Erythropoietin activates SIRT1 to protect human cardiomyocytes against doxorubicin-induced mitochondrial dysfunction and toxicity

Cui, Lan; Guo, Jiabin; Zhang, Qiang; Yin, Jian; Li, Jin; Zhou, Wei; Zhang, Tingfen; Yuan, Haitao; Zhao, Jun; Zhang, Li; Carmichael, Paul L.; Peng, Shuangqing

doi:10.1016/j.toxlet.2017.04.018

Cited by 70 publications

(65 citation statements)

References 60 publications

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“…transition. An increased mitochondrial DNA copy number and a restored MMP have been reported to reflect mitochondrial homeostasis (Cui et al, 2017b(Cui et al, , 2017a homeostasis attenuates phenotypic transition of VSMCs to an osteogenic phenotype, an important pathological process in VC (Ma et al, 2018). During our study, the promotion of MMP in the presence of miR-30b mimic in VSMCs indicated that miRNA-30b could regulate VC via maintaining mitochondrial homeostasis.…”

Section: Discussionsupporting

confidence: 54%

Restoration of microRNA‐30b expression alleviates vascular calcification through the mTOR signaling pathway and autophagy

Qiu

Sheng

et al. 2019

Journal Cellular Physiology

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Pathological calcification represents an event that consequently leads to a distinct elevation in the morbidity and mortality of patients with chronic kidney disease (CKD) in addition to strengthening its correlation with hyperphosphatemia. Epigenomic regulation by specific microRNAs (miRNAs) is reported to be involved in ectopic calcification. However, the finer molecular mechanisms governing this event remain unclear. Hence, this study aimed to identify the potential miRNAs involved in vascular calcification (VC) development and progression. Initially, mitochondrial membrane potential (MMP), autophagy‐specific markers (LC3II/LC3I and Beclin1) and phenotype‐specific markers of osteoblasts (runt‐related transcription factor 2 and Msx2) were measured to evaluate autophagy and VC in β‐glycerophosphate‐induced vascular smooth muscle cells (VSMCs) with either miR‐30b restoration or miR‐30b knockdown performed in vitro. The VC in vivo was represented by calcified nodule formation in the aorta of the rats undergoing 5/6 nephrectomy followed by a 1.2% phosphorus diet using Alizarin Red staining. SOX9 was verified as the target of miR‐30b according to luciferase activity determination. Restoration of miR‐30b was revealed to markedly diminish the expression of SOX9 while acting to inhibit activation of the mTOR signaling pathway. Knockdown of miR‐30b reduced MMP and autophagy, elevated VC, and suppressed the presence of rapamycin (an inhibitor of the mTOR signaling pathway). In addition, upregulated expression of miR‐30b attenuated VC in vivo. Taken together, the key findings of this study identified the inhibitory role of miR‐30b in VC, presenting an enhanced understanding of miRNA as a therapeutic target to curtail progressive VC in hyperphosphatemia of CKD.

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Section: Discussionsupporting

confidence: 54%

Restoration of microRNA‐30b expression alleviates vascular calcification through the mTOR signaling pathway and autophagy

Qiu

Sheng

et al. 2019

Journal Cellular Physiology

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“…Mitochondria are cellular structures that make ATP, which help power cells. Mitochondria regulate apoptosis, autophagy, and intracellular signaling in cardiomyocytes (Cui et al, ; Liesa & Shirihai, ; Saito & Sadoshima, ). In this study, Lin28a overexpression and Mst1 knockdown alleviated HG‐induced mitochondrial ultrastructure impairment, and increased the ATP content, CS activity, and the activities of complexes I/II/III/IV/V.…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 92%

Lin28a protects against diabetic cardiomyopathy through Mst1 inhibition

You

Cheng

et al. 2019

Journal Cellular Physiology

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Lin28a has been found to enhance glucose uptake and insulin sensitivity. Lin28a alleviates cardiac dysfunction under various pathological conditions. However, the effects and underlying mechanisms of Lin28a on diabetic cardiomyopathy (DCM) are not well-understood. The aim of this study was to determine whether Lin28a protects against DCM and the potential mechanisms. Two to three days old mouse neonatal primary cardiomyocytes were randomized for treatment with adenoviruses harboring Lin28a and mammalian sterile 20-like kinase 1 (Mst1) short hairpin RNA, 48 hr before culturing in normal or high glucose medium. Cardiomyocyte apoptosis, autophagy, mitochondrial morphology, adenosine triphosphate content, and cytokine levels in the high glucose or normal conditions were observed between all groups. Either Lin28a overexpression or Mst1 knockdown alleviated mitochondrial ultrastructure impairment, decreased cytokine levels, inhibited apoptosis, and enhanced autophagy in primary neonatal mouse cardiomyocytes treated with high glucose. Importantly, the protective effects of Lin28a and Mst1 disappeared after treatment with 3-methyladenine, an autophagy inhibitor. Interestingly, in Mst1 knockdown cardiomyocytes, Lin28a overexpression failed to further enhance autophagy and alleviate high glucose-induced cardiomyocyte injury, which implies the protective roles of Lin28a counteracting high glucose-induced cardiomyocyte injury are dependent on Mst1 inhibition. Furthermore, co-immunoprecipitation and immunofluorescence double staining suggested that there were no direct interactions between Mst1 and Lin28a. Lin28a increased the expression of Akt, which inhibited the activation of Mst1-mediated apoptotic pathways. K E Y W O R D S apoptosis, autophagy, diabetic cardiomyopathy, Lin28a, Mst1 SUPPORTING INFORMATION Additional supporting information may be found online in the Supporting Information section. How to cite this article: You P, Cheng Z, He X, et al. Lin28a protects against diabetic cardiomyopathy through Mst1 inhibition. J Cell Physiol. 2020;235:4455-4465.

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“…SIRT1 is involved in multiple disease processes that include cancer (106, 111-113), vascular disease (39, 114-117), altered cellular metabolism (12, 102, 103, 118, 119), diabetes (18, 120-123), and neurodegenerative disorders (106, 124, 125). Many of these processes require the modulation of autophagy by SIRT1 (12, 40, 126, 127).…”

Section: Circadian Rhythm Mtor and Sirt1mentioning

confidence: 99%

Moving to the Rhythm with Clock (Circadian) Genes, Autophagy, mTOR, and SIRT1 in Degenerative Disease and Cancer

Maiese¹

2017

CNR

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Background The mammalian circadian clock and its associated clock genes are increasingly be recognized as critical components for a number of physiological and disease processes that extend beyond hormone release, thermal regulation, and sleep-wake cycles. New evidence suggests that clinical behavior disruptions that involve prolonged shift work and even space travel may negatively impact circadian rhythm and lead to multi-system disease. Methods In light of the significant role circadian rhythm can hold over the body's normal physiology as well as disease processes, we examined and discussed the impact circadian rhythm and clock genes hold over lifespan, neurodegenerative disorders, and tumorigenesis. Results In experimental models, lifespan is significantly reduced with the introduction of arrhythmic mutants and leads to an increase in oxidative stress exposure. Interestingly, patients with Alzheimer's disease and Parkinson's disease may suffer disease onset or progression as a result of alterations in the DNA methylation of clock genes as well as prolonged pharmacological treatment for these disorders that may lead to impairment of circadian rhythm function. Tumorigenesis also can occur with the loss of a maintained circadian rhythm and lead to an increased risk for nasopharyngeal carcinoma, breast cancer, and metastatic colorectal cancer. Interestingly, the circadian clock system relies upon the regulation of the critical pathways of autophagy, the mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), and silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1) as well as proliferative mechanisms that involve the wingless pathway of Wnt/β-catenin pathway to foster cell survival during injury and block tumor cell growth. Conclusions Future targeting of the pathways of autophagy, mTOR, SIRT1, and Wnt that control mammalian circadian rhythm may hold the key for the development of novel and effective therapies against aging- related disorders, neurodegenerative disease, and tumorigenesis.

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Erythropoietin activates SIRT1 to protect human cardiomyocytes against doxorubicin-induced mitochondrial dysfunction and toxicity

Cited by 70 publications

References 60 publications

Restoration of microRNA‐30b expression alleviates vascular calcification through the mTOR signaling pathway and autophagy

Restoration of microRNA‐30b expression alleviates vascular calcification through the mTOR signaling pathway and autophagy

Lin28a protects against diabetic cardiomyopathy through Mst1 inhibition

Moving to the Rhythm with Clock (Circadian) Genes, Autophagy, mTOR, and SIRT1 in Degenerative Disease and Cancer

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