High glucose induced inflammation is inhibited by copper chelation via rescuing mitochondrial fusion protein 2 in retinal pigment epithelial cells

Dhivya, M. Aloysius; Sulochana, K N; Devi, Subramaniam Rajesh Bharathi

doi:10.1016/j.cellsig.2022.110244

Cited by 8 publications

(6 citation statements)

References 37 publications

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“…However, copper nanoparticles and ions induce retinal defects and retinal cell apoptosis via upregulating unfold protein responses and reactive oxygen species [27]. Copper also participates in high glucose-induced inflammation in RPE cells, which can be rescued by copper chelation [28]. The role of copper-induced cell death, namely cuproptosis, has not yet been well studied in nAMD.…”

Section: Discussionmentioning

confidence: 99%

Identification of Cuproptosis-Related circRNA-miRNA-mRNA Network in Laser-Induced Choroidal Neovascularization Models and in Peripheral Blood Mononuclear Cells of Patients with Neovascular Age-Related Macular Degeneration

Zhang,

Wu,

Wang

et al. 2023

Ophthalmic Res

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Introduction: The aims of this study were to investigate the molecular alterations of cuproptosis-related genes and to construct the cuproptosis-related circular RNA (circRNA)-microRNA (miRNA)-mRNA networks in neovascular age-related macular degeneration (nAMD). Methods: The transcriptional profiles of laser-induced choroid neovascularization (CNV) mouse models and nAMD patient samples were obtained from sequencing and from the GEO database (GSE146887), respectively. The expression levels of ten cuproptosis-related genes (FDX1, DLAT, LIAS, DLD, PDHB, MTF1, CDKN2A, GLS, LIPT1, and PDHA1) were extracted and verified in both mouse CNV models and patient peripheral blood mononuclear cells (PBMCs) samples. The cuproptosis-related circRNA-miRNA-mRNA network was further constructed based on miRNet database, the dataset GSE131646 of small RNA expression profile, and the dataset GSE140178 of circRNA expression profile in mouse CNV models. Results: The significant upregulation of Cdkn2a and Mtf1 and the downregulation of other 5 cuproptosis-related genes were verified in the mouse CNV model, but only CDKN2A significantly upregulated in PBMCs of patients with nAMD. Four miRNAs were detected in the intersection between miRNet prediction and sequencing data: miR-129-5p, miR-129-2-3p, miR-182-5p, and miR-615-3p. There were 9 circRNAs at the intersection of hsa-miR-182-5p and hsa-miR-615-3p predictions, one circRNA predicted by hsa-miR-129-5p and GSE140178 (hsa-circASH1L), and one circRNA predicted by hsa-miR-182-5p and hsa-miR-615-3p (hsa-circNPEPPS). Conclusion: This study suggested the repression of cuproptosis in nAMD pathologies and constructed a cuproptosis-related network of 8 cuproptosis-related genes, 4 miRNAs, and 11 circRNAs.

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Section: Discussionmentioning

confidence: 99%

Identification of Cuproptosis-Related circRNA-miRNA-mRNA Network in Laser-Induced Choroidal Neovascularization Models and in Peripheral Blood Mononuclear Cells of Patients with Neovascular Age-Related Macular Degeneration

Zhang,

Wu,

Wang

et al. 2023

Ophthalmic Res

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“…Metabolic changes can facilitate DR and ER stress in DR retinas and can provide metabolism sensors for glucose fluctuations (hypoglycemia and elevated glucose), O-GlcNAcylation, low-density lipoprotein, copper, and advanced glycation end products (AGEs). [184][185][186] All three UPR pathways are activated in the DR process. [187][188][189][190][191][192][193][194] Function of ER stress in BRB breakdown in DR. BRB can be divided into inner and outer components, with the inner BRB being formed by tight junctions between neighboring retinal capillary endothelial cells and the outer barrier by tight junctions between retinal pigment epithelium (RPE) cells.…”

Section: Involvement Of Er Stress In Primary Open-angle Glaucomamentioning

confidence: 99%

“…216 Overexpression of mfn2 to induce mitochondrial merging also contributes to RPE death. 186 Key isomerases like RPE65, LRAT, and RDH5 that convert light-insensitive all-trans-retinyl ester to light-sensitive 11-cis-retinol for continued visual function in RPE decrease under ER stress. 194 The dual function of autophagy in human retinal pericyte survival has been researched.…”

Section: Involvement Of Er Stress In Primary Open-angle Glaucomamentioning

confidence: 99%

Endoplasmic reticulum stress: molecular mechanism and therapeutic targets

Chen,

Shi,

et al. 2023

Sig Transduct Target Ther

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The endoplasmic reticulum (ER) functions as a quality-control organelle for protein homeostasis, or “proteostasis”. The protein quality control systems involve ER-associated degradation, protein chaperons, and autophagy. ER stress is activated when proteostasis is broken with an accumulation of misfolded and unfolded proteins in the ER. ER stress activates an adaptive unfolded protein response to restore proteostasis by initiating protein kinase R-like ER kinase, activating transcription factor 6, and inositol requiring enzyme 1. ER stress is multifaceted, and acts on aspects at the epigenetic level, including transcription and protein processing. Accumulated data indicates its key role in protein homeostasis and other diverse functions involved in various ocular diseases, such as glaucoma, diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, achromatopsia, cataracts, ocular tumors, ocular surface diseases, and myopia. This review summarizes the molecular mechanisms underlying the aforementioned ocular diseases from an ER stress perspective. Drugs (chemicals, neurotrophic factors, and nanoparticles), gene therapy, and stem cell therapy are used to treat ocular diseases by alleviating ER stress. We delineate the advancement of therapy targeting ER stress to provide new treatment strategies for ocular diseases.

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“…[67] Moreover, copper chelator diethylenetriaminepentaacetic acid (DTPA) could restore the decreased acetylcholine-induced relaxation of the aortic rings in diabetic rats. [68] And penicillamine, another copper chelator, are shown to rescue retinal pigment epithelial cells by alleviating mi-tochondria dysfunction, ER stress and inflammation, [69] which are often found in diabetic epithelial cells. [70][71][72]…”

Section: Gdm Patients 8169mentioning

confidence: 99%

Copper and Diabetes: Current Research and Prospect

Chang,

2023

Molecular Nutrition Food Res

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Copper is an essential trace metal for normal cellular functions; a lack of copper is reported to impair the function of important copper‐binding enzymes, while excess copper could lead to cell death. Numerous studies have shown an association between dietary copper consumption or plasma copper levels and the incidence of diabetes/diabetes complications. And experimental studies have revealed multiple signaling pathways that are triggered by copper shortages or copper overload in diabetic conditions. Moreover, studies show that treated with copper chelators improve vascular function, maintain copper homeostasis, inhibit cuproptosis, and reduce cell toxicity, thereby alleviating diabetic neuropathy, retinopathy, nephropathy, and cardiomyopathy. However, the mechanisms reported in these studies are inconsistent or even contradictory. This review summarizes the precise and tight regulation of copper homeostasis processes, and discusses the latest progress in the association of diabetes and dietary copper/plasma copper. Further, the study pays close attention to the therapeutic potential of copper chelators and copper in diabetes and its complications, and hopes to provide new insight for the treatment of diabetes.

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High glucose induced inflammation is inhibited by copper chelation via rescuing mitochondrial fusion protein 2 in retinal pigment epithelial cells

Cited by 8 publications

References 37 publications

Identification of Cuproptosis-Related circRNA-miRNA-mRNA Network in Laser-Induced Choroidal Neovascularization Models and in Peripheral Blood Mononuclear Cells of Patients with Neovascular Age-Related Macular Degeneration

Identification of Cuproptosis-Related circRNA-miRNA-mRNA Network in Laser-Induced Choroidal Neovascularization Models and in Peripheral Blood Mononuclear Cells of Patients with Neovascular Age-Related Macular Degeneration

Endoplasmic reticulum stress: molecular mechanism and therapeutic targets

Copper and Diabetes: Current Research and Prospect

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