Midazolam Inhibits the Apoptosis of Astrocytes Induced by Oxygen Glucose Deprivation via Targeting JAK2-STAT3 Signaling Pathway

Liu, Li; You, Qi; Tu, Yingfeng; Li, Quanyi; Zheng, Lihong; Li, Xuan; Gu, Jie; Wang, Guonian

doi:10.1159/000369681

Cited by 18 publications

(19 citation statements)

References 38 publications

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“…As shown in several previous studies, the JAK2-STAT3 signalling pathway regulates apoptosis-related genes, such as c-Caspase, Bcl-2, Bcl-x, Bax and Caspase-3 43, 44 . Additionally, one of the primary mechanisms responsible for the behavioural impairments induced by exposure to chronic stress may be related to excessive apoptosis 45, 46 .…”

Section: Discussionmentioning

confidence: 56%

Xiaoyaosan exerts anxiolytic-like effects by down-regulating the TNF-α/JAK2-STAT3 pathway in the rat hippocampus

Jiang

et al. 2017

Sci Rep

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Although the anxiolytic-like effects of Xiaoyaosan, a Chinese herbal formula, have been described in many previous studies, its underlying mechanism remains undefined. The cytokine tumour necrosis factor-α (TNF-α) and its closely associated janus kinase 2 (JAK2)-signal transducer and activator of transcription (STAT3) signalling pathway regulate the neuro-inflammatory response in the brain, thus participating in the development of anxiety. Our purpose was to investigate whether the anxiolytic-like effects of Xiaoyaosan are related to the TNF-α/JAK2-STAT3 pathway in the hippocampus. We examined the effects of Xiaoyaosan on behaviours exhibited in the elevated plus maze test, open field test and novelty-suppressed feeding test as well as hippocampal neuron damage and changes in the TNF-α/JAK2-STAT3 pathway in a rat model of chronic immobilization stress (CIS)-induced anxiety. Xiaoyaosan exerts anxiolytic-like effects on CIS-induced anxiety, with a significant alleviation of anxiety-like behaviours, an attenuation of hippocampal neuron damage, and a reversal of the activation of the TNF-α/JAK2-STAT3 pathway in the hippocampus that are similar to the effects of the JAK2 antagonist AG490. However, Xiaoyaosan and AG490 failed to effectively regulate apoptosis-related factors, including Bax and Caspase-3. These results suggest that Xiaoyaosan attenuates stress-induced anxiety behaviours by down-regulating the TNF-α/JAK2-STAT3 pathway in the rat hippocampus.

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Section: Discussionmentioning

confidence: 56%

Xiaoyaosan exerts anxiolytic-like effects by down-regulating the TNF-α/JAK2-STAT3 pathway in the rat hippocampus

Jiang

et al. 2017

Sci Rep

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“…Cell apoptosis was measured by flow cytometry analysis as described previously [22]. Treated cells were harvested and re-suspended in 2.5 ml phosphate buffered solution (PBS).…”

Section: Methodsmentioning

confidence: 99%

Neuroprotective Effects of Pycnogenol Against Oxygen-Glucose Deprivation/Reoxygenation-Induced Injury in Primary Rat Astrocytes via NF-κB and ERK1/2 MAPK Pathways

Xia¹,

Ji²,

Zhang³

2017

Cell Physiol Biochem

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Backgrounds/Aims: Pycnogenol (PYC) is a patented mix of bioflavonoids with potent anti-oxidant and anti-inflammatory properties. In this study, we investigated the effects of PYC on oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury in primary rat astrocytes. Methods: The primary rat astrocytes were randomly divided into 6 groups, blank control, OGD/R, OGD/R+PYC (10, 20, 40, and 60 µg/mL). The cell activity were detected by MTT and LDH assays, then the levels of oxidant products [malondialdehyde (MDA) and reactive oxygen species (ROS)] , antioxidants [superoxide dismutase (SOD)], mitochondrial membrane potential (MMP) and inflammatory cytokines were detected. In addition, the expression levels of apoptosis-related proteins (Bax, Bcl-2 and Cleaved caspase 3), proinflammatory factors (NF-κB p65), and p-ERK1/2 were measured by Western blot analysis. Results: The results showed that PYC incubation dose-dependently attenuated cell viability loss, LDH leakage, oxidative stress, inflammatory cytokines accumulation and cell apoptosis caused by OGD/R. Furthermore, PYC pretreatment dose-dependently suppressed OGD/R-induced NF-κB p65 nuclear translocation, NF-κB activity and ERK1/2 phosphorylation. Similarly to PYC, NF-κB inhibitor PDTC and ERK1/2 inhibitor PD098059 dramatically inhibited OGD/R-induced NF-κB activation, ERK1/2 phosphorylation, and ROS production, as well as TNF-α secretion. Conclusions: These findings revealed that PYC has neuroprotective effects against OGD/R-induced injury via NF-κB and ERK1/2 pathways in primary rat astrocytes.

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“…Study found that both CLA (conjugated linoleic acid)-isomers increased TNF and IL-6 mRNA in primary astrocyte cultures indicate that astrocytes may contribute to neuronal inflammation [23]. It also showed that IL-6 could attenuate cell proliferation and anti-apoptotic effects of MDZ in astrocytes [24]. Thus, in this experiment we used IL-17 to stimulate the astrocytes cultured in vitro and to investigate the relationship of several inflammatory cytokines and chemokines, including regulatory proteins, which might provide a theoretical basis for anti-inflammatory therapy of SCI in clinic.…”

Section: Discussionmentioning

confidence: 96%

The Effects of Interleukin-17 (IL-17)-Related Inflammatory Cytokines and A20 Regulatory Proteins on Astrocytes in Spinal Cord Cultured In Vitro

Zong

Zeng

et al. 2016

Cell Physiol Biochem

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Background/Aims: This study focused on investigating the expression of several inflammatory cytokines and chemokines, including regulatory proteins in the astrocytes of mice stimulated with IL-17. Materials and Methods: The cultured astrocytes from the spinal cords of mice were stimulated with IL-17. The expression of interleukin-6 (IL-6), tumor necrosis factor (TNF), monocyte chemotactic protein-1/5 (MCP-1/5) and macrophage inflammatory protein-2 (MIP-2) stimulated with IL-17 (50 ng/ml) at different time points (3 h, 6 h, 12 h, 24 h and 48 h) were determined using real-time PCR and ELISA. The expressions of A20 (tumor necrosis factor a inducible protein 3, TNFAIP3) and NF-κB were examined using real-time PCR and western blotting. Results: Compared with the control group, the mRNA expression levels of IL-6, TNF, MCP-1/5 and MIP-2 increased significantly at 6 h after IL-17 stimulation, while the protein expression levels also increased significantly and peaked at 12 h. The mRNA expression level of NF-κB increased and peaked at 6 h before gradually declining, while the expression of A20 decreased. The protein expression level of NF-κB increased and peaked at 12 h, while the expression A20 had an opposite response. Conclusion: The study showed that NF-κB may have an effect on the cytokines secreted by astrocytes after IL-17 stimulation. Moreover, both A20 and NF-κB could regulate the expression and secretion of inflammatory mediators.

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Midazolam Inhibits the Apoptosis of Astrocytes Induced by Oxygen Glucose Deprivation via Targeting JAK2-STAT3 Signaling Pathway

Cited by 18 publications

References 38 publications

Xiaoyaosan exerts anxiolytic-like effects by down-regulating the TNF-α/JAK2-STAT3 pathway in the rat hippocampus

Xiaoyaosan exerts anxiolytic-like effects by down-regulating the TNF-α/JAK2-STAT3 pathway in the rat hippocampus

Neuroprotective Effects of Pycnogenol Against Oxygen-Glucose Deprivation/Reoxygenation-Induced Injury in Primary Rat Astrocytes via NF-κB and ERK1/2 MAPK Pathways

The Effects of Interleukin-17 (IL-17)-Related Inflammatory Cytokines and A20 Regulatory Proteins on Astrocytes in Spinal Cord Cultured In Vitro

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