Hypoosmotic swelling affects zinc homeostasis in cultured rat astrocytes

Kruczek, Caroline; Görg, Boris; Keitel, Verena; Pirev, Elvis; Kröncke, Klaus‐Dietrich; Schliess, Freimut; Häussinger, Dieter

doi:10.1002/glia.20737

Cited by 61 publications

(54 citation statements)

References 79 publications

(79 reference statements)

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“…Hypoosmotic astrocyte swelling rapidly increases the levels of cytosolic, mitochondrial and nuclear free Zn 2þ in cultured rat astrocytes [20 ]. The increase of [Zn 2þ ] i depends on NMDA receptor activation and nNOS-catalyzed nitric oxide synthesis, but is insensitive to inhibitors of NADPH oxidase [20 ].…”

Section: Zinc Mobilizationmentioning

confidence: 99%

“…Activation and overexpression of Na-K-Cl-cotransporter 1 (NKCC1) are involved in the swelling response [18,19 ]. Activation of NADPH oxidase isoforms in response to hypoosmotic astrocyte swelling or ammonia exposure is the major source of the early ROS formation [12], whereas Ca 2þ /calmodulin-dependent isoforms of nitric oxide synthase are involved in the swelling-induced nitric oxide synthesis [11,20 ].…”

Section: Ammonia and Astrocyte Swelling Induce Oxidative Stressmentioning

confidence: 99%

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Interaction of oxidative stress, astrocyte swelling and cerebral ammonia toxicity

Häussinger

Görg

2010

Current Opinion in Clinical Nutrition and Metabolic Care

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Oxidative/nitrosative stress and a low-grade cerebral edema as key events in the pathogenesis of ammonia toxicity and hepatic encephalopathy may offer potential new strategies for treatment. Ammonia-induced oxidation of RNA and proteins may impair postsynaptic protein synthesis, which is critically involved in learning and memory consolidation. RNA oxidation offers a novel explanation for multiple disturbances of neurotransmitter systems and gene expression and the cognitive deficits observed in hepatic encephalopathy.

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Section: Zinc Mobilizationmentioning

confidence: 99%

Section: Ammonia and Astrocyte Swelling Induce Oxidative Stressmentioning

confidence: 99%

Interaction of oxidative stress, astrocyte swelling and cerebral ammonia toxicity

Häussinger

Görg

2010

Current Opinion in Clinical Nutrition and Metabolic Care

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117

146

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“…A crucial role in MHC-II, EPO, MT, and GS production seems to be played by zinc, a transition metal that is capable of stimulating EPO and MT production [87][88][89][90]. Furthermore, zinc ions have been shown to induce the dimerization of class II MHC molecules, increasing their activity [88][89][90][91].…”

Section: Discussionmentioning

confidence: 99%

Impaired Synthesis of Erythropoietin, Glutamine Synthetase and Metallothionein in the Skin of NOD/SCID/γ c null and Foxn1 nu/nu Mice with Misbalanced Production of MHC Class II Complex

et al. 2009

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Most skin pathologies are characterized by unbalanced synthesis of major histocompatability complex II (MHC-II) proteins. Healthy skin keratinocytes simultaneously produce large amounts of MHC-II and regeneration-supporting proteins, e.g. erythropoietin (EPO), EPO receptor (EPOR), glutamine synthetase (GS) and metallothionein (MT). To investigate the level of regeneration-supporting proteins in the skin during misbalanced production of MHC-II, skin sections from nonobese diabetic/severe combined immunodeficient (NOD/SCID)/gamma (c) (null) and or Foxn1 nu/nu mice which are a priory known to under- and over-express MHC II, respectively, were used. Double immunofluorescence analysis of NOD/SCID/gamma (c) (null) skin sections showed striking decrease in expression of MHC-II, EPO, GS and MT. In Foxn1 nu/nu mouse skin, GS was strongly expressed in epidermis and in hair follicles (HF), which lacked EPO. In nude mouse skin EPO and MHC-II were over-expressed in dermal fibroblasts and they were completely absent from cortex, channel, medulla and keratinocytes surrounding the HF, suggest a role for EPO in health and pathology of hair follicle. The level of expression of EPO and GS in both mutant mice was confirmed by results of Western blot analyses. Strong immunoresponsiveness of EPOR in the hair channels of NOD/SCID/gamma (c) (null) mouse skin suggests increased requirements of skin cells for EPO and possible benefits of exogenous EPO application during disorders of immune system accompanied by loss MHC-II in skin cells.

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“…[15][16][17] Together with this morphological change, the astrocytic functionality, by which cellular signaling mediated by neuro-/glio-transmitters and degradation of glycogen as the main energy reserve in the brain are tightly regulated, is also altered. [18][19][20][21][22] ATP is a cellular energy source and also plays a critical role as a neuro-/glio-transmitter, 28) and thus the functionality of its receptors involved in the cellular signaling might be different between in vitro cultured and in vivo tissue astrocytes. In this study, however, we demonstrated that in vivo tissue astrocytes express constitutively activated P2X7Rs the same as in vitro cultured ones do.…”

Section: Discussionmentioning

confidence: 99%

“…[15][16][17][18] When astrocytes are activated under pathological conditions, they exhibit different functionalities such as neuro-/glio-transmitter clearance systems. [18][19][20][21][22] These findings may imply the possibility that there are differences in the functional expression of P2X7Rs between in vitro cultured and in vivo tissue astrocytes. Brain acute slice cultures are a widely accepted in vitro experimental system that reflects in vivo cell conditions better than in vitro cell culture ones.…”

mentioning

confidence: 99%

Astrocytes, but Not Neurons, Exhibit Constitutive Activation of P2X7 Receptors in Mouse Acute Cortical Slices under Non-stimulated Resting Conditions

Kamatsuka

Fukagawa

Furuta

et al. 2014

Biological & Pharmaceutical Bulletin

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We previously demonstrated that the P2X7 receptor (P2X7R), a purinergic receptor, expressed by mouse cultured cortical astrocytes is constitutively activated without any exogenous stimulus, differing from the case of neurons. It is well known that astrocytic morphology differs between in vitro and in vivo situations, implying different functionalities. Brain acute slices are widely accepted as an in vitro experimental system that reflects in vivo cell conditions better than in vitro cell culture ones. We examined whether astrocytic P2X7Rs exhibited constitutive activation in mouse cortical slices. In acute cortical slices, P2X7R-immunoreactivity was detected in both glial fibrillary acidic protein-immunopositive astrocytes and microtubuleassociated protein 2-immunopositive neurons. Astrocytic, but not neuronal, spontaneous uptake of propidium iodide, an indicator of P2X7R channel/pore activity, was inhibited by representative antagonists of P2X7R, but they had no effect on the uptake by astrocytes in membrane-permeabilized fixed slices. These findings indicate that astrocytes, but not neurons, in acute cortical slices exhibit constitutive activation of P2X7Rs under non-stimulated resting conditions as in the case of cell culture systems.Key words P2X7 receptor; astrocyte; mouse cortical slice; neuron Among purine receptors, in particular, P2X7 receptors (P2X7Rs) have unique characteristics, and are activated by high concentrations (ca. mM) of ATP, resulting in the formation of a non-selective cationic channel/pore, through which large molecules of up to 900 Da can pass. Through activation of P2X7Rs in neurons, cell death is induced via calcium influx, followed by related cellular events, while activation of P2X7Rs expressed by microglia, brain-resident immune cells, causes generation and/or release of reactive oxygen species (ROS) and pro-inflammatory cytokines. These responses help keep the brain environment clean, while under severe pathological conditions, neuronal injury is exacerbated.

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Hypoosmotic swelling affects zinc homeostasis in cultured rat astrocytes

Cited by 61 publications

References 79 publications

Interaction of oxidative stress, astrocyte swelling and cerebral ammonia toxicity

Interaction of oxidative stress, astrocyte swelling and cerebral ammonia toxicity

Impaired Synthesis of Erythropoietin, Glutamine Synthetase and Metallothionein in the Skin of NOD/SCID/γ c null and Foxn1 nu/nu Mice with Misbalanced Production of MHC Class II Complex

Astrocytes, but Not Neurons, Exhibit Constitutive Activation of P2X7 Receptors in Mouse Acute Cortical Slices under Non-stimulated Resting Conditions

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