Targeted activation of AMPK by GSK621 ameliorates H2O2-induced damages in osteoblasts

Liu, Weidong; Li, Mao; Feng, Jian; Chen, Fengli; Hao, Yuedong; Liu, Gang

doi:10.18632/oncotarget.14454

Cited by 36 publications

(41 citation statements)

References 40 publications

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“…As described in our previous studies [ 33 , 34 ], RNA was isolated from frozen liver tissues with Trizol reagents (Invitrogen, Shanghai, China). Quantitative real-time PCR (“qRT-PCR”) reactions were performed via the SYBR green kit through the ABI-7600 PCR system (Applied Biosystems).…”

Section: Methodsmentioning

confidence: 99%

Insulin resistance in vitamin D-deficient mice is alleviated by n-acetylcysteine

Cui

et al. 2017

Oncotarget

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Vitamin D deficiency will lead to insulin resistance. In the current study, vitamin D3 1α-Hydroxylase [“1α(OH)ase”] knockout mice were generated to mimic vitamin D deficiency in vivo. As compared to the wild-type mice, the liver tissues of the knockout mice showed impaired insulin signaling, decreased glucose transporter 4 expression and increased reactive oxygen species production. Meanwhile, p53-p21 activation, apoptosis intensity and pro-inflammatory cytokines (IL-6, IL-1 and MIP-1α) level were significantly increased in the knockout mice livers. Significantly, such effects in the knockout mice were largely attenuated by supplement with anti-oxidant n-acetylcysteine (NAC). Remarkably, insulin resistance and metabolic abnormalities in the knockout mice were largely alleviated after treatment of NAC. Therefore, inhibition of oxidative stress by NAC alleviated insulin resistance in vitamin D-deficient mice. Oxidative stress could be the primary cause of insulin resistance by vitamin D deficiency.

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Section: Methodsmentioning

confidence: 99%

Insulin resistance in vitamin D-deficient mice is alleviated by n-acetylcysteine

Cui

et al. 2017

Oncotarget

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“…Studies have shown that AMPK activation can inhibit Dex-induced ROS production [4,30,31,49,50]. Activated AMPK can increase NADPH content and activity to attenuate oxidative stress [49,51].…”

Section: Lnc-malat1 Inhibits Dex-induced Oxidative Stress In Human Osmentioning

confidence: 99%

Long Non-Coding RNA MALAT1 Protects Human Osteoblasts from Dexamethasone-Induced Injury via Activation of PPM1E-AMPK Signaling

Fan¹,

Zhang²,

Liu³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Dexamethasone (Dex) induces injuries to human osteoblasts. In this study, we tested the potential role of the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (Lnc-MALAT1) in this process. Materials: Two established human osteoblastic cell lines (OB-6 and hFOB1.19) and primary human osteoblasts were treated with Dex. Lnc-MALAT1 expression was analyzed by quantitative real-time polymerase chain reaction assay. Cell viability, apoptosis, and death were tested by the MTT assay, histone-DNA assay, and trypan blue staining assay, respectively. AMP-activated protein kinase (AMPK) signaling was evaluated by western blotting and AMPK activity assay. Results: Lnc-MALAT1 expression was downregulated by Dex treatment in the established osteoblastic cell lines (OB-6 and hFOB1.19) and primary human osteoblasts. The level of Lnc-MALAT1 was decreased in the necrotic femoral head tissues of Dex-administered patients. In osteoblastic cells and primary human osteoblasts, forced overexpression of Lnc-MALAT1 using a lentiviral vector (LV-MALAT1) inhibited Dex-induced cell viability reduction, cell death, and apoptosis. Conversely, transfection with Lnc-MALAT1 small interfering RNA aggravated Dex-induced cytotoxicity. Transfection with LV-MALAT1 downregulated Ppm1e (protein phosphatase, Mg^2+/ Mn²⁺-dependent 1e) expression to activate AMPK signaling. Treatment of osteoblasts with AMPKα1 short hairpin RNA or dominant negative mutation (T172A) abolished LV-MALAT1-induced protection against Dex-induced cytotoxicity. Furthermore, LV-MALAT1 induced an increase in nicotinamide adenine dinucleotide phosphate activity and activation of Nrf2 signaling. Dex-induced reactive oxygen species production was significantly attenuated by LV-MALAT1 transfection in osteoblastic cells and primary osteoblasts. Conclusion: Lnc-MALAT1 protects human osteoblasts from Dex-induced injuries, possibly via activation of Ppm1e-AMPK signaling.

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“…As described previously [ 16 , 40 , 54 – 56 ], we utilized the dichloro-dihydro-fluorescein diacetate (DCFH-DA) fluorescent dye (Invitrogen) assay to determine the intracellular ROS intensity. Briefly, after the applied treatment, DCFH-DA dye (5.0 μg/mL) was added to cells, followed by three-founds wash in warm PBS.…”

Section: Methodsmentioning

confidence: 99%

“…In vitro studies have been adding H 2 O 2 to the cultured human osteoblasts to establish a cellular model of osteoporosis/osteonecrosis [ 7 – 10 ]. This model would help to understand the pathological mechanisms of ROS-induced osteoblast injuries, and to develop possible intervention strategies [ 11 – 16 ].…”

Section: Introductionmentioning

confidence: 99%

microRNA-455 targets cullin 3 to activate Nrf2 signaling and protect human osteoblasts from hydrogen peroxide

et al. 2017

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Over-production of hydrogen peroxide (H2O2) will lead to human osteoblast dysfunction and apoptosis, causing progression of osteoporosis and osteonecrosis. NF-E2-related factor 2 (Nrf2) is a well-characterized anti-oxidant signaling. Cullin 3 (Cul3) ubiquitin E3 ligase dictates Nrf2 degradation. We demonstrate that microRNA-455 (“miR-455”) is a putative Cul3-targeting microRNA. Forced-expression of miR-455 in both hFOB1. 19 osteoblast cell line and primary human osteoblasts induced Cul3 degradation and Nrf2 protein stabilization, which led to subsequent transcription of ARE (anti-oxidant response element)-dependent genes (NQO1, HO1 and GCLC). Cul3 silencing, by expressing miR-455 or targeted-shRNA, protected human osteoblasts from H2O2. Reversely, miR-455 anti-sense caused Cul3 accumulation and Nrf2 degradation, which exacerbated H2O2 damages in hFOB1. 19 cells. Moreover, forced over-expression of Cul3 in hFOB1. 19 cells silenced Nrf2 and sensitized H2O2. Together, we propose that miR-455 activated Nrf2 signaling and protected human osteoblasts from oxidative stress possibly via targeting Cul3.

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Targeted activation of AMPK by GSK621 ameliorates H2O2-induced damages in osteoblasts

Cited by 36 publications

References 40 publications

Insulin resistance in vitamin D-deficient mice is alleviated by n-acetylcysteine

Insulin resistance in vitamin D-deficient mice is alleviated by n-acetylcysteine

Long Non-Coding RNA MALAT1 Protects Human Osteoblasts from Dexamethasone-Induced Injury via Activation of PPM1E-AMPK Signaling

microRNA-455 targets cullin 3 to activate Nrf2 signaling and protect human osteoblasts from hydrogen peroxide

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