Interactions of methylmercury with rat primary astrocyte cultures: inhibition of rubidium and glutamate uptake and induction of swelling

Aschner, Michael; Eberle, Nancy; Miller, Kent D.; Kimelberg, Harold K.

doi:10.1016/0006-8993(90)91290-w

Cited by 74 publications

(36 citation statements)

References 16 publications

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“…Inorganic mercury ions and organic mercurials are known to affect membrane transport by binding to the sulfhydryl group of membrane proteins [1,2] and altering the permeability to inorganic ions [3][4][5][6][7], organic osmolytes [3,8], and water [9][10][11]. Hg 2+ also affects mitochondrial transport [12][13][14][15], cytoplasmic enzymes [2,16,17], and the cytoskeleton [18].…”

Section: Introductionmentioning

confidence: 99%

“…Hg 2+ also affects mitochondrial transport [12][13][14][15], cytoplasmic enzymes [2,16,17], and the cytoskeleton [18]. Hg 2+ -modification of Na + , K + , and Cl -permeability leads to changes in cell volume and loss of the regulatory volume decrease (RVD) [3,7,19,20]. Mercurial inhibition of RVD has been reported for many different cell types including MDCK [6], astrocytes [3,21], and hepatocytes [4,5], although reportedly acting on different pathways in the different cell types.…”

Section: Introductionmentioning

confidence: 99%

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Dynamic Effects of Hg2+-induced Changes in Cell Volume

Heo¹,

Meng²,

Sachs³

et al. 2008

Cell Biochem Biophys

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Using a microfluidic volume sensor, we studied the dynamic effects of Hg 2+ on hypotonic stressinduced volume changes in CHO cells. A hypotonic challenge to control cells caused them to swell but did not evoke a significant regulatory volume decrease (RVD). Treatment with 100 μM HgCl 2 caused a substantial increase in the steady-state volume following osmotic stress. Continuous hypotonic challenge following a single 10-min exposure to HgCl 2 produced a biphasic volume increase with a steady-state volume 100% larger than control cells. Repeated hypotonic challenges to cells exposed once to Hg 2+ resulted in a sequential approach to the same steady-state volume. Stimulation after reaching steady state caused a reduction in peak cell volume. Repeated stimulation was different than continuous stimulation resulting in a more rapid approach to steady state. Substituting extracellular Na + with impermeant NMDG + in the hypotonic solution produced a rapid RVD-like volume decrease and eliminated the Hg 2+ -induced excess swelling. The volume decrease in the presence of Hg 2+ was inhibited by tetraethylammonium and 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid disodium, blockers of K + and Cl -channels, respectively, suggesting that part of the Hg 2+ effect was increasing NaCl influx over KCl efflux. The presence of multiple phases of steadystate volume and their sensitivity to the stimulation history suggests that factors beyond solute fluxes, such as modification of mechanical stress within the cytoskeleton also plays a role in the response to hypotonic stress.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dynamic Effects of Hg2+-induced Changes in Cell Volume

Heo¹,

Meng²,

Sachs³

et al. 2008

Cell Biochem Biophys

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“…MeHg is easily absorbed from the intestine, and transported into the brain across the blood-brain barrier. 1) It has been demonstrated that MeHg neurotoxicity may be modulated by dysfunction of astrocytes such as disturbing ion homeostasis and the uptake of glutamate [a major excitatory transmitter of the central nervous system (CNS)] in cultures, 2,3) since glutamate can induce neuronal cell damage. [4][5][6] Indeed, a recent study revealed that MK-801, an antagonist of N-methyl-D-aspartate receptor, reduced MeHg toxicity, particularly in the cerebral cortex but not in the cerebellum, 7) suggesting the involvement of glutamate in in vivo MeHg neurotoxicity, at least in the cerebral cortex.…”

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confidence: 99%

Acute Cytotoxic Effects of Mercuric Compounds in Cultured Astrocytes Prepared from Cerebral Hemisphere and Cerebellum of Newborn Rats

Adachi

Kunimoto

2005

Biological & Pharmaceutical Bulletin

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“…[3][4][5] Since MeHg neurotoxicity is observed at relatively local regions, 6) we hypothesized that this might reflect brain region-specific susceptibility to mercury compounds in astrocytes. However, regardless of culture conditions, no differences between astrocytes from the cerebral hemisphere and cerebellum were observed not only in susceptibility but also in mercury accumulation for the first few hours after exposure to MeHg or Hg 2ϩ .…”

mentioning

confidence: 99%