Salidroside attenuates endothelial cellular senescence via decreasing the expression of inflammatory cytokines and increasing the expression of SIRT3

Xing, Shasha; Li, Jian; Chen, Lin; Yang, Yanwen; He, Pinglin; Li, Jun; Yang, Jin

doi:10.1016/j.mad.2017.12.005

Cited by 45 publications

(24 citation statements)

References 33 publications

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“…Accumulating evidence has shown that ROS are the major initiators of myocardial damage in myocardial I/R injury and the attenuation of oxidative stress in myocardial cell has been demonstrated to improve myocardial function following ischemia (4,33). It has been demonstrated that salidroside may suppress oxidative stress-induced endothelial dysfunction, cardiomyocyte injury and necrosis, and cerebral ischemia/reperfusion injury, through decreasing excessive ROS generation and improving mitochondrial function (34)(35)(36)(37). However, the effect of salidroside in myocardial I/R injury-induced oxidative stress has not been studied.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑21 mediates the protective effects of salidroside against hypoxia/reoxygenation‑induced myocardial oxidative stress and inflammatory response

Liu

Wei²,

Lan

et al. 2020

Exp Ther Med

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Myocardial ischemia-reperfusion (I/R) injury is the oxidative stress and inflammatory response that occurs when a tissue is reperfused following a prolonged period of ischemic injury. Growing evidence has demonstrated that microRNAs (miRs) are essential in the development of myocardial I/R injury. Salidroside, a phenylpropanoid glycoside isolated from a traditional Chinese medicinal plant, Rhodiola rosea, possesses multiple pharmacological functions and protects against myocardial I/R injury in vitro and in vivo. However, the role of miRs in the cardioprotective effects of salidroside against myocardial I/R injury has not been studied, to the best of our knowledge. In the present study, the role of miR21 in the underlying mechanism of salidroside-induced protection against oxidative stress and inflammatory injuries in hypoxia/reoxygenation (H/R)-treated H9c2 cardiomyocytes was determined. The cell viability was assessed with an MTT assay. Lactate dehydrogenase (LDH) release, caspase-3 activity, malondialdehyde (MDA) level, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were determined by commercial kits. Cell apoptosis was measured by flow cytometry. Intracellular reactive oxygen species (ROS) generation was monitored by DCFH-DA. The miR-21 level was quantified by reverse transcription-quantitative (RT-q)PCR. The interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α levels were measured by RT-qPCR and ELISA. The results showed that salidroside pretreatment significantly increased cell viability and decreased the release of LDH, accompanied by an increase in miR-21 expression in H/R-treated H9c2 cells and a miR-21 inhibitor reversed these effects. In addition, the miR-21 inhibitor also abrogated the inhibition of salidroside on H/R-induced increases in apoptosis and caspase-3 activity in H9c2 cells. Salidroside mitigated H/R-induced oxidative stress as illustrated by the downregulation of ROS generation and MDA level and increased the activities of the antioxidant enzymes, SOD and GSH-Px, all of which were abrogated in cells transfected with the miR-21 inhibitor. Salidroside induced a decrease in the expression and levels of the pro-inflammatory cytokines, IL-6, IL-1β and TNF-α, which were prevented by the miR-21 inhibitor. Together, these results provide evidence of the beneficial effects of salidroside against myocardial I/R injury by reducing myocardial oxidative stress and inflammation which are enhanced by increasing miR-21 expression.

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Section: Discussionmentioning

confidence: 99%

MicroRNA‑21 mediates the protective effects of salidroside against hypoxia/reoxygenation‑induced myocardial oxidative stress and inflammatory response

Liu

Wei²,

Lan

et al. 2020

Exp Ther Med

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“…LPS upregulates Ang-2, leading to vascular leakage, while SIRT3 inhibits the expression of Ang-2 to maintain vascular integrity 170 . Up-regulation of SIRT3 can attenuate endothelial cellular senescence to decrease the risk of atherosclerosis 171 . In addition, activation of SIRT3 can suppress osteoarthritis by maintaining mitochondrial metabolism stability 172 .…”

Section: Sirt3 and Human Diseasementioning

confidence: 99%

Mitochondrial Sirtuin 3: New emerging biological function and therapeutic target

Zhang¹,

Xiang²,

Liu³

et al. 2020

Theranostics

271

238

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Sirtuin 3 (SIRT3) is one of the most prominent deacetylases that can regulate acetylation levels in mitochondria, which are essential for eukaryotic life and inextricably linked to the metabolism of multiple organs. Hitherto, SIRT3 has been substantiated to be involved in almost all aspects of mitochondrial metabolism and homeostasis, protecting mitochondria from a variety of damage. Accumulating evidence has recently documented that SIRT3 is associated with many types of human diseases, including age-related diseases, cancer, heart disease and metabolic diseases, indicating that SIRT3 can be a potential therapeutic target. Here we focus on summarizing the intricate mechanisms of SIRT3 in human diseases, and recent notable advances in the field of small-molecule activators or inhibitors targeting SIRT3 as well as their potential therapeutic applications for future drug discovery.

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“…Similarly to the other members of the sirtuin family, depletion of SIRT3 has been shown to reduce human lifespan (Bellizzi et al, 2005;Brown et al, 2013). Notably, strategies aimed to upregulate SIRT3 in endothelial cells resulted in a higher protection against stress-induced premature senescence, an effect mediated by the deacetylation of FoxO3 (Liu et al, 2015;Xing et al, 2018). For some aspects, ECs seem to escape the rules describing the senescence-associated metabolic shift that have been postulated from studies in other cell lineages.…”

Section: Metabolic Features Of Endothelial Cellsmentioning

confidence: 99%

Where Metabolism Meets Senescence: Focus on Endothelial Cells

et al. 2019

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Despite the decline in their proliferative potential, senescent cells display a high metabolic activity. Senescent cells have been shown to acquire a more glycolytic state even in presence of high oxygen levels, in a way similar to cancer cells. The diversion of pyruvate, the final product of glycolysis, away from oxidative phosphorylation results in an altered bioenergetic state and may occur as a response to the enhanced oxidative stress caused by the accumulation of dysfunctional mitochondria. This metabolic shift leads to increased AMP/ATP and ADP/ATP ratios, to the subsequent AMPK activation, and ultimately to p53-mediated growth arrest. Mounting evidences suggest that metabolic reprogramming is critical to direct considerable amounts of energy toward specific activities related to the senescent state, including the senescence-associated secretory phenotype (SASP) and the modulation of immune responses within senescent cell tissue microenvironment. Interestingly, despite the relative abundance of oxygen in the vascular compartment, healthy endothelial cells (ECs) produce most of their ATP content from the anaerobic conversion of glucose to lactate. Their high glycolytic rate further increases during senescence. Alterations in EC metabolism have been identified in age-related diseases (ARDs) associated with a dysfunctional vasculature, including atherosclerosis, type 2 diabetes and cardiovascular diseases. In particular, higher production of reactive oxygen species deriving from a variety of enzymatic sources, including uncoupled endothelial nitric oxide synthase and the electron transport chain, causes DNA damage and activates the NAD +-consuming enzymes polyADP-ribose polymerase 1 (PARP1). These non-physiological mechanisms drive the impairment of the glycolytic flux and the diversion of glycolytic intermediates into many pathological pathways. Of note, accumulation of senescent ECs has been reported in the context of ARDs. Through their pro-oxidant, pro-inflammatory, vasoconstrictor, and prothrombotic activities, they negatively impact on vascular physiology, promoting both the onset and development of ARDs. Here, we review the current knowledge on the cellular senescence-related metabolic changes and their contribution to the mechanisms underlying the pathogenesis of ARDs, with a particular focus on ECs. Moreover, current and potential interventions aimed at modulating EC metabolism, in order to prevent or delay ARD onset, will be discussed.

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Salidroside attenuates endothelial cellular senescence via decreasing the expression of inflammatory cytokines and increasing the expression of SIRT3

Cited by 45 publications

References 33 publications

MicroRNA‑21 mediates the protective effects of salidroside against hypoxia/reoxygenation‑induced myocardial oxidative stress and inflammatory response

MicroRNA‑21 mediates the protective effects of salidroside against hypoxia/reoxygenation‑induced myocardial oxidative stress and inflammatory response

Mitochondrial Sirtuin 3: New emerging biological function and therapeutic target

Where Metabolism Meets Senescence: Focus on Endothelial Cells

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