Potential role of sirtuin 1 in Müller glial cells in mice choroidal neovascularization

BackgroundAmong different types of sphingolipids produced by human cells, the possible engagement of ceramide species in the pathogenesis of Alzheimer’s disease (AD) has attracted recent attention. While ceramides are primarily generated by de novo synthesis in mammalian cells, only a limited number of bacterial species, produce ceramides, including phosphoglycerol dihydroceramide (PGDHC) that is produced by the key periodontal pathogen Porphyromonas gingivalis. Emerging evidence indicates that virulence factors produced by P. gingivalis, such as lipopolysaccharide and gingipain, may be engaged in the initiation and/or progression of AD. However, the potential role of PGDHC in the pathogenesis of AD remains unknown. Therefore, the aim of this study was to evaluate the influence of PGDHC on hallmark findings in AD.Material and MethodsCHO-7WD10 and SH-SY-5Y cells were exposed to PGDHC and lipopolysaccharide (LPS) isolated from P. gingivalis. Soluble Aβ42 peptide, amyloid precursor protein (APP), phosphorylated tau and senescence-associated secretory phenotype (SASP) factors were quantified using ELISA and Western blot assays. ResultsOur results indicate that P. gingivalis (Pg)-derived PGDHC, but not Pg-LPS, upregulated secretion of soluble Aβ42 peptide and expression of APP in CHO-7WD10 cells. Furthermore, hyperphosphorylation of tau protein was observed in SH-SY-5Y cells in response to PGDHC lipid. In contrast, Pg-LPS had little, or no significant effect on the tau phosphorylation induced in SH-SY-5Y cells. However, both PGDHC and Pg-LPS contributed to the senescence of SH-SY5Y cells as indicated by the production of senescence-associated secretory phenotype (SASP) markers, including beta-galactosidase, cathepsin B (CtsB), and pro-inflammatory cytokines TNF-α, and IL-6. Additionally, PGDHC diminished expression of the senescence-protection marker sirtuin-1 in SH-SY-5Y cells.ConclusionsAltogether, our results indicate that P. gingivalis-derived PGDHC ceramide promotes amyloidogenesis and hyperphosphorylation, as well as the production of SASP factors. Thus, PGDHC may represent a novel class of bacterial-derived virulence factors for AD associated with periodontitis.

Download Full-text

P3.40 Potential role of sirtuin-1 as druggable target in muscular dystrophy: effect of a chronic resveratrol treatment on in vivo and ex vivo pathological signs of dystrophic mdx mouse

Neuromuscular Disorders ◽

10.1016/j.nmd.2010.07.182 ◽

2010 ◽

Vol 20 (9-10) ◽

pp. 653

Author(s):

A. Cozzoli ◽

R.F. Capogrosso ◽

V.T. Sblendorio ◽

S. Gagliardi ◽

V. Longo ◽

...

Keyword(s):

Muscular Dystrophy ◽

Potential Role ◽

Ex Vivo ◽

Sirtuin 1 ◽

Mdx Mouse ◽

Resveratrol Treatment

Download Full-text

Potential role of the glial water channel aquaporin-4 in epilepsy

Neuron Glia Biology ◽

10.1017/s1740925x08000112 ◽

2007 ◽

Vol 3 (4) ◽

pp. 287-297 ◽

Cited By ~ 24

Author(s):

Mike S. Hsu ◽

Darrin J. Lee ◽

Devin K. Binder

Keyword(s):

Synaptic Transmission ◽

Glial Cells ◽

Extracellular Space ◽

Functional Role ◽

Potential Role ◽

Water Channel ◽

Aquaporin 4 ◽

Membrane Channels ◽

Human Epilepsy

AbstractRecent studies have implicated glial cells in novel physiological roles in the CNS, such as modulation of synaptic transmission, so it is possible that glial cells might have a functional role in the hyperexcitability that is characteristic of epilepsy. Indeed, alterations in distinct astrocyte membrane channels, receptors and transporters have all been associated with the epileptic state. This paper focuses on the potential roles of the glial water channel aquaporin-4 (AQP4) in modulating brain excitability and in epilepsy. We review studies of seizure phenotypes, K+ homeostasis and extracellular space physiology of mice that lack AQP4 (AQP4−/− mice) and discuss the human studies demonstrating alterations of AQP4 in specimens of human epilepsy tissue. We conclude with new studies of AQP4 regulation by seizures and discuss its potential role in the development of epilepsy (epileptogenesis). Although many questions remain unanswered, the available data indicate that AQP4 and its molecular partners might represent important new therapeutic targets.

Download Full-text

P4-204: Potential role of the formyl-peptide-receptors and scavenger receptor MARCO in the signal transduction of amyloid beta 1-42 (Aβ42) in glial cells

Alzheimer s & Dementia ◽

10.1016/j.jalz.2009.04.670 ◽

2009 ◽

Vol 5 (4S_Part_16) ◽

pp. P490-P490

Author(s):

Lars-Ove Brandenburg ◽

Maximilian Konrad ◽

Christoph J. Wruck ◽

Thomas Koch ◽

Ralph Lucius ◽

...

Keyword(s):

Signal Transduction ◽

Glial Cells ◽

Amyloid Beta ◽

Potential Role ◽

Scavenger Receptor ◽

Peptide Receptors ◽

Formyl Peptide Receptors ◽

Formyl Peptide

Download Full-text

Jugular Vein Insufficiency and Choroidal Neovascularization in Moderate Myopia: A New Unknown Factor of Additional Risk?

Case Reports in Ophthalmological Medicine ◽

10.1155/2015/960950 ◽

2015 ◽

Vol 2015 ◽

pp. 1-4

Author(s):

Massimiliano Farina ◽

Cristiano Ratti ◽

Eugenio Novelli

Keyword(s):

Choroidal Neovascularization ◽

Potential Role ◽

Color Doppler ◽

Venous Drainage ◽

Choroidal Blood Flow ◽

Additional Risk ◽

Doppler Study ◽

Blood Flow Reduction ◽

Local Reduction

To date, choroidal blood flow reduction in highly myopic eyes appears to be related to the development of choroidal neovascularization secondary to local reduction of arterial flow. Instead, no evidence of choroidal neovascularization was found in subjects with low or moderate myopia. The authors’ aim has been to encourage new studies regarding the potential role of chronic retinal venous congestion in the pathogenesis of choroidal neovascularization. In December 2011, a 54-year-old woman with moderate bilateral myopia had a sudden block upon swallowing while she was eating. Subsequently (January 2013) metamorphopsia in the left eye revealed macular degeneration with choroidal neovascularization. The related echo-color Doppler study of the neck veins, performed in November 2014, showed an atypical left jugular insufficiency associated with homolateral hypertension of the superior ophthalmic veins. This singular case highlights the necessity to further investigate the potential role of chronic alterations of intra- and extracranial venous drainage in the disruption of choroidal flow in myopic patients.

Download Full-text

High glucose treatment promotes extracellular matrix proteome remodeling in Müller glial cells

PeerJ ◽

10.7717/peerj.11316 ◽

2021 ◽

Vol 9 ◽

pp. e11316

Author(s):

Sandra Sagmeister ◽

Juliane Merl-Pham ◽

Agnese Petrera ◽

Cornelia A. Deeg ◽

Stefanie M. Hauck

Keyword(s):

Extracellular Matrix ◽

Glial Cells ◽

High Glucose ◽

Current Knowledge ◽

Explant Culture ◽

Cell Swelling ◽

Short Term ◽

Müller Glial Cells ◽

Glucose Treatment

Background The underlying pathomechanisms in diabetic retinopathy (DR) remain incompletely understood. The aim of this study was to add to the current knowledge about the particular role of retinal Müller glial cells (RMG) in the initial processes of DR. Methods Applying a quantitative proteomic workflow, we investigated changes of primary porcine RMG under short term high glucose treatment as well as glycolysis inhibition treatment. Results We revealed significant changes in RMG proteome primarily in proteins building the extracellular matrix (ECM) indicating fundamental remodeling processes of ECM as novel rapid response to high glucose treatment. Among others, Osteopontin (SPP1) as well as its interacting integrins were significantly downregulated and organotypic retinal explant culture confirmed the selective loss of SPP1 in RMG upon treatment. Since SPP1 in the retina has been described neuroprotective for photoreceptors and functions against experimentally induced cell swelling, it’s rapid loss under diabetic conditions may point to a direct involvement of RMG to the early neurodegenerative processes driving DR. Data are available via ProteomeXchange with identifier PXD015879.

Download Full-text

NEU1 is more abundant in uveitic retina with concomitant desialylation of retinal cells

Glycobiology ◽

10.1093/glycob/cwab014 ◽

2021 ◽

Cited By ~ 1

Author(s):

Lea Lorenz ◽

Barbara Amann ◽

Sieglinde Hirmer ◽

Roxane L Degroote ◽

Stefanie M Hauck ◽

...

Keyword(s):

Autoimmune Disease ◽

Glial Cells ◽

Lectin Binding ◽

Sialic Acids ◽

Binding Assays ◽

Retinal Cells ◽

Müller Glial Cells ◽

Equine Recurrent Uveitis ◽

Spontaneous Animal Model

Abstract Desialylation of cell surface glycoproteins carried out by sialidases affects various immunological processes. However, the role of neuraminidase 1 (NEU1), one of the four mammalian sialidases, in inflammation and autoimmune disease is not completely unraveled to date. In this study, we analyzed the retinal expression of NEU1 in equine recurrent uveitis (ERU), a spontaneous animal model for autoimmune uveitis. Mass spectrometry revealed significantly higher abundance of NEU1 in retinal Müller glial cells (RMG) of ERU-diseased horses compared to healthy controls. Immunohistochemistry uncovered NEU1 expression along the whole Müller cell body in healthy and uveitic states and confirmed higher abundance in inflamed retina. Müller glial cells are the principal macroglial cells of the retina and play a crucial role in uveitis pathogenesis. To determine whether higher expression levels of NEU1 in uveitic RMG correlate with the desialylation of retinal cells, we performed lectin-binding assays with sialic acid-specific lectins. Through these experiments, we could demonstrate a profound loss of both α2-3- and α2-6-linked terminal sialic acids in uveitis. Hence, we hypothesize that the higher abundance of NEU1 in uveitic RMG plays an important role in the pathogenesis of uveitis by desialylation of retinal cells. As RMG become activated in the course of uveitis and actively promote inflammation, we propose that NEU1 might represent a novel activation marker for inflammatory RMG. Our data provide novel insights in the expression and implication of NEU1 in inflammation and autoimmune disease.

Download Full-text