Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neutrophils undergo rapid morphological changes as well as metabolic perturbations when stimulated with certain phorbol esters. Stimulated cells initially exhibit pronounced projections emanating from the cell bodies, followed by rounding of the cells, reduction in granule number, and the appearance of intracellular vesicles. We show these vesicles to be derived, at least in part, from the plasmalemma. The experimental approach involved labeling stimulated and unstimulated cells with native ferritin and cationized ferritin, along with the cytochemical localization of ecto-5'-nucleotidase. The labeling patterns of the vesicles indicate that these structures are involved in both phorbol ester-stimulated adsorptive and fluid-phase endocytosis. Neutrophils stimulated with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) exhibit two distinct rates of superoxide release in which the second, prolonged level is approximately 50% of the initial rate. All-trans-retinal, which we have recently shown to stimulate O2- release but not granule exocytosis or cell vesiculation, induces a single prolonged rate of maximal O2- release. Neutrophils treated with both all-trans-retinal and TPA exhibit only a single sustained rate of maximal O2- release similar to that observed with all-trans-retinal alone. Moreover, treatment of cells with all-trans-retinal blocks the vesiculation of neutrophils induced by TPA in a dose-dependent manner. This observation provides a possible explanation for the differences in the kinetics of superoxide release.
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PMID:Cell surface dynamics of neutrophils stimulated with phorbol esters or retinoids. 303 27

A discovery that rapid enzymic isomerization of 13-cis-retinoic acid (13-cRA) to all-trans-retinoic acid (t-RA) can be catalysed by purified hepatic glutathione S-transferases (GSTs; EC 2.5.1.18) from rat is now reported. Rates of cis-trans isomerization were determined quantitatively by HPLC. GST-catalysed reactions reached equilibrium rapidly, in marked contrast with uncatalysed or GSH-catalysed isomerizations. The GST-catalysed reaction exhibited substrate saturation kinetics with a Km of approx. 8 microM. The maximal velocity of the reaction and the catalytic efficiency of GSTs were determined. The initial rate of the reaction increased linearly as a function of enzyme concentration. Catalysis by GSTs was independent of the presence of GSH, indicating that GSTs act as GSH-independent isomerases as well as transferases. Incubation with guanidine (7-8 M) or heat-inactivation of GSTs (100 degrees C for 3 min) decreased isomerase activities by approx. 50% and 75% respectively. The same heat treatment did not significantly inhibit isomerization catalysed by GSH and apoferritin, indicating that the observed decrease in isomerase activity by heat inactivation was not primarily due to oxidation of protein thiol groups in the GSTs. The specific activity of GSTs was approx. 23- and 340-fold those of GSH and apoferritin respectively when comparisons were made on the basis of free thiol concentrations, indicating that free thiol in GSTs cannot account for the majority of observed isomerase activities and suggesting that specific conformations of GSTs are important for such activities. Complete inhibition of the reaction by low concentrations of N-ethylmaleimide (10 microM) demonstrated that intact protein thiols are required for the isomerase activities of GSTs.
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PMID:Glutathione S-transferases act as isomerases in isomerization of 13-cis-retinoic acid to all-trans-retinoic acid in vitro. 958 48

A 56-year-old woman with an acute promyelocytic leukemia (APL) developed a severe all-trans-retinoic (ATRA) syndrome on day 17 of treatment. Shortly after, she presented a picture of pancytopenia, hepatosplenomegaly, increased triglycerides, ferritin, and liver enzymes. A bone marrow biopsy showed abundant macrophages and no evidence of leukemia. Tests for secondary hemophagocytic syndrome (HPS) were negative. A diagnosis of HPS was made. Treatment with dexamethasone and high-dose immunoglobulins was unsuccessful. Consolidation chemotherapy with idarubicin and ATRA rapidly reversed the HPS. The HPS in this patient could be related to the release of macrophage-stimulating cytokines by APL cells during ATRA syndrome.
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PMID:Hemophagocytic syndrome associated with retinoic acid syndrome in acute promyelocytic leukemia. 1516 85

Vitamin A deficiency has been widely associated with perturbations of iron homeostasis, a consequence that can be reversed by retinoid supplementation. Despite the numerous studies that demonstrate an interaction between these 2 nutrients, the mechanistic basis for this relation has not been well characterized. Because iron regulatory proteins (IRP) have been established as central regulators of iron homeostasis, we investigated the potential role of IRP in the regulation of iron homeostasis under conditions of vitamin A deficiency and supplementation with all-trans-retinoic acid (atRA). Rats were fed a control diet or a diet deficient in either vitamin A or iron or both micronutrients. Four parallel groups of rats were supplemented with atRA daily (30 micromol/kg body weight) during the final week of this study. As expected, iron-deficient (-Fe) rats exhibited a decrease in hepatic nonheme iron levels and a subsequent increase in IRP RNA-binding activity, resulting in diminished ferritin abundance. Interestingly, atRA supplementation inhibited the increase in IRP RNA-binding activity in -Fe rats to a level that was not significantly (P = 0.139) different from control values, and it partially restored ferritin abundance. This inhibition of IRP RNA-binding activity by atRA supplementation was also associated with a 40% reduction in transferrin receptor abundance. Taken together, these results indicate that IRP represent a mechanistic link between vitamin A and the regulation of iron homeostasis, a key finding toward further understanding this important nutrient-nutrient interaction.
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PMID:Retinoic acid modulates hepatic iron homeostasis in rats by attenuating the RNA-binding activity of iron regulatory proteins. 1802 84