Ceruloplasmin deletion in myelinating glial cells induces myelin disruption and oxidative stress in the central and peripheral nervous systems

Retinal Müller glial cells (MGs) are among the first to demonstrate metabolic changes during retinal disease and are a potential source of regenerative cells. In response to a harmful stimulus, they can dedifferentiate acquiring neural stem cells properties, proliferate and migrate to the damaged retinal layer and differentiate into lost neurons. However, it is not yet known how this reprogramming process is regulated in mammals. Since glucose and oxygen are important regulatory elements that may help directing stem cell fate, we aimed to study the effect of glucose variations and oxidative stress in Müller cells reprogramming capacity and analyze the participation the histone deacetylase SIRT6, as an epigenetic modulator of this process. We found that the combination of high glucose and oxidative stress induced a decrease in the levels of the marker glutamine synthetase, and an increase in the migration capacity of the cells suggesting that these experimental conditions could induce some degree of dedifferentiation and favor the migration ability. High glucose induced an increase in the levels of the pluripotent factor SOX9 and a decrease in SIRT6 levels accompanied by the increase in the acetylation levels of H3K9. Inhibiting SIRT6 expression by siRNA rendered an increase in SOX9 levels. We also determined SOX9 levels in retinas from mice with a conditional deletion of SIRT6 in the CNS. To further understand the mechanisms that regulate MGs response under metabolic impaired conditions, we evaluated the gene expression profile and performed Gene Ontology enrichment analysis of Müller cells from a murine model of Diabetes. We found several differentially expressed genes and observed that the transcriptomic change involved the enrichment of genes associated with glucose metabolism, cell migration, development and pluripotency. We found that many functional categories affected in cells of diabetic animals were directly related to SIRT6 function. Transcription factors enrichment analysis allowed us to predict several factors, including SOX9, that may be involved in the modulation of the differential expression program observed in diabetic MGs. Our results underline the heterogeneity of Müller cells response and the challenge that the study of metabolic impairment in vivo represents.

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Effects of hyperglycemia and oxidative stress on the glutamate transporters GLAST and system xc − in mouse retinal Müller glial cells

Cell and Tissue Research ◽

10.1007/s00441-008-0742-1 ◽

2009 ◽

Vol 335 (3) ◽

pp. 477-488 ◽

Cited By ~ 41

Author(s):

Barbara Mysona ◽

Ying Dun ◽

Jennifer Duplantier ◽

Vadivel Ganapathy ◽

Sylvia B. Smith

Keyword(s):

Oxidative Stress ◽

Glial Cells ◽

Glutamate Transporters ◽

Müller Glial Cells ◽

And Oxidative Stress

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Protective Effect of Ethosuximide against Glutamate-Induced Cytotoxicity and Oxidative Stress in C6 Glial Cells

10.7176/jstr/7-08-10 ◽

2021 ◽

Keyword(s):

Oxidative Stress ◽

Protective Effect ◽

Glial Cells ◽

And Oxidative Stress

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Toxicity and oxidative stress of acrylonitrile in rat primary glial cells: Preventive effects of N-acetylcysteine

Toxicology Letters ◽

10.1016/j.toxlet.2007.05.001 ◽

2007 ◽

Vol 171 (3) ◽

pp. 111-118 ◽

Cited By ~ 28

Author(s):

A ESMAT ◽

E ELDEMERDASH ◽

H ELMESALLAMY ◽

A ABDELNAIM

Keyword(s):

Oxidative Stress ◽

Glial Cells ◽

Preventive Effects ◽

And Oxidative Stress

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Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1) are localized in the nucleus of retinal Müller glial cells and modulated by cytokines and oxidative stress

PLoS ONE ◽

10.1371/journal.pone.0253915 ◽

2021 ◽

Vol 16 (7) ◽

pp. e0253915

Author(s):

Eun-Jin Lee ◽

Mengmei Zheng ◽

Cheryl Mae Craft ◽

Shinwu Jeong

Keyword(s):

Oxidative Stress ◽

Glial Cells ◽

Molecular Mechanisms ◽

Expression Patterns ◽

Dependent Manner ◽

Tissue Inhibitor Of Metalloproteinases ◽

Tissue Inhibitor ◽

Müller Glial Cells ◽

Tnf Α ◽

And Oxidative Stress

Matrix metalloproteinases (MMPs) are involved in the pathology of numerous inflammatory retinal degenerations, including retinitis pigmentosa (RP). Our previous work revealed that intravitreal injections with tissue inhibitor of metalloproteinases 1 (TIMP-1) reduce the progression of rod cell death and inhibit cone cell remodeling that involves reactive gliosis in retinal Müller glial cells (MGCs) in rodent models. The underlying cellular and molecular mechanisms of how TIMP-1 functions in the retina remain to be resolved; however, MGCs are involved in structural homeostasis, neuronal cell survival and death. In the present study, MMP-9 and TIMP-1 expression patterns were investigated in a human MGC line (MIO-M1) under inflammatory cytokine (IL-1β and TNF-α) and oxidative stress (H2O2) conditions. First, both IL-1β and TNF-α, but not H2O2, have a mild in vitro pro-survival effect on MIO-M1 cells. Treatment with either cytokine results in the imbalanced secretion of MMP-9 and TIMP-1. H2O2 treatment has little effect on their secretion. The investigation of their intracellular expression led to interesting observations. MMP-9 and TIMP-1 are both expressed, not only in the cytoplasm, but also inside the nucleus. None of the treatments alters the MMP-9 intracellular distribution pattern. In contrast to MMP-9, TIMP-1 is detected as speckles. Intracellular TIMP-1 aggregation forms in the cytoplasmic area with IL-1β treatment. With H2O2 treatments, the cell morphology changes from cobbles to spindle shapes and the nuclei become larger with increases in TIMP-1 speckles in an H2O2 dose-dependent manner. Two TIMP-1 cell surface receptors, low density lipoprotein receptor-related protein-1 (LRP-1) and cluster of differentiation 82 (CD82), are expressed within the nucleus of MIO-M1 cells. Overall, these observations suggest that intracellular TIMP-1 is a target of proinflammatory and oxidative insults in the MGCs. Given the importance of the roles for MGCs in the retina, the functional implication of nuclear TIMP-1 and MMP-9 in MGCs is discussed.

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1638: Erectile Dysfunction and Oxidative Stress-Media Ted Cavernosal Cell Death in Spontaneously Hypertensive Rats

The Journal of Urology ◽

10.1016/s0022-5347(18)38846-3 ◽

2004 ◽

Vol 171 (4S) ◽

pp. 433-433

Author(s):

Steven Kuntz ◽

Steven White ◽

Michael Alba ◽

Mahadevan Rajasekaran

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Erectile Dysfunction ◽

Spontaneously Hypertensive Rats ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

And Oxidative Stress

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Association between calcitriol and paricalcitol with oxidative stress in patients with hemodialysis

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000641 ◽

2020 ◽

pp. 1-8

Author(s):

Hasan Haci Yeter ◽

Berfu Korucu ◽

Elif Burcu Bali ◽

Ulver Derici

Keyword(s):

Oxidative Stress ◽

Vitamin D ◽

Antioxidant Status ◽

Total Antioxidant Status ◽

Stress Index ◽

Total Oxidant Status ◽

Vitamin D Analog ◽

Total Antioxidant ◽

Oxidant Status ◽

And Oxidative Stress

Abstract. Background: The pathophysiological basis of chronic kidney disease and its complications, including cardiovascular disease, are associated with chronic inflammation and oxidative stress. We investigated the effects of active vitamin D (calcitriol) and synthetic vitamin D analog (paricalcitol) on oxidative stress in hemodialysis patients. Methods: This cross-sectional study was composed of 83 patients with a minimum hemodialysis vintage of one year. Patients with a history of any infection, malignancy, and chronic inflammatory disease were excluded. Oxidative markers (total oxidant and antioxidant status) and inflammation markers (C-reactive protein and interleukin-6) were analyzed. Results: A total of 47% (39/83) patients were using active or analog vitamin D. Total antioxidant status was significantly higher in patients with using active or analog vitamin D than those who did not use (p = 0.006). Whereas, total oxidant status and oxidative stress index were significantly higher in patients with not using vitamin D when compared with the patients who were using vitamin D preparation (p = 0.005 and p = 0.004, respectively). On the other hand, total antioxidant status, total oxidant status, and oxidative stress index were similar between patients who used active vitamin D or vitamin D analog (p = 0.6; p = 0.4 and p = 0.7, respectively). Conclusion: The use of active or selective vitamin D analog in these patients decreases total oxidant status and increases total antioxidant status. Also, paricalcitol is as effective as calcitriol in decreasing total oxidant status and increasing total antioxidant status in patients with chronic kidney disease.

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