αMSH prevents ROS-induced apoptosis by inhibiting Foxo1/mTORC2 in mice adipose tissue

Cao, Weina; Li, Meihang; Wu, Tianjiao; Fu, Feng; Feng, Tongying; Xu, Yang; Sun, Cheng

doi:10.18632/oncotarget.16606

Cited by 19 publications

(15 citation statements)

References 45 publications

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“…ROS is a collective term for various short-lived oxygen-containing molecules that are highly reactive and can promote oxidative stress [27]. They are the byproducts of aerobic respiration, and primarily arise from the mitochondria; excessive ROS production can cause damage to the mitochondria [28, 29].…”

Section: Resultsmentioning

confidence: 99%

Palmitic Acid-Induced Podocyte Apoptosis via the Reactive Oxygen Species-Dependent Mitochondrial Pathway

Liu

Chen

Sun

et al. 2018

Kidney Blood Press Res

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Background/Aims: Chronic kidney disease (CKD) is often accompanied by hyperlipidemia, which accelerates progression of the disease. Podocyte injury can lead to dysfunction of the glomerular filtration barrier, which is associated with proteinuria, a risk marker for the progression of CKD. Our previous studies demonstrated that palmitic acid (PA) can induce podocyte apoptosis; however, the underlying mechanisms are unclear. In the present study, we investigated the specific molecular mechanisms of PA-induced apoptosis in cultured podocytes. Methods: We cultured mouse podocytes and treated them with PA. Then, cell viability was measured using the Cell Counting Kit-8 colorimetric assay, lipid uptake was assessed by Oil Red O staining and boron-dipyrromethene staining, apoptosis was measured by flow cytometry, mitochondrial injury was assessed by JC-1 staining and transmission electron microscopy, and mitochondrial production of reactive oxygen species (ROS) was evaluated by fluorescence microscopy using the MitoSOX Red reagent. The effects of PA on the mitochondria-mediated caspase activation pathway were investigated by examining the expression of caspase-8, cleaved caspase-9, cleaved caspase-3, cleaved poly (ADP-ribose) polymerase (PARP), B-cell lymphoma 2 (Bcl-2), Bax, Bid, cytochrome c, and Fas-associated protein with death domain (FADD) using western blotting. The translocation of Bax and cytochrome c were detected by immunofluorescence. Results: PA treatment significantly increased lipid accumulation and induced podocyte apoptosis. We investigated whether the two primary apoptosis signaling pathways (death receptor-mediated pathway and mitochondria-mediated pathway) were involved in the execution of PA-induced podocyte apoptosis, and found that the levels of FADD, caspase-8, and Bid did not significantly change during this process. Meanwhile, PA treatment induced an increase in Bax protein expression and a decrease in Bcl-2 protein expression, with Bax translocation to the mitochondria. Furthermore, PA treatment induced mitochondrial impairment, and triggered the release of cytochrome c from the mitochondria to cytosol, with a concomitant dose-dependent increase in the levels of cleaved caspase-9, cleaved caspase-3, and PARP. Meanwhile, PA treatment increased mitochondrial production of ROS, and the mitochondria-targeted antioxidant mitoTEMPO significantly ameliorated PA-induced podocyte apoptosis. Conclusion: Our findings indicated that PA induced caspase-dependent podocyte apoptosis through the mitochondrial pathway, and mitochondrial ROS production participated in this process, thus potentially contributing to podocyte injury

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Section: Resultsmentioning

confidence: 99%

Palmitic Acid-Induced Podocyte Apoptosis via the Reactive Oxygen Species-Dependent Mitochondrial Pathway

Liu

Chen

Sun

et al. 2018

Kidney Blood Press Res

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“…However, drug treatment has too many unacceptable Considering these problems, inducing apoptosis to reduce adipocyte number may be an effective approach for obesity treatment. Our previous studies have shown that regulation of apoptosis in adipose tissue has the potential to form the basis of a future treatment of obesity (31)(32)(33)(34)(35).…”

Section: Discussionmentioning

confidence: 99%

miR-103/107 promote ER stress-mediated apoptosis via targeting the Wnt3a/β-catenin/ATF6 pathway in preadipocytes

Zhang

Saeed

et al. 2018

Journal of Lipid Research

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Both miR-103 and miR-107 have been demonstrated to restrain cell proliferation and regulate lipid metabolism and inflammation. However, the effects of miR-103/107 on preadipocyte apoptosis remain unknown. In the present research, we have investigated how miR-103/107 regulated preadipocyte apoptosis. We found that miR-103/107 aggravated endoplasmic reticulum (ER) stress-mediated apoptosis in preadipocytes. We confirmed that miR-103/107 targeted WNT family member 3a (Wnt3a) in preadipocytes. It was found that overexpressing Wnt3a resulted in suppression of ER stress-mediated apoptosis, while restoration of miR-103/107 counteracted the effects of Wnt3a in preadipocytes. Moreover, bioinformatics and luciferase assays indicated that activating transcription factor (ATF)6 is a key player linking miR-103/107-induced ER stress to apoptosis. is regulated by lymphoid enhancer-binding factor 1, a transcription factor downstream of the Wnt3a/β-catenin signaling pathway, and ATF6 binds to the B-cell lymphoma 2 () promoter to regulate apoptosis further. In conclusion, miR-103/107 promoted ER stress-mediated apoptosis by targeting the Wnt3a/β-catenin/ATF6 signaling pathway in preadipocytes. This study revealed that the miR-103/107-Wnt3a/β-catenin-ATF6 pathway is critical to the progression of apoptosis in preadipocytes, which suggested that approaches to activate miR-103/107 could potentially be useful as new therapies for treating obesity and metabolic syndrome-related disorders.

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“…HEK293T cells also co-transfected with Fabp4 promoter plasmid and pc-Hoxa5 plasmid or pcDNA3.1 plasmid. The experimental protocols were followed as previous described [17]. …”

Section: Methodsmentioning

confidence: 99%

Hoxa5 Promotes Adipose Differentiation via Increasing DNA Methylation Level and Inhibiting PKA/HSL Signal Pathway in Mice

Cao

Luo

Saeed

et al. 2018

Cell Physiol Biochem

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Background/Aims: Impaired adipogenesis may be the underlying cause in the development of obesity and type II diabetes. Mechanistically, the family of Homeobox transcription factors is implicated in the regulation of adipocyte fate. Hoxa5 is highly expressed in adipocytes, and its mRNA expression is decreased during differentiation. However, the function of Hoxa5 in adipose tissue has been poorly understood. The aim of this study is to unveil the role of Hoxa5 on adipocyte differentiation and its underlying mechanisms. Methods: Quantitative real-time PCR (qPCR) and western blot were performed to determine Hoxa5 expression in primary adipocytes and in adipose tissues from mice. Lipid accumulation was evaluated by bodipy staining. Dual luciferase assay was applied to explore the transcription factor of Hoxa5 and the transcriptional target gene modulated by Hoxa5. All measurements were performed at least for three times at least. Results: A significant reduction of Hoxa5 expression was observed in adipose tissue of High Fat Diet (HFD) induced obesity mice. We determined Hoxa5 increased adipocytes differentiation and mitochondrial biogenesis in adipocytes in vitro. CEBPβ was determined a transcription factor of Hoxa5 and inhibited methylation level of Hoxa5 by combining on the promoter of Hoxa5. Importantly, we found Fabp4, a known positive regulator of adipocytes differentiation, was transcriptional activation by Hoxa5. In addition, Hoxa5 promotes adipocytes differentiation by inhibiting PKA/HSL pathway. Conclusion: Our study demonstrated the promoting role of Hoxa5 in adipocytes differentiation and therefore bringing a new therapeutic mean to the treatment of obesity and type II diabetes.

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αMSH prevents ROS-induced apoptosis by inhibiting Foxo1/mTORC2 in mice adipose tissue

Cited by 19 publications

References 45 publications

Palmitic Acid-Induced Podocyte Apoptosis via the Reactive Oxygen Species-Dependent Mitochondrial Pathway

Palmitic Acid-Induced Podocyte Apoptosis via the Reactive Oxygen Species-Dependent Mitochondrial Pathway

miR-103/107 promote ER stress-mediated apoptosis via targeting the Wnt3a/β-catenin/ATF6 pathway in preadipocytes

Hoxa5 Promotes Adipose Differentiation via Increasing DNA Methylation Level and Inhibiting PKA/HSL Signal Pathway in Mice

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