Melatonin ameliorates excessive PINK1/Parkin-mediated mitophagy by enhancing SIRT1 expression in granulosa cells of PCOS

Yi, Shanling; Zheng, Bo; Zhu, Yujun; Cai, Yunni; Sun, Haixiang; Zhou, Jianjun

doi:10.1152/ajpendo.00006.2020

Cited by 95 publications

(52 citation statements)

References 40 publications

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“…However, melatonin effects were abolished by luzindole treatment. Previously, Sirt1 dependent Nrf2 expression has been reported, and after inhibition of Sirt1 via inhibitor, enhanced pro-inflammatory cytokines and as well as p-NF-κB expression were detected upon LPS administration, suggesting a sirt1 role in LPS induced neuroinflammation (Mendez-David et al, 2015;Santofimia-Castaño et al, 2015;Song et al, 2017;Shah et al, 2017;Ma et al, 2018;Wang et al, 2019;Merlo et al, 2020;Yi et al, 2020;Zhi W. et al, 2020).…”

Section: Discussionmentioning

confidence: 93%

Melatonin Act as an Antidepressant via Attenuation of Neuroinflammation by Targeting Sirt1/Nrf2/HO-1 Signaling

Ali

Hao

Ullah

et al. 2020

Front. Mol. Neurosci.

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Physical or psychological stress can cause an immunologic imbalance that disturbs the central nervous system followed by neuroinflammation. The association between inflammation and depression has been widely studied in recent years, though the molecular mechanism is still largely unknown. Thus, targeting the signaling pathways that link stress to neuroinflammation might be a useful strategy against depression. The current study investigated the protective effect of melatonin against lipopolysaccharide (LPS)-induced neuroinflammation and depression. Our results showed that LPS treatment significantly induced depressive-like behavior in mice. Moreover, LPStreatment enhanced oxidative stress, pro-inflammatory cytokines including TNFα, IL-6, and IL-1β, NF-κB phosphorylation, and glial cell activation markers including GFAP and Iba-1 in the brain of mice. Melatonin treatment significantly abolished the effect of LPS, as indicated by improved depressive-like behaviors, reduced cytokines level, reduced oxidative stress, and normalized LPS-altered Sirt1, Nrf2, and HO-1 expression. However, the melatonin protective effects were reduced after luzindole administration. Collectively, it is concluded that melatonin receptor-dependently protects against LPSinduced depressive-like behaviors via counteracting LPS-induced neuroinflammation.

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Section: Discussionmentioning

confidence: 93%

Melatonin Act as an Antidepressant via Attenuation of Neuroinflammation by Targeting Sirt1/Nrf2/HO-1 Signaling

Ali

Hao

Ullah

et al. 2020

Front. Mol. Neurosci.

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“…Our study explored, for the first time, the Mitophagy plays pivotal roles in the maintenance of mitochondrial homeostasis. Dysregulation of mitophagy has been found to be involved in the pathogenesis of a wide variety of diseases, such as Alzheimer's disease (Han et al, 2020), Rett syndrome (Cicaloni et al, 2020), polycystic ovary syndrome (Yi et al, 2020) and DN (Saxena et al, 2019). In HG-stimulated renal tubular cells, the mitochondrial dysfunction leads to excessive ROS release (Wei & Szeto, 2019 In the present study, we found a decreased level of miR-150-5p in response to HG, which exacerbated HG-mediated HK-2 cell injury by reducing mitophagy.…”

Section: Discussionmentioning

confidence: 99%

LncRNA NEAT1 accelerates renal tubular epithelial cell damage by modulating mitophagy via miR‐150‐5p–DRP1 axis in diabetic nephropathy

Yang

Zhou

Liu

et al. 2021

Experimental Physiology

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Diabetic nephropathy (DN) is a severe complication in diabetic patients, with a high mortality rate. Renal tubular injury is involved in the pathogenesis of DN. In this study, we aimed to uncover the regulatory roles of the NEAT1-miR-150-5p-DRP1 axis in an in vitro model of DN and its possible mechanisms. High glucose-challenged HK-2 cells were used as an in vitro DN model. NEAT1, miR-150-5p and DRP1 levels were assessed by RT-qPCR. Cell viability was determined by the MTT assay. MitoSOX Red and JC-1 were used to evaluate intracellular production of reactive oxygen species and mitochondrial membrane potential, respectively. Lactate dehydrogenase release and superoxide dismutase activity were assessed with commercial kits. The protein levels of DRP1, p62, BECN1(beclin 1) and BNIP3 were determined by western blotting. The interaction between NEAT1 (DRP1) and miR-150-5p was verified by a dual-luciferase reporter assay and an RNA immunoprecipitation assay. Our results showed that in response to high glucose the NEAT1 and DRP1 levels were upregulated, whereas the miR-150-5p level was downregulated in HK-2 cells. Knockdown of NEAT1 or DRP1 in high glucose-challenged HK-2 cells inhibited excessive reactive oxygen species production and lactate dehydrogenase release, increased cell viability, mitochondrial membrane potential and superoxide dismutase activity and enhanced mitophagy. Inhibition of miR-150-5p resulted in the opposite results. Mechanistically, NEAT1 sponged miR-150-5p to increase the DRP1 level. Moreover, silencing of NEAT1 or DRP1 could counteract miR-150-5p inhibition-induced deleterious effects. Collectively, our findings indicate that NEAT1 facilitates high glucose-induced damage in HK-2 cells by suppressing mitophagy via the miR-150-5p-DRP 1 axis, which sheds light on a novel mechanism of DN.

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“…Both were reported to express SIRT1, yet its roles are not well known. For example, a study by Yi et al [24] focused on polycystic ovarian syndrome (PCOS), and KGN were used to specifically study the role of SIRT1 in mitophagy. Han et al [4] used COV434 and performed SIRT1 knockdown studies.…”

Section: Discussionmentioning

confidence: 99%

“…Information on the expression of SIRTs and their possible roles in GCTs remains circumstantial. KGN and COV434, i.e., cell lines derived from GCTs, used in some related studies [4,7,24], express SIRT1. In particular, KGN cells [25] are widely used as an in vitro cell culture model of common, adult GCTs [26,27].…”

Section: Introductionmentioning

confidence: 99%

Sirtuin 1 and Sirtuin 3 in Granulosa Cell Tumors

Schmid¹,

Dietrich²,

Forné³

et al. 2021

IJMS

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Sirtuins (SIRTs) are NAD+-dependent deacetylases that regulate proliferation and cell death. In the human ovary, granulosa cells express sirtuin 1 (SIRT1), which has also been detected in human tumors derived from granulosa cells, i.e., granulosa cell tumors (GCTs), and in KGN cells. KGN cells are an established cellular model for the majority of GCTs and were used to explore the role of SIRT1. The SIRT1 activator SRT2104 increased cell proliferation. By contrast, the inhibitor EX527 reduced cell numbers, without inducing apoptosis. These results were supported by the outcome of siRNA-mediated silencing studies. A tissue microarray containing 92 GCTs revealed nuclear and/or cytoplasmic SIRT1 staining in the majority of the samples, and also, SIRT2-7 were detected in most samples. The expression of SIRT1–7 was not correlated with the survival of the patients; however, SIRT3 and SIRT7 expression was significantly correlated with the proliferation marker Ki-67, implying roles in tumor cell proliferation. SIRT3 was identified by a proteomic analysis as the most abundant SIRT in KGN. The results of the siRNA-silencing experiments indicate involvement of SIRT3 in proliferation. Thus, several SIRTs are expressed by GCTs, and SIRT1 and SIRT3 are involved in the growth regulation of KGN. If transferable to GCTs in situ, these SIRTs may represent novel drug targets.

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Melatonin ameliorates excessive PINK1/Parkin-mediated mitophagy by enhancing SIRT1 expression in granulosa cells of PCOS

Cited by 95 publications

References 40 publications

Melatonin Act as an Antidepressant via Attenuation of Neuroinflammation by Targeting Sirt1/Nrf2/HO-1 Signaling

Melatonin Act as an Antidepressant via Attenuation of Neuroinflammation by Targeting Sirt1/Nrf2/HO-1 Signaling

LncRNA NEAT1 accelerates renal tubular epithelial cell damage by modulating mitophagy via miR‐150‐5p–DRP1 axis in diabetic nephropathy

Sirtuin 1 and Sirtuin 3 in Granulosa Cell Tumors

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