Manganese suppresses ATP-dependent intercellular calcium waves in astrocyte networks through alteration of mitochondrial and endoplasmic reticulum calcium dynamics

Tjalkens, Ronald B.; Zoran, Mark J.; Mohl, Brianne; Barhoumi, Roula

doi:10.1016/j.brainres.2006.07.053

Cited by 55 publications

(37 citation statements)

References 38 publications

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“…Confluent astrocytes were sub-cultured onto 4-well poly-D-lysine-coated chambered glass slides (Nalgene-Nunc, Thermo Fisher Scientific, Waltham, MA) and allowed to grow to approximately 75% confluence. In our laboratory, cultures consistently yield>98% astrocytes as determined by immunofluorescence staining for glial fibrillary acidic protein [19].…”

Section: Methodsmentioning

confidence: 84%

Dopaminergic Neurotoxicants Cause Biphasic Inhibition of Purinergic Calcium Signaling in Astrocytes

et al. 2014

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Dopaminergic nuclei in the basal ganglia are highly sensitive to damage from oxidative stress, inflammation, and environmental neurotoxins. Disruption of adenosine triphosphate (ATP)-dependent calcium (Ca2+) transients in astrocytes may represent an important target of such stressors that contributes to neuronal injury by disrupting critical Ca2+-dependent trophic functions. We therefore postulated that plasma membrane cation channels might be a common site of inhibition by structurally distinct cationic neurotoxicants that could modulate ATP-induced Ca2+ signals in astrocytes. To test this, we examined the capacity of two dopaminergic neurotoxicants to alter ATP-dependent Ca2+ waves and transients in primary murine striatal astrocytes: MPP+, the active metabolite of 1-methyl 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and 6-hydroxydopamine (6-OHDA). Both compounds acutely decreased ATP-induced Ca2+ transients and waves in astrocytes and blocked OAG-induced Ca2+ influx at micromolar concentrations, suggesting the transient receptor potential channel, TRPC3, as an acute target. MPP+ inhibited 1-oleoyl-2-acetyl-sn-glycerol (OAG)-induced Ca2+ transients similarly to the TRPC3 antagonist, pyrazole-3, whereas 6-OHDA only partly suppressed OAG-induced transients. RNAi directed against TRPC3 inhibited the ATP-induced transient as well as entry of extracellular Ca2+, which was augmented by MPP+. Whole-cell patch clamp experiments in primary astrocytes and TRPC3-overexpressing cells demonstrated that acute application of MPP+ completely blocked OAG-induced TRPC3 currents, whereas 6-OHDA only partially inhibited OAG currents. These findings indicate that MPP+ and 6-OHDA inhibit ATP-induced Ca2+ signals in astrocytes in part by interfering with purinergic receptor mediated activation of TRPC3, suggesting a novel pathway in glia that could contribute to neurotoxic injury.

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Section: Methodsmentioning

confidence: 84%

Dopaminergic Neurotoxicants Cause Biphasic Inhibition of Purinergic Calcium Signaling in Astrocytes

et al. 2014

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“…The function of this messenger was deduced by monitoring the dynamic and in time changes of the concentration and distribution of Ca 2+ [4][5][6]. Currently, the numbers of commercial Ca 2+ -sensitive fluorescent probes are limited and contain defects.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and application of intercellular Ca2+-sensitive fluorescent probe based on quantum dots

Xia¹,

Yu²,

Liao³

et al. 2013

Journal of Inorganic Biochemistry

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“…They found that Mn 2+ could inhibit total Ca 2+ -ATPase in rhesus monkey brain after exposed to Mn 2+ . In addition, Mn could alter ATP-dependent intracellular Ca 2+ dynamics in astrocytes and suppress Ca 2+ wave activity [32]. The consequence of this study showed that the efficiency of Ca pumps decreased and Ca 2+ overload because of overexcitation of NMDAR, which can lead to cytotoxicity and excitotoxicity [15].…”

Section: Discussionmentioning

confidence: 97%

Excitotoxicity in Rat’s Brain Induced by Exposure of Manganese and Neuroprotective Effects of Pinacidil and Nimodipine

Deng

et al. 2009

Biol Trace Elem Res

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Manganese (Mn) is an essential trace element for humans. However, manganism would be caused by excessive Mn. The mechanisms underlying excitotoxicity induced by manganism are poorly understood. As it is known to us, glutamate (Glu) is the most prevalent excitatory neurotransmitter. To determine the possible role of dysfunction of Glu transportation and metabolism in Mn-induced excitotoxicity, the rats were ip injected with different dose of MnCl(2) (0, 50, 100, and 200 micromol/kg), the levels of Mn and activities of GS, PAG, Na(+)-K(+)-ATPase, and Ca(2+)-ATPase in striatum were investigated. In addition, effect of 20.38 micromol/kg pinacidil (K(+) channel opener) or 2.4 micromol/kg nimodipine (Ca(2+) channel blocker) were studied at 200 micromol/kg MnCl(2). With dose-dependent inhibition of GS, Na(+)-K(+)-ATPase, and Ca(2+)-ATPase activities, increase of Mn levels and PAG activity were observed. Further investigation indicated that pre-treatment of pinacidil or nimodipine reversed toxic effect of MnCl(2) significantly. These results suggested that MnCl(2) could induce dysfunction of Glu transportation and metabolism by augmenting the excitotoxicity dose-dependently; pinacidil and nimodipine might antagonize manganese neurotoxicity.

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Manganese suppresses ATP-dependent intercellular calcium waves in astrocyte networks through alteration of mitochondrial and endoplasmic reticulum calcium dynamics

Cited by 55 publications

References 38 publications

Dopaminergic Neurotoxicants Cause Biphasic Inhibition of Purinergic Calcium Signaling in Astrocytes

Dopaminergic Neurotoxicants Cause Biphasic Inhibition of Purinergic Calcium Signaling in Astrocytes

Synthesis and application of intercellular Ca2+-sensitive fluorescent probe based on quantum dots

Excitotoxicity in Rat’s Brain Induced by Exposure of Manganese and Neuroprotective Effects of Pinacidil and Nimodipine

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