TREK‑TRAAK two‑pore domain potassium channels protect human retinal pigment epithelium cells from oxidative stress

Huang, Hao; Han, Li; Shi, Kangpei; Wang, Lei; Zhang, Xiaolin; Zhu, Xiaobo

doi:10.3892/ijmm.2018.3813

Cited by 9 publications

(6 citation statements)

References 27 publications

(27 reference statements)

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“…Fluoxetine is a small molecule that mimics neurotrophic signalling (31). One study showed that fluoxetine has a protective effect on retinal epithelial cells (32). Other studies have shown that fluoxetine promotes the recovery of synaptic proteins in the visual cortex (33,34).…”

Section: Discussionmentioning

confidence: 99%

Differential Expression of BDNF and BIM in Streptozotocin-induced Diabetic Rat Retina After Fluoxetine Injection

Kim

Chung

Hwang

et al. 2021

In Vivo

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Background: Chronic diabetic retinopathy (DR) is a diabetic complication that causes blindness. Brainderived neurotrophic factor (BDNF) expression is induced by fluoxetine. We observed the effects of fluoxetine on a streptozotocin (STZ)-induced diabetic rat model in this study. Materials and Methods: Rats were divided into three groups: Control, diabetic (65 mg/kg STZ injection), and diabetic with fluoxetine injection (20 mg/kg/week, six times). Western blotting was performed using anti-BDNF and anti-hexaribonucleotide-binding protein-3. Expression of BCL2 apoptosis regulator-like protein 11 (BIM) was analysed using a reverse transcription-polymerase chain reaction. Results: BDNF levels were significantly higher in the diabetic group treated with fluoxetine than in the untreated diabetic group. BIM expression was higher in the diabetic group than in the control group. BIM gene expression was lower in fluoxetinetreated diabetic group than in the untreated diabetic group. Conclusion: Fluoxetine had an anti-apoptotic effect with upregulation of BDNF expression in retina of rats with STZinduced diabetes.Diabetic retinopathy (DR) is a complication of diabetes that causes blindness (1). Important mechanisms of blindness are macular edema and alteration of neovascularisation (2, 3). Vascular endothelial growth factor (VEGF) is the most effective mediator of DR progression (4). Anti-VEGF effects are associated with the regression of retinal neovascularisation (5) and anti-VEGF treatment is the most effective approach for DR therapy. However, some patients show poor response to this treatment (6). Thus, comprehension of the pathogenesis of DR is critical. Although DR is traditionally known as a vascular disease, some studies have shown that neuronal pathological changes occur in the retina, including physiological and structural alterations (7, 8).Brain-derived neurotrophic factor (BDNF) is a neuroprotective growth factor that affects neuronal cell proliferation and survival (9). BDNF binds to tropomyosin receptor kinase B (TRKB), which leads to nerve cell survival, repair, and development through the neurotrophic signalling pathway (10). BDNF has also been observed in retinal neuronal cells. BDNF is expressed in retinal ganglion cells (RGCs) and was found to play an important role in their survival in rats with streptozotocin (STZ)-induced diabetes (11). Cusato et al. reported that BDNF prevented cell death in the inner nuclear layer of the retina (12). Uzel et al. showed that BDNF is a good marker for the early diagnosis of DR (13).In a previous study, BDNF expression was induced by fluoxetine, a selective inhibitor of serotonin reuptake, to treat major depression (14). In this study, we analysed the expression of BDNF and BCL2 apoptosis regulator-like protein 11 (BIM) after fluoxetine injection in the STZinduced diabetes rat model to investigate the effect of fluoxetine on BDNF signalling. Materials and MethodsRat model of DR. All animal studies were approved by the Chosun University Institutional Animal Care and Use C...

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Section: Discussionmentioning

confidence: 99%

Differential Expression of BDNF and BIM in Streptozotocin-induced Diabetic Rat Retina After Fluoxetine Injection

Kim

Chung

Hwang

et al. 2021

In Vivo

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“…At last, all of the RPE cells were co-stained with annexin V and PI to record the fluorescence intensity. 78 …”

Section: Methodsmentioning

confidence: 99%

PSCs Reveal PUFA-Provoked Mitochondrial Stress as a Central Node Potentiating RPE Degeneration in Bietti’s Crystalline Dystrophy

et al. 2020

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Bietti’s crystalline dystrophy (BCD) is an incurable retinal disorder caused by the polypeptide 2 of cytochrome P450 family 4 subfamily V ( CYP4V2 ) mutations. Patients with BCD present degeneration of retinal pigmented epithelial (RPE) cells and consequent blindness. The lack of appropriate disease models and patients’ RPE cells limits our understanding of the pathological mechanism of RPE degeneration. In this study, using CYP4V2 mutant pluripotent stem cells as disease models, we demonstrated that RPE cells with CYP4V2 mutations presented a disrupted fatty acid homeostasis, which were characterized with excessive accumulation of poly-unsaturated fatty acid (PUFA), including arachidonic acid (AA) and eicosapentaenoic acid (EPA). The PUFA overload increased mitochondrial reactive oxygen species, impaired mitochondrial respiratory functions, and triggered mitochondrial stress-activated p53-independent apoptosis in CYP4V2 mutant RPE cells. Restoration of the mutant CYP4V2 using adeno-associated virus 2 (AAV2) can effectively reduce PUFA deposition, alleviate mitochondria oxidative stresses, and rescue RPE cell death in BCD RPE cells. Taken together, our results highlight a role of PUFA-induced mitochondrial damage as a central node to potentiate RPE degeneration in BCD patients. AAV2-mediated gene therapy may represent a feasible strategy for the treatment of BCD.

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“…Mean intensity fluorescence was measured with a green laser (430 nm) while using Flow Cytometer Guava easyCyte (Merck Millipore, Darmstadt, Germany). Incubations with only secondary antibody were used as the negative controls [47].…”

Section: Methodsmentioning

confidence: 99%

Effect of 6-Shogaol on the Glucose Uptake and Survival of HT1080 Fibrosarcoma Cells

et al. 2019

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Ginger is a plant that is native to southern China. In the last decade and research on the components of ginger has significantly increased; of these components, 6-shogaol exhibits the greatest potential antitumor capacity. However, the molecular mechanism through which 6-shogaol exerts its effects has not yet been elucidated. In this study, the effect of 6-shogaol on tumor cells that were derived from human fibrosarcoma (HT1080) was evaluated. Cell viability was determined by a (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay testing different concentrations of 6-shogaol (2.5–150 μM). Subsequently, the effect of 6-shogaol on reactive oxygen species (ROS) production, glucose uptake, and protein expression of the signaling pathway phosphatase and tensin homolog/ protein kinase B /mammalian target of rapamycin (PTEN/Akt/mTOR) was measured. 6-Shogaol reduced the viability of the tumor cells and caused an increase in ROS production, which was attenuated with the addition of N-acetylcysteine, and the recovery of cell viability was observed. The increase in ROS production in response to 6-shogaol was associated with cell death. Similarly, glucose uptake decreased with incremental concentrations of 6-shogaol, and an increase in the expression of mTOR-p and Akt-p proteins was observed; PTEN was active in all the treatments with 6-shogaol. Thus, the results suggest that cells activate uncontrolled signaling pathways, such as phosphoinositide 3-kinase (PI3K)/Akt/mTOR, among other alternative mechanisms of metabolic modulation and of survival in order to counteract the pro-oxidant effect of 6-shogaol and the decrease in glucose uptake. Interestingly, a differential response was observed when non-cancerous cells were treated with 6-shogaol.

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TREK‑TRAAK two‑pore domain potassium channels protect human retinal pigment epithelium cells from oxidative stress

Cited by 9 publications

References 27 publications

Differential Expression of BDNF and BIM in Streptozotocin-induced Diabetic Rat Retina After Fluoxetine Injection

Differential Expression of BDNF and BIM in Streptozotocin-induced Diabetic Rat Retina After Fluoxetine Injection

PSCs Reveal PUFA-Provoked Mitochondrial Stress as a Central Node Potentiating RPE Degeneration in Bietti’s Crystalline Dystrophy

Effect of 6-Shogaol on the Glucose Uptake and Survival of HT1080 Fibrosarcoma Cells

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