by Inhibiting Apoptosis through PDCD4

Zhu

Yao

Wang

et al. 2016

Cell Physiol Biochem

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Background: Here, we determined miR-499 involvement in the protective effect of ischemic postconditioning (IPC) against myocardial ischemia/reperfusion (I/R) injury and identified the underlying mechanisms. Methods: To investigate the cardioprotective effect of IPC-induced miR-499, rats were divided into the following five groups: sham, I/R, IPC, IPC + scramble, and IPC + antagomiR-499. Hemodynamic indexes were measured by carotid-artery intubation to assess left ventricular function . Ischemia and infarction areas of rat hearts were determined by Evans blue and triphenyltetrazolium chloride staining, and cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end-labeling assay. Results: IPC attenuated I/R-induced infarct size of the left ventricle (45.28 ± 5.40% vs. 23.56 ± 6.20%, P < 0.05), myocardial apoptosis, and decreased creatine kinase (1867.31 ± 242.41% vs. 990.21 ± 172.39%, P < 0.05), lactate dehydrogenase (2257.50 ± 305.11% vs. 1289.11 ± 347.28%, P < 0.05), and malondialdehyde levels (7.18 ± 1.63% vs. 4.85 ± 1.52%, P < 0.05). Additionally, left ventricular systolic pressure, +dp/dtmax, and -dp/dtmax were elevated, and left ventricular end diastolic pressure was significantly reduced in the IPC group. Furthermore, IPC-mediated cardiac protection against I/R injury was inhibited in vivo and in vitro by knockdown of cardiac miR-499, suggesting that miR-499 may participate in the protective function of IPC against I/R injury through targeting programmed cell death 4 (PDCD4). Conclusion: Our data revealed that IPC-regulated miR-499 plays an important role in IPC-mediated cardiac protection against I/R injury by targeting PDCD4.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ischemic Postconditioning-Regulated miR-499 Protects the Rat Heart Against Ischemia/Reperfusion Injury by Inhibiting Apoptosis through PDCD4

Zhu

Yao

Wang

et al. 2016

Cell Physiol Biochem

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“…In hepatocellular carcinoma cells, inhibitors of apoptosis (IAPs) target PACS-2 for proteasomal degradation, thereby protecting the cancer cells from being killed by TRAIL (Guicciardi et al, 2014). In cardiomyocytes, miR499 prevents Bid-dependent apoptosis by downregulating PACS-2 (Wang et al, 2014). Not surprisingly, herpesviruses also exploit the ability of PACS-2 to traffic proteins to mitochondria.…”

Section: Introductionmentioning

confidence: 99%

Caught in the act – protein adaptation and the expanding roles of the PACS proteins in tissue homeostasis and disease

Thomas

Aslan

Thomas

et al. 2017

Journal of Cell Science

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Vertebrate proteins that fulfill multiple and seemingly disparate functions are increasingly recognized as vital solutions to maintaining homeostasis in the face of the complex cell and tissue physiology of higher metazoans. However, the molecular adaptations that underpin this increased functionality remain elusive. In this Commentary, we review the PACS proteins -which first appeared in lower metazoans as protein traffic modulators and evolved in vertebrates to integrate cytoplasmic protein traffic and interorganellar communication with nuclear gene expression -as examples of protein adaptation 'caught in the act'. Vertebrate PACS-1 and PACS-2 increased their functional density and roles as metabolic switches by acquiring phosphorylation sites and nuclear trafficking signals within disordered regions of the proteins. These findings illustrate one mechanism by which vertebrates accommodate their complex cell physiology with a limited set of proteins. We will also highlight how pathogenic viruses exploit the PACS sorting pathways as well as recent studies on PACS genes with mutations or altered expression that result in diverse diseases. These discoveries suggest that investigation of the evolving PACS protein family provides a rich opportunity for insight into vertebrate cell and organ homeostasis.

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“…miR-499 was found to be expressed in the heart, and circulating miR-499 is suggested to be a sensitive biomarker for acute myocardial infarction [19]. It was also found to protect cardiomyocytes from H 2 O 2 -induced apoptosis by targeting Pdcd4 and Pacs2 [20]. However, no study has explored the role of miR-499 in hepatic insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

MiR-499-5p Contributes to Hepatic Insulin Resistance by Suppressing PTEN

Wang

Zhang

Pan

et al. 2015

Cell Physiol Biochem

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Background: Type 2 diabetes afflicts 95% of diabetes patients. Recent data suggest that miRNAs play a key role in insulin production, secretion and function. This study aims to explore the specific role of miR-499-5p in hepatic insulin resistance. Methods: The miRNA expression levels in the livers of db/db mice were analyzed using miRNA chips and were verified by real-time PCR. miR-499-5p mimics and an inhibitor were transfected into NCTC1469 cells. Then, the PI3K/AKT signaling pathway and glycogen level were determined. The target genes of miR-499-5p were predicted by bioinformatics and then confirmed by dual luciferase reporter assay and Western blot. To establish an insulin resistance (IR) animal model, C57BL/6 mice were fed a high-fat diet (HFD). The level of miR-499-5p in the livers of HFD-fed mice was upregulated through tail vein injection of adenovirus vectors (ad) containing miR-499-5p mimics. The glucose tolerance test (GTT) and insulin tolerance test (ITT) were used to determine glucose tolerance and insulin tolerance, respectively. Results: MicroRNA chips and qPCR showed that miR-499-5p was significantly decreased in the livers of db/db mice. Downregulation of miR-499-5p impaired the insulin signaling pathway and glycogen synthesis, whereas upregulation of miR-499-5p promoted the insulin signaling pathway and glycogen synthesis in NCTC1469 cells. The dual luciferase reporter assay and Western blot demonstrated that PTEN was the target gene of miR-499-5p. Compared with the control group, miR-499-5p was increased 2.1-fold in the livers of HFD-fed mice. By tail vein injection of adenovirus vector containing miR-499-5p mimics, GTT and ITT were improved in HFD-fed mice. Conclusion: Downregulation of the miR-499-5p level impaired the PI3K/AKT/GSK signaling pathway and glycogen synthesis by targeting PTEN.

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miR-499 protects cardiomyocytes from H₂O₂-induced apoptosis via its effects onPdcd4andPacs2

Cited by 105 publications

References 43 publications

Ischemic Postconditioning-Regulated miR-499 Protects the Rat Heart Against Ischemia/Reperfusion Injury by Inhibiting Apoptosis through PDCD4

Ischemic Postconditioning-Regulated miR-499 Protects the Rat Heart Against Ischemia/Reperfusion Injury by Inhibiting Apoptosis through PDCD4

Caught in the act – protein adaptation and the expanding roles of the PACS proteins in tissue homeostasis and disease

MiR-499-5p Contributes to Hepatic Insulin Resistance by Suppressing PTEN

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