Thimerosal A versatile sulfhydryl reagent, calcium mobilizer, and cell function-modulating agent

Elferink, J. G. R.

doi:10.1016/s0306-3623(98)00258-4

Cited by 84 publications

(57 citation statements)

References 29 publications

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“…[13][14][15][16][17][18][19][20] Thimerosal, a sulfhydryl reagent, calcium mobilizer, and cell function modulator, is composed of two moieties, the thiosalicylic acid and mercury linked to sulfur. 22 Therefore, we examined the effects of thimerosal on apoptosis in T cells.…”

Section: Discussionmentioning

confidence: 99%

“…22 In order to discriminate the effect of ethylemercury from thiosalicylic acid in thiomerosal, cells (1 × 10 6 cells/ml) were incubated in the presence or absence of 0.5 M, 1.0 M, 2.5 M, 5.0 M Figure 1 Effect of thimerosal on apoptosis in Jurkat T cells. Cells were exposed to various concentrations of thimerosal and apoptosis was measured by TUNEL assay.…”

Section: Thimerosal-induced Apoptosis Is Not Due To Thiosalicylic Acidmentioning

confidence: 99%

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Biochemical and molecular basis of thimerosal-induced apoptosis in T cells: a major role of mitochondrial pathway

et al. 2002

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The major source of thimerosal (ethyl mercury thiosalicylate) . Thimerosal and not thiosalcylic acid (nonmercury component of thimerosal), in a concentration-dependent manner, induced apoptosis in T cells as determined by TUNEL and propidium iodide assays, suggesting a role of mercury in T cell apoptosis. Apoptosis was associated with depolarization of mitochondrial membrane, release of cytochrome c and apoptosis inducing factor (AIF) from the mitochondria, and activation of caspase-9 and caspase-3, but not of caspase-8. In addition, thimerosal in a concentrationdependent manner inhibited the expression of XIAP, cIAP-1 but did not influence cIAP-2 expression. Furthermore, thimerosal enhanced intracellular reactive oxygen species and reduced intracellular glutathione (GSH). Finally, exogenous glutathione protected T cells from thimerosal-induced apoptosis by upregulation of XIAP and cIAP1 and by inhibiting activation of both caspase-9 and caspase-3. These data suggest that thimerosal induces apoptosis in T cells via mitochondrial pathway by inducing oxidative stress and depletion of GSH.

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Section: Discussionmentioning

confidence: 99%

Section: Thimerosal-induced Apoptosis Is Not Due To Thiosalicylic Acidmentioning

confidence: 99%

Biochemical and molecular basis of thimerosal-induced apoptosis in T cells: a major role of mitochondrial pathway

et al. 2002

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“…Thimerosal is a Ca 2 þ -mobilizing agent, capable of releasing Ca 2 þ from intracellular stores and increasing Ca 2 þ entry. 61 Despite its short half-life compared to inorganic mercury, it undergoes preferential accumulation in the CNS, affecting the microglia and producing strain-dependent neurotoxic effects in rodents. 62,63 This strain dependency, in conjunction with the present data, suggests that thimerosal could contribute to produce an unbalanced Ca 2 þ homeostasis in genetically vulnerable individuals.…”

Section: à1688mentioning

confidence: 99%

Altered calcium homeostasis in autism-spectrum disorders: evidence from biochemical and genetic studies of the mitochondrial aspartate/glutamate carrier AGC1

et al. 2008

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Autism is a severe developmental disorder, whose pathogenetic underpinnings are still largely unknown. Temporocortical gray matter from six matched patient-control pairs was used to perform post-mortem biochemical and genetic studies of the mitochondrial aspartate/glutamate carrier (AGC), which participates in the aspartate/malate reduced nicotinamide adenine dinucleotide shuttle and is physiologically activated by calcium (Ca(2+)). AGC transport rates were significantly higher in tissue homogenates from all six patients, including those with no history of seizures and with normal electroencephalograms prior to death. This increase was consistently blunted by the Ca(2+) chelator ethylene glycol tetraacetic acid; neocortical Ca(2+) levels were significantly higher in all six patients; no difference in AGC transport rates was found in isolated mitochondria from patients and controls following removal of the Ca(2+)-containing postmitochondrial supernatant. Expression of AGC1, the predominant AGC isoform in brain, and cytochrome c oxidase activity were both increased in autistic patients, indicating an activation of mitochondrial metabolism. Furthermore, oxidized mitochondrial proteins were markedly increased in four of the six patients. Variants of the AGC1-encoding SLC25A12 gene were neither correlated with AGC activation nor associated with autism-spectrum disorders in 309 simplex and 17 multiplex families, whereas some unaffected siblings may carry a protective gene variant. Therefore, excessive Ca(2+) levels are responsible for boosting AGC activity, mitochondrial metabolism and, to a more variable degree, oxidative stress in autistic brains. AGC and altered Ca(2+) homeostasis play a key interactive role in the cascade of signaling events leading to autism: their modulation could provide new preventive and therapeutic strategies. Molecular Psychiatry (2010) 15, 38-52; doi: 10.1038/mp.2008.63; published online 8 July 200

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“…Namely, the extent of activation of IP 3 Rs by thimerosal -a widely used IP 3 R activator ( [30,32]; for review see eg. [8] [21]). Taken together, these results suggest that the main effect of Trisk 32 overexpression is not the alteration of the functionality of SOCE.…”

Section: Discussionmentioning

confidence: 99%

Trisk 32 regulates IP3 receptors in rat skeletal myoblasts

Oláh

Fodor

Oddoux

et al. 2011

Pflugers Arch - Eur J Physiol

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To date four isoforms of triadins have been identified in rat skeletal muscle. While the function of the 95 kDa isoform in excitation-contraction coupling has been studied in detail, the role of the 32 kDa isoform (Trisk 32) remains elusive. Here Trisk 32 overexpression was carried out by stable transfection in L6.G8 myoblasts. Co-localization of Trisk 32 and IP 3 receptors (IP 3 R) was demonstrated by immunocytochemistry and their association was shown by coimmunoprecipitation. Functional effects of Trisk 32 on IP 3 -mediated Ca 2+ release were assessed by measuring changes in [Ca 2+ ] i following the stimulation by bradykinin or vasopressin. The amplitude of the Ca 2+ transients evoked by 20 µM bradykinin was significantly higher in Trisk 32-overexpressing (p<0.01; 426±84 nM, n=27) as compared to control cells (76±12 nM, n=23). The difference remained significant (p<0.02; 217±41 nM, n=21 and 97±29 nM, n=31, respectively) in the absence of extracellular Ca 2+ . Similar observations were made when 0.1 µM vasopressin was used to initiate Ca 2+ release. Possible involvement of the ryanodine receptors (RyR) in these processes was excluded, after functional and biochemical experiments. Furthermore, Trisk 32 overexpression had no effect on store-operated Ca 2+ -entry, despite a decrease in the expression of STIM1. These results suggest that neither the increased activity of RyR, nor the amplification of SOCE are responsible for the differences observed in bradykinin-or vasopressin-evoked Ca 2+ transients, rather, they were due to the enhanced activity of IP 3 R. Thus Trisk 32 not only colocalizes with, but directly contributes to the regulation of Ca 2+ release via IP 3 R.

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Thimerosal A versatile sulfhydryl reagent, calcium mobilizer, and cell function-modulating agent

Cited by 84 publications

References 29 publications

Biochemical and molecular basis of thimerosal-induced apoptosis in T cells: a major role of mitochondrial pathway

Biochemical and molecular basis of thimerosal-induced apoptosis in T cells: a major role of mitochondrial pathway

Altered calcium homeostasis in autism-spectrum disorders: evidence from biochemical and genetic studies of the mitochondrial aspartate/glutamate carrier AGC1

Trisk 32 regulates IP3 receptors in rat skeletal myoblasts

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