High-glucose Induces Retinal Pigment Epithelium Mitochondrial Pathways of Apoptosis and Inhibits Mitophagy by Regulating ROS/PINK1/Parkin Signal Pathway

Yang, Yanni; Xu, Zhiyun; Yuan, Yunfei; Xi, Xiaoting; Yan, Mingxia; Zhao, Xueying; Zhou, Liqiong; Ma, Minjun; Liu, Sili

doi:10.1101/420653

Cited by 8 publications

(9 citation statements)

References 38 publications

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“…In HG-induced retinal pigment epithelium in a dosedependent manner, HG promoted reactive oxygen species (ROS) production and apoptosis and inhibited autophagy and proliferation, while low glucose induced ROS production and autophagy but had little effect on apoptosis and proliferation (43). Consistent with the literature, this research found that participants who reported using HG-induced retinal pigment epithelium played an important role in the development of DR.…”

Section: Discussionsupporting

confidence: 83%

Secreted Protein Acidic and Rich in Cysteine Mediates the Development and Progression of Diabetic Retinopathy

et al. 2022

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BackgroundsDiabetic retinopathy (DR) is one of the most severe microvascular complications of diabetes mellitus (DM). Secreted protein acidic and rich in cysteine (SPARC) has been found to play an important role in many diseases, but its role and mechanism in DR remain unknown.MethodsWe studied the role of SPARC and integrin β1 in vascular pathophysiology and identified potential therapeutic translation. The SPARC levels were tested in human serum and vitreous by ELISA assay, and then the Gene Expression Omnibus (GEO) dataset was used to understand the key role of the target gene in DR. In human retinal capillary endothelial cells (HRCECs), we analyzed the mRNA and protein level by RT-PCR, immunohistochemistry, and Western blotting. The cell apoptosis, cell viability, and angiogenesis were analyzed by flow cytometry, CCK-8, and tube formation.ResultsIn this study, we investigated the role of SPARC in the development and progression of human DR and high glucose-induced HRCEC cells and found that the SPARC-ITGB1 signaling pathway mimics early molecular and advanced neurovascular pathophysiology complications of DR. The result revealed that DR patients have a high-level SPARC expression in serum and vitreous. Knockdown of SPARC could decrease the expressions of inflammatory factors and VEGFR, inhibit cell apoptosis and angiogenesis, and increase cell viability by regulating integrin β1 in HRCECs.ConclusionSPARC promotes diabetic retinopathy via the regulation of integrin β1. The results of this study can provide a potential therapeutic application for the treatment of DR.

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Section: Discussionsupporting

confidence: 83%

Secreted Protein Acidic and Rich in Cysteine Mediates the Development and Progression of Diabetic Retinopathy

et al. 2022

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“…CSE-induced insufficient mitophagy and abundant damaged mitochondria are frequently caused by oxidative stress [23]. After CSE exposure, ROS increased, whereas the activities of T-SOD and GSH-PX were downregulated in BEAS-2B cells.…”

Section: Ecc-byf III Improved Cse-induced Oxidative Stress In Beas-2b...mentioning

confidence: 99%

Effective-component compatibility of Bufei Yishen formula III ameliorated COPD by improving airway epithelial cell senescence by promoting mitophagy via the NRF2/PINK1 pathway

Qin

Tian

et al. 2022

BMC Pulm Med

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Background Effective-component compatibility of Bufei Yishen formula III (ECC-BYF III) demonstrates positive effects on stable chronic obstructive pulmonary disease (COPD). Purpose To investigate the mechanisms of ECC-BYF III on COPD rats from the aspect of airway epithelial cell senescence. Methods COPD model rats (Sprague-Dawley rat) were treated with ECC-BYF III for 8 weeks, and the efficacy was evaluated. Cigarette smoke extract (CSE)-induced senescence model of airway epithelial cells was treated with ECC-BYF III, and related enzymes and proteins involved in oxidative stress and mitophagy were detected. Results ECC-BYF III markedly rescued pulmonary function and histopathological changes, which might be associated with the amelioration of lung senescence, including the reduction of malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and matrix metalloproteinase (MMP)-9 levels, increase of the level in total superoxide dismutase (T-SOD), and decease in the p21 level in the airways. Furthermore, ECC-BYF III suppressed p16 and p21 expressions and senescence-associated β-galactosidase (SA-β-Gal) in CSE-induced airway epithelial cells. Moreover, ECC-BYF III upregulated mitophagy-related proteins, including the co-localizations of TOM20 and LC3B, PINK1 and PARK2, and improved mitochondrial function by upregulating mitochondrial mitofusin (MFN)2 and reducing dynamin-related protein 1 (DRP1) expression. ECC-BYF III enhanced the activities of T-SOD and GSH-PX by up-regulating NRF2, thus inhibiting oxidative stress. After intervention with NRF2 inhibitor, the regulation effects of ECC-BYF III on oxidative stress, mitophagy and senescence in airway epithelial cells were significantly suppressed. Conclusions ECC-BYF III exerts beneficial effects on COPD rats by ameliorating airway epithelial cell senescence, which is mediated by inhibiting oxidative stress and subsequently enhancing mitophagy through the activation of NRF2 signaling.

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“…As there is little research on effects of high glucose concentration on fish cells in vitro, the present study referred the literatures from other species (19)(20)(21)(22)(23)(24)(25) . The treatment of high glucose on cells usually used the medium containing 20 mM, 25 mM, 33 mM or 50 mM of glucose.…”

Section: Glucose Concentration In Medium Of High Glucose Conditionmentioning

confidence: 99%

High glucose induces apoptosis, glycogen accumulation and suppresses protein synthesis in muscle cells of olive flounder Paralichthys olivaceus

et al. 2021

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The effect and the mechanism of high glucose on fish muscle cells are not fully understood. In the present study, muscle cells of olive flounder (Paralichthys olivaceus) were treated with high glucose (33 mM) in vitro. Cells were incubated in three kinds of medium containing 5 mM glucose, 5 mM glucose and 28 mM mannitol (as an isotonic contrast) or 33 mM glucose named the Control group, the Mannitol group and the HG (high glucose) group, respectively. Results showed that high glucose increased the ADP/ATP ratio and the reactive oxygen species (ROS) level, decreased mitochondrial membrane potential (MMP), induced the release of cytochrome C (CytC) and cell apoptosis. High glucose also led to cell glycogen accumulation by increasing the glucose uptake ability and affecting the mRNA expressions of glycogen synthase and glycogen phosphorylase. Meanwhile, it activated AMP-activated protein kinase (AMPK), inhibited the activity of mammalian target of rapamycin (mTOR) signaling pathway and the expressions of myogenic regulatory factors (MRFs). The expressions of myostatin-1 (mstn-1) and E3 ubiquitin ligases including muscle RING-finger protein 1 (murf-1) and muscle atrophy F-box protein (mafbx) were also increased by the high glucose treatment. No difference was found between the Mannitol group and the Control group. These results demonstrate that high glucose has the effects of inducing apoptosis, increasing glycogen accumulation and inhibiting protein synthesis on muscle cells of olive flounder. The mitochondria mediated apoptotic signaling pathway, AMPK and mTOR pathways participated in these biological effects.

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High-glucose Induces Retinal Pigment Epithelium Mitochondrial Pathways of Apoptosis and Inhibits Mitophagy by Regulating ROS/PINK1/Parkin Signal Pathway

Cited by 8 publications

References 38 publications

Secreted Protein Acidic and Rich in Cysteine Mediates the Development and Progression of Diabetic Retinopathy

Secreted Protein Acidic and Rich in Cysteine Mediates the Development and Progression of Diabetic Retinopathy

Effective-component compatibility of Bufei Yishen formula III ameliorated COPD by improving airway epithelial cell senescence by promoting mitophagy via the NRF2/PINK1 pathway

High glucose induces apoptosis, glycogen accumulation and suppresses protein synthesis in muscle cells of olive flounder Paralichthys olivaceus

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