The Role of Protein Kinase C and Cyclic AMP in the Ammonia-Induced Shift of the Taurine Uptake/Efflux Balance Towards Efflux in C6 Cells

Zielińska, Magdalena; Zabłocka, Barbara; Dybel, Anna

doi:10.1007/s11064-005-2608-1

Cited by 6 publications

(4 citation statements)

References 41 publications

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“…Hyperammonemia in glial cells results in increased cellular levels of calcium and cAMP [3], [9], [51], [70]. Both calcium and cAMP have been proposed to mediate S100B release [71], [72].…”

Section: Discussionmentioning

confidence: 99%

“…Acute ammonia neurotoxicity can be mediated by an excitotoxic mechanism involving the glutamatergic system, including elevation of extracellular glutamate content, decreased glutamate transporters, NMDA receptor activation and subsequent increases in intracellular calcium concentration [3], [4], [5], [6], [7]. Metabolic effects of ammonia neurotoxicity include changes in reactive oxygen and nitrogen species (ROS/RNS) levels [8], nitric oxide (NO) metabolism [2], cAMP levels [3], [9], mitogen-activated protein kinase (MAPK) pathway [10], cytoskeleton [11] and astrocyte swelling [12]. Moreover, ammonia toxicity also induces increase in tumor necrosis factor α (TNF-α), Interleukin 1β (IL-1β), which can be associated to ROS production and involve protein kinase A (PKA), extracellular signal-regulated kinase (ERK) and nuclear factor-κB (NF-κB) activation [13].…”

Section: Introductionmentioning

confidence: 99%

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Resveratrol Prevents Ammonia Toxicity in Astroglial Cells

et al. 2012

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Ammonia is implicated as a neurotoxin in brain metabolic disorders associated with hyperammonemia. Acute ammonia toxicity can be mediated by an excitotoxic mechanism, oxidative stress and nitric oxide (NO) production. Astrocytes interact with neurons, providing metabolic support and protecting against oxidative stress and excitotoxicity. Astrocytes also convert excess ammonia and glutamate into glutamine via glutamine synthetase (GS). Resveratrol, a polyphenol found in grapes and red wines, exhibits antioxidant and anti-inflammatory properties and modulates glial functions, such as glutamate metabolism. We investigated the effect of resveratrol on the production of reactive oxygen species (ROS), GS activity, S100B secretion, TNF-α, IL-1β and IL-6 levels in astroglial cells exposed to ammonia. Ammonia induced oxidative stress, decreased GS activity and increased cytokines release, probably by a mechanism dependent on protein kinase A (PKA) and extracellular signal-regulated kinase (ERK) pathways. Resveratrol prevented ammonia toxicity by modulating oxidative stress, glial and inflammatory responses. The ERK and nuclear factor-κB (NF-κB) are involved in the protective effect of resveratrol on cytokines proinflammatory release. In contrast, other antioxidants (e.g., ascorbic acid and trolox) were not effective against hyperammonemia. Thus, resveratrol could be used to protect against ammonia-induced neurotoxicity.

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“…Hyperammonemia in glial cells results in increased cellular levels of calcium and cAMP [3], [9], [51], [70]. Both calcium and cAMP have been proposed to mediate S100B release [71], [72].…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Resveratrol Prevents Ammonia Toxicity in Astroglial Cells

et al. 2012

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“…Ammonia elevates intracellular cAMP levels in cultured Müller glia (Faff et al ., 1997), in C6 glioma cells (Zielińska et al ., 2005) and in Dictyostelium (Williams et al ., 1993). In the present study, we found not only that ammonia increases cAMP but also that cAMP promotes apoptosis in the murine microglial cell line BV‐2.…”

Section: Discussionmentioning

confidence: 99%

cAMP mediates ammonia‐induced programmed cell death in the microglial cell line BV‐2

Svoboda

Zierler

Kerschbaum

2007

Eur J of Neuroscience

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Although ammonia is a well-known neuropathogenic factor, the cellular mechanisms of ammonia toxicity are less characterized. Up to now, the main focus of ammonia toxicity has been on astrocytes and neurons. Despite the significance of microglia in neurodegenerative diseases, little is known about their responsiveness to ammonia. In the present study, we found that ammonia triggered mitosis at concentrations between 30 microm and 3.0 mm but apoptosis at concentrations >or= 1.0 mm in the murine microglial cell line BV-2. Most apoptotic cells showed an accumulation of condensed chromatin at the nuclear envelope, blebbing of the plasma membrane, formation of apoptotic bodies and an increase in caspase 3/7 activity. Blockade of caspase 3/7 activity by Ac-DEVD-CHO suppressed ammonia-induced apoptosis. Surprisingly, some BV-2 cells exposed to ammonia displayed clear signs of mitotic catastrophe, a type of cell death occurring during mitosis. In a further series of experiments, we found that cyclic adenosine 3',5'-monophosphate (cAMP) mediated the apoptogenic effects of ammonia, because (i) ammonia dose-dependently elevated the intracellular cAMP level, (ii) blockade of the adenylyl cyclase by SQ-22536 suppressed ammonia-induced apoptosis, (iii) inhibition of phosphodiesterases (PDEs) by the nonselective PDE inhibitor IBMX, or by the PDE4-selective inhibitor rolipram, increased the relative number of apoptotic cells, and (iv) the cAMP analogues 8-bromoadenosine cAMP and Sp-cAMP mimicked the effect of ammonia and triggered apoptosis. Taken together, our results indicate that distinct concentrations of ammonia trigger opposite signalling pathways in microglial cells.

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“…This suggests that the failure of ammonia-induced M€ uller cell swelling was not caused by triggering endogenous glutamate signaling. Another possibility was that ammonia induces the release of taurine from the cells (Faff et al, 1996); ammonia-induced efflux of taurine via the taurine transporter (Zieli nska et al, 2005) might compensate the osmotic gradient across glial membranes. However, the taurine transporter inhibitor, guanidinoethylsulfonate, did not induce osmotic swelling of M€ uller cell bodies in the presence of ammonia (Fig.…”

Section: Ammonia Does Not Induce Acute Swelling Of Retinal Glial and mentioning

confidence: 99%

Synergistic action of hypoosmolarity and glutamine in inducing acute swelling of retinal glial (Müller) cells

Karl

Wurm

Pannicke

et al. 2010

Glia

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High blood ammonia, elevated glutamine, and hyponatremia are pathogenic factors contributing to astrocytic swelling and brain edema in liver failure. We investigated the effects of hypoosmolarity, ammonia, and glutamine on the induction of glial cell swelling in freshly isolated slices of the rat retina. Glutamine, but not ammonia or hypoosmolarity per se, evoked a rapid (within one minute) swelling of retinal glial (Müller) cell bodies under hypoosmotic conditions. Under isoosmotic conditions, glutamine evoked a delayed swelling after 10 min of exposure. The effect of glutamine was concentration-dependent, with half-maximal and maximal effects at ∼ 0.1 and 0.5 mM. Glutamine in hypoosmotic solution induced a dissipation of the mitochondrial membrane potential. The effects on the mitochondrial membrane potential and the glial soma size were reduced by (i) agents which inhibit the transfer of glutamine into mitochondria and its hydrolysis there, (ii) inhibition of the mitochondrial permeability transition, (iii) inhibitors of oxidative-nitrosative stress, and (iv) inhibitors of phospholipase A(2) and cyclooxygenase. Glutamine-induced glial swelling was also prevented by ATP and adenosine, acting at adenosine A(1) receptors. The data suggest that hypoosmolarity accelerates the swelling-inducing effect of glutamine on retinal glial cells, and that swelling induction by glutamine is mediated by inducing oxidative-nitrosative stress, inflammatory lipid mediators, and mitochondrial dysfunction.

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The Role of Protein Kinase C and Cyclic AMP in the Ammonia-Induced Shift of the Taurine Uptake/Efflux Balance Towards Efflux in C6 Cells

Cited by 6 publications

References 41 publications

Resveratrol Prevents Ammonia Toxicity in Astroglial Cells

Resveratrol Prevents Ammonia Toxicity in Astroglial Cells

cAMP mediates ammonia‐induced programmed cell death in the microglial cell line BV‐2

Synergistic action of hypoosmolarity and glutamine in inducing acute swelling of retinal glial (Müller) cells

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