Protective Effect of SGK1 in Rat Hippocampal Neurons Subjected to Ischemia Reperfusion

Zhang, Wei; Qian, Chuan yun; Li, Shu qing

doi:10.1159/000363000

Cited by 30 publications

(27 citation statements)

References 40 publications

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“…For experiments at normal culture conditions (21% oxygen and with glucose), the experiment medium was DMEM (glucose concentration at 5.5 mM). To achieve OGD, a technique was similar to that described by Iraburu and Li [23]. Briefly, the OGD experimental medium (DMEM without glucose) was previously gassed with nitrogen for 30 min and then added to cell culture wells, which had been washed three times with PBS.…”

Section: Methodsmentioning

confidence: 99%

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

Liu

You²,

Tu³

et al. 2015

Cell Physiol Biochem

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Background: There is an increasing interest in the role of astrocytes contributing to the intrinsic bioremediation of ischemic brain injury. The purpose of this study was to disclose the effects and mechanism of midazolam (MDZ) on the proliferation and apoptosis of astrocytes under oxygen glucose deprivation (OGD) condition. Methods: The astrocytes were assigned randomly into four groups: control group, OGD group, OGD+MDZ group, and OGD+MDZ+IL-6 group. The astrocytes were treated with MDZ at dose of 10 μmol/L in OGD+MDZ group. And in OGD+MDZ+IL-6 group, the astrocytes were treated with MDZ at dose of 10μmol/L and IL-6 at dose of 50 ng/mL. MTT assay was used to assess cell proliferation, and cell apoptosis was analyzed by TUNEL apoptosis assay kit and flow cytometry. Furthermore, the expression of JAK2, p-JAK2, STAT3, p-STAT3, Bcl-2, Bax and Caspase-3 proteins were determined by western blotting assay. Results: Astrocytes proliferation was decreased obviously in OGD group, while MDZ could increase astrocytes proliferation under OGD condition. Moreover, OGD could induce apoptosis in astrocytes and MDZ could play an anti-apoptotic role. However, IL-6, a JAK2 activator, could attenuate cell proliferation and anti-apoptotic effects of MDZ in astrocytes. In addition, the expression of Bcl-2 protein in MDZ group increased markedly, while the JAK2/STAT3 signal proteins, Bax and Caspase-3 proteins decreased relative to OGD group. But IL-6 could counteract the anti-apoptotic effects of MDZ. Conclusion: Midazolam has protective effects on the proliferation and apoptosis of astrocytes via JAK2/STAT3 signal pathway in vitro. We firstly disclose the beneficial roles of midazolam in astrocytes under ischemic condition, which may be a rational treatment selection for ischemic cerebral protection.

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Section: Methodsmentioning

confidence: 99%

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

Liu

You²,

Tu³

et al. 2015

Cell Physiol Biochem

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“…However, increased ROS production under aberrant metabolic processes leads to oxidative stress, which has been implicated in the pathophysiology of various neurological disorders [2][3][4]. It is well known that the mammalian brain has high amount of oxygen but low levels of antioxidant enzymes, making it particularly sensitive to oxidative damage [5,6].…”

Section: Introductionmentioning

confidence: 99%

FAM3A Protects HT22 Cells Against Hydrogen Peroxide-Induced Oxidative Stress Through Activation of PI3K/Akt but not MEK/ERK Pathway

Song¹,

Gou²,

Zhang³

2015

Cell Physiol Biochem

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Background/Aims: Oxidative stress-induced cell damage is involved in many neurological diseases. FAM3A is the first member of family with sequence similarity 3 (FAM3) gene family and its biological function remains largely unknown. Methods: This study aimed to determine its role in hydrogen peroxide (H₂O₂) induced injury in neuronal HT22 cells. The protective effects were measured by cell viability, lactate dehydrogenase (LDH) release and apoptosis, and oxidative stress was assayed by reactive oxygen species (ROS) generation, ATP synthesis and lipid peroxidation. By using selective inhibitors, the involvement of PI3K/Akt and MEK/ERK pathways were also investigated. Results: The results of fluorescence staining revealed that H₂O₂ significantly decreased the expression of FAM3A protein, which was shown to be subcellularly located in mitochondria. Up-regulation of FAM3A by lentivirus transfection markedly increased cell viability and decreased LDH release after H₂O₂ treatment. The anti-apoptotic activity of FAM3A was demonstrated by the reduced mitochondrial cytochrome c release, decreased activation of caspase-3 and the results of flow cytometry. Overexpression of FAM3A attenuated intracellular ROS generation and loss of ATP production induced by H₂O₂, and subsequently inhibited lipid peroxidation. In addition, overexpression of FAM3A significantly increased the activation of Akt and ERK in H₂O₂ injured HT22 cells. By using Akt and ERK specific inhibitors, we found that inhibition of PI3K/Akt, but not MEK/ERK pathway, partially prevented FAM3A-induced protection against H₂O₂. Conclusion: These results suggest that FAM3A has protective effects against H₂O₂-induced oxidative stress by reducing ROS accumulation and apoptosis, and these protective effects are dependent on the activation of PI3K/Akt pathway.

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“…SGK1 shares the latter substrate with Akt. Two recent studies have shown a neuroprotective role for SGK1 in a 6-hydroxydopamine (6-OHDA) neurotoxin mouse model and in an ischemia reperfusion rat model (13,14). These findings underscore the importance of SGK1 in neurodegeneration, but the details of signaling molecules that contribute to neuroprotection are not well defined.…”

mentioning

confidence: 99%

Serum- and Glucocorticoid-Inducible Kinase 1 Confers Protection in Cell-Based and in In Vivo Neurotoxin Models via the c-Jun N-Terminal Kinase Signaling Pathway

Iqbal

Howard

LoGrasso

2015

Molecular and Cellular Biology

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Serum glucocorticoid kinase 1 (SGK1) has been shown to be protective in models of Parkinson's disease, but the details by which it confers benefit is unknown. The current study was designed to investigate the details by which SGK1 confers neuroprotection. To do this we employed a cellular neurodegeneration model to investigate c-Jun N-terminal kinase (JNK) signaling and endoplasmic reticulum (ER) stress induced by 6-hydroxydopamine. SGK1-expressing adenovirus was created and used to overexpress SGK1 in SH-SY5Y cells, and dexamethasone was used to increase endogenous expression of SGK1. Oxidative stress, mitochondrial dysfunction, and cell death were monitored to test the protective effect of SGK1. To investigate the effect of SGK1 overexpression in vivo, SGK1-expressing adenovirus was injected into the striatum of mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and protection of dopaminergic neurons was quantitatively assessed by tyrosine hydroxylase immunohistochemistry. SGK1 overexpression was found to decrease reactive oxygen species generation, alleviate mitochondrial dysfunction, and rescue cell death in vitro and in vivo by inactivating mitogen-activated protein kinase kinase 4 (MKK4), JNK, and glycogen synthase kinase 3␤ (GSK3␤) and thereby decreasing ER and oxidative stress. These results suggest that therapeutic strategies for activation of SGK1 may have the potential to be neuroprotective by deactivating the JNK and GSK3␤ pathways.S erum-and glucocorticoid-inducible kinase 1 (SGK1) belongs to the AGC family of kinases and has been shown to have various cellular functions, including the promotion of cell survival (1-3). SGK1 is activated by insulin and growth factors via phosphoinositide 3-kinase (PI3K), 3-phosphoinositide-dependent kinase 1 (PDK1), and mammalian target of rapamycin complex 2 (mTORC2) (4, 5). SGK1 shares its functions and some substrates with another kinase from the AGC family, protein kinase B (PKB/ Akt). Akt, like SGK1, has been shown to mediate cell survival through various signaling cascades and gets activated by a wide range of extracellular stimuli (6). SGK1 lacks the pleckstrin homology (PH) domain that tethers Akt to the plasma membrane, making SGK1 more accessible to cytosolic and nuclear sites and thereby providing it with cellular functions and substrates that do not overlap those of Akt (1, 6). SGK1 plays a protective role in oxidative stress conditions as small interfering RNA (siRNA) knockdown of SGK1 has shown an increase in oxidative stressinduced cell death in HEK293 cells (7). Oxidative stress is a hallmark of neurodegenerative disorders, such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD) (8). In a study published in 2005 by Schoenebeck et al., upregulation of SGK1 was seen in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin model and in a transgenic model of ALS (SOD1-G93A), and protection from cell death was observed for animals treated with dexamethasone (De...

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Protective Effect of SGK1 in Rat Hippocampal Neurons Subjected to Ischemia Reperfusion

Cited by 30 publications

References 40 publications

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

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

FAM3A Protects HT22 Cells Against Hydrogen Peroxide-Induced Oxidative Stress Through Activation of PI3K/Akt but not MEK/ERK Pathway

Serum- and Glucocorticoid-Inducible Kinase 1 Confers Protection in Cell-Based and in In Vivo Neurotoxin Models via the c-Jun N-Terminal Kinase Signaling Pathway

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