Effect of thimerosal and other sulfhydryl reagents on calcium permeability in thymus lymphocytes

Pintado, Elı́zabeth; Baquero-Leonis, Domingo; Conde, Manuel; Sobrino, Francisco

doi:10.1016/s0006-2952(94)00401-3

Cited by 18 publications

(8 citation statements)

References 27 publications

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“…Ethylmercury can alternatively be detoxi®ed by glutathione, and was reported to bind directly to glutathione S-transferases (Almar and Dierickx 1990), which was shown by the inhibition of the activity of rat GSTs towards 1-chloro-2,4-dinitrobenzene (Dierickx 1985). Although experiments on the impairment of Ca 2+ homeostasis by thimerosal suggest a direct interaction of thimerosal with cellular SH-groups prior to the splitting of the molecule (Pintado et al 1995), preliminary experimental data on GSTT1 inhibition by thimerosal (Westphal et al 2000) are also more in favour of an interaction of GSTT1 with thimerosal and not with ethylmercury occurring from the hydrolysis of the mother compound. Considering this, the association of the GSTM1 negative genotype as well as the combined deletion with GSTT1 and thimerosal allergy might be of functional relevance.…”

Section: Discussionmentioning

confidence: 99%

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Homozygous gene deletions of the glutathione S -transferases M1 and T1 are associated with thimerosal sensitization

Westphal¹,

Schnuch

Schulz³

et al. 2000

International Archives of Occupational and Environmental Health

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Section: Discussionmentioning

confidence: 99%

“…Adverse health eects of thimerosal were attributed to ethylmercury (Almar and Dierickx 1990;Dierickx 1985) and to the induction of oxidative stress (Pintado et al 1995;Bulat et al 1998). Glutathione is able to prevent the elicitation of a thimerosal allergy (Santucci et al 1998).…”

Section: Introductionmentioning

confidence: 99%

Homozygous gene deletions of the glutathione S -transferases M1 and T1 are associated with thimerosal sensitization

Westphal¹,

Schnuch

Schulz³

et al. 2000

International Archives of Occupational and Environmental Health

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“…Unfortunately, beyond their beneficial metabolic effects, long term mitogenic and potentially tumorigenic effects of vanadium compounds must be considered (reviewed in Ref. 60). When applied to lymphocytes at clinically relevant concentrations, vanadium compounds mimic receptormediated activation.…”

Section: Discussionmentioning

confidence: 99%

Vanadate Induces Calcium Signaling, Ca2+ Release-Activated Ca2+ Channel Activation, and Gene Expression in T Lymphocytes and RBL-2H3 Mast Cells Via Thiol Oxidation

Ehring

Kerschbaum

Fanger

et al. 2000

The Journal of Immunology

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Using ratiometric Ca2+ imaging and patch-clamp measurement of Ca2+ channel activity, we investigated Ca2+ signaling induced by vanadium compounds in Jurkat T lymphocytes and rat basophilic leukemia cells. In the presence of external Ca2+, vanadium compounds produced sustained or oscillatory Ca2+ elevations; in nominally Ca2+-free medium, a transient Ca2+ rise was generated. Vanadate-induced Ca2+ signaling was blocked by heparin, a competitive inhibitor of the 1,4,5-inositol trisphosphate (IP3) receptor, suggesting that Ca2+ influx is secondary to depletion of IP3-sensitive Ca2+ stores. In Jurkat T cells, vanadate also activated the Ca2+-dependent transcription factor, NF-AT. Intracellular dialysis with vanadate activated Ca2+ influx through Ca2+ release-activated Ca2+ (CRAC) channels with kinetics comparable to those of dialysis with IP3. Neither phosphatase inhibitors nor nonhydrolyzable nucleotide analogues modified CRAC channel activation. The action of vanadate, but not IP3, was prevented by the thiol-reducing agent DTT. In addition, the activation of CRAC channels by vanadate was mimicked by the thiol-oxidizing agent chloramine T. These results suggest that vanadate enhances Ca2+ signaling via thiol oxidation of a proximal element in the signal transduction cascade.

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“…26,27 Both ROS and thimerosal cause an increase in intracellular calcium resulting in activation of endogenous endonucleases and apoptosis. [44][45][46][47] Glutathione is an anti-oxidant that protects cells from oxidative stress-induced apoptosis. 34 Glutathione depletion is associated with an increased proportion of cells undergoing apoptosis and glutathione decreases apoptosis in fibroblasts.…”

Section: Figurementioning

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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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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Effect of thimerosal and other sulfhydryl reagents on calcium permeability in thymus lymphocytes

Cited by 18 publications

References 27 publications

Homozygous gene deletions of the glutathione S -transferases M1 and T1 are associated with thimerosal sensitization

Homozygous gene deletions of the glutathione S -transferases M1 and T1 are associated with thimerosal sensitization

Vanadate Induces Calcium Signaling, Ca2+ Release-Activated Ca2+ Channel Activation, and Gene Expression in T Lymphocytes and RBL-2H3 Mast Cells Via Thiol Oxidation

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

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