Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mediators of lymphocyte infiltration in inflammatory thyroid disease have yet to be identified. Here we examine the ability of IL-1beta to enhance the production of chemoattractants by human thyrocytes. Primary cultures, when treated with the cytokine, release T lymphocyte chemotactic activity. The effect of IL-1beta is time dependent, and the chemoattraction activity can be partially attenuated by the addition of either anti-IL-16 or anti-regulated upon activation, normal T cell expressed, and secreted (RANTES) neutralizing antibodies. IL-16 is a CD4(+)-specific ligand, and RANTES is a C-C type chemokine that targets monocytes and lymphocytes. These chemoattractants could be detected by specific ELISAs in conditioned medium from IL-1beta treated thyrocytes. Northern analysis revealed that thyrocytes express high constitutive levels of IL-16 mRNA, which were invariant with regard to IL-1beta (10 ng/ml) or glucocorticoid treatment. RANTES mRNA was not detected in control cultures but was strongly induced by the cytokine. IL-16 but not RANTES expression was dependent on the activity of caspase-3. Pro-IL-16 protein could be detected in homogenates of thyroid tissue from patients with multinodular goiter and Graves' disease. Thus, human thyrocytes, through the expression of chemoattractants, may participate in the recruitment of lymphocytes to the thyroid in inflammatory states.
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PMID:Cytokine-induced lymphocyte chemoattraction from cultured human thyrocytes: evidence for interleukin-16 and regulated upon activation, normal T cell expressed, and secreted expression. 1281 May 40

Oxidative stress and mitochondrial dysfunction are common features in patients with sepsis and organ failure. Within mitochondria, superoxide is converted into hydrogen peroxide by MnSOD (manganese-containing superoxide dismutase), which is then detoxified by either the mGSH (mitochondrial glutathione) system, using the enzymes mGPx-1 (mitochondrial glutathione peroxidase-1), GRD (glutathione reductase) and mGSH, or the TRX-2 (thioredoxin-2) system, which uses the enzymes PRX-3 (peroxiredoxin-3) and TRX-2R (thioredoxin reductase-2) and TRX-2. In the present paper we investigated the relative contribution of these two systems, using selective inhibitors, in relation to mitochondrial dysfunction in endothelial cells cultured with LPS (lipopolysaccharide) and PepG (peptidoglycan). Specific inhibition of both the TRX-2 and mGSH systems increased the intracellular total radical production (P<0.05) and reduced mitochondrial membrane potentials (P<0.05). Inhibition of the TRX-2 system, but not mGSH, resulted in lower ATP production (P<0.001) with high metabolic activity (P<0.001), low oxygen consumption (P<0.001) and increased lactate production (P<0.001) and caspase 3/7 activation (P<0.05). Collectively these results show that the TRX-2 system appears to have a more important role in preventing mitochondrial dysfunction than the mGSH system in endothelial cells under conditions that mimic a septic insult.
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PMID:Mitochondrial protection by the thioredoxin-2 and glutathione systems in an in vitro endothelial model of sepsis. 2135 52

Radioiodide ((131)I) is routinely used for the treatment of toxic adenoma, Graves' disease, and for ablation of thyroid remnant after thyroidectomy in patients with thyroid cancer. The toxic effects of ionizing radiations on living cells can be mediated by a necrotic and/or apoptotic process. The involvement of apoptosis in radiation-induced cell death in the thyrocytes has been questioned. The knowledge of the mechanisms that underlie the thyrocyte death in response to radiations can help to achieve a successful treatment with the lowest (131)I dose. We developed a method to study the effects of (131)I in human thyroid tissue in culture, by which we demonstrated that (131)I induces thyroid cell apoptosis. Human thyroid tissues of about 1 mm(3) were cultured in vitro and cell viability was determined up to 3 weeks by the MTT assay. Radioiodide added to the culture medium was actively taken up by the tissues. The occurrence of apoptosis in the thyrocytes was assessed by measuring the production of a caspase-cleavage fragment of cytokeratin 18 (M30) by an enzyme-linked immunoassay. Neither variation of cell number nor spontaneous apoptosis was revealed after 1 week of culture. (131)I added to the culture medium induced a dose-dependent and a time-dependent generation of M30 fragment. The apoptotic process was confirmed by the generation of caspase-3 and PARP cleavage products. These results demonstrate that (131)I induces apoptosis in human thyrocytes. Human thyroid tissue cultures may be useful to investigate the cell death pathways induced by (131)I.
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PMID:Radioiodide induces apoptosis in human thyroid tissue in culture. 2399 Feb 67