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)

Studies were performed to correlate arginine vasopressin (AVP)-induced changes in epithelial ultrastructure with changes in osmotic water permeability in isolated perfused rat terminal inner medullary collecting ducts (tIMCD). The tubules were perfused in three time periods, i.e., a 40-min basal period, a 40-min period with 0.1 nM AVP in the bath, and a 60-min withdrawal period. In each phase, the osmotic water permeability (Pf) was measured, and the perfused tubules were fixed for electron microscopy. AVP caused a four- to eightfold increase in Pf and induced several ultrastructural changes as follows: increased cell height of IMCD cells, expansion of the intercellular spaces, formation of large vacuoles, and increased coated pit density in the apical plasma membrane [from 0.6 +/- 0.2 (n = 6) to 2.9 +/- 0.3 (n = 7) pits/100 microns membrane length]. During AVP withdrawal, Pf decreased toward the basal value in association with partial reversal of the ultrastructural changes including a decrease in coated pit density to 1.0 +/- 0.2 (n = 4). Stimulation with 8-bromoadenosine 3',5'-cyclic monophosphate (8-bromo-cAMP) (0.1 mM) produced similar changes in Pf. Coated pit density increased to 2.1 +/- 0.4 (n = 4) after cAMP stimulation and after cAMP withdrawal decreased to 1.2 +/- 0.2 (n = 6). In contrast to stimulation with AVP, cAMP stimulation did not result in dilated intercellular spaces or formation of large vacuoles. The only ultrastructural feature that directly correlated with the water permeability was the density of coated pits in the apical membrane. Organelles involved in the endocytic pathway were studied with cationized ferritin or albumin-gold in the luminal perfusate. At the end of 40 min basal perfusion or AVP stimulation, luminal tracer was found almost exclusively in large multivesicular bodies (MVB). Tubules perfused with tracer during AVP withdrawal demonstrated rapid tracer accumulation in small vesicles and small MVB within 3-5 min, a time point corresponding to the rapid phase of Pf decrease. Later (30-60 min) the label was mainly confined to large MVB. Occasionally during AVP stimulation or withdrawal, small coated vesicles and smooth vesicles with coated extensions were noted to contain tracer. The data demonstrate AVP-mediated coated pit formation and cellular changes and show very rapid internalization of apical membrane after AVP withdrawal.
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PMID:Vasopressin- and cAMP-induced changes in ultrastructure of isolated perfused inner medullary collecting ducts. 839 44

Transcription of the H ferritin gene in vivo is stimulated by cAMP and repressed by the E1A oncoprotein. We report here the identification of the cis-element in the human promoter responsive to both cAMP- and E1A-mediated signals. This promoter region is included between positions -62 to -45 and binds a approximate 120-kDa transcription factor called Bbf. Bbf forms a complex in vivo with the coactivator molecules p300 and CBP. Recombinant E1A protein reduces the formation of these complexes. In vivo overexpression of p300 in HeLa cells reverses the E1A-mediated inhibition of the ferritin promoter transcription driven by Bbf. These data suggest the existence of a common mechanism for the cAMP activation and the E1A-mediated repression of H ferritin transcription.
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PMID:A common mechanism underlying the E1A repression and the cAMP stimulation of the H ferritin transcription. 925 95

Biochemical and immunochemical investigations were used in order to study the quantitative and qualitative localization of CAMP factor (protein B) in the cell fractions of Streptococcus agalactiae during the logarithmic growth phase. The dynamic quantitative distribution of CAMP factor activity showed that higher concentrations of CAMP factor were found in the cytoplasm than in the cell envelopes. A maximal intracellular accumulation of CAMP factor activity was observed in the late log phase. Immunoblotting analysis using specific anti-CAMP-IgG showed that CAMP factor could be detected in the different cell fractions of S. agalactiae. During the early log phase, CAMP factor was present as a single 25 kD protein band in the cytoplasm; white it was found together with its 26 and 24 kD satellite proteins in the cytoplasmic membrane and the cell wall as well as in all the cell fractions in the mid- and late log phases. Intracellular CAMP factor exhibited the same antigenic and amphiphilic behaviour as the extracellular species. Additionally, a newly discovered amphiphilic protein of approximately 54 kD which exhibited similar antigenicity with the CAMP factor was present in all the cell fractions. Immunoelectron microscopic examinations using ferritin-labelled antibodies revealed that CAMP factor was mainly found in the cytoplasm, whereas it was associated to a minor extent with the cell envelopes. Interestingly, an accumulation of CAMP factor was also localized either at the sites of cross-wall initiation or at the cell surfaces where the cell wall became autolysed.
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PMID:Immunochemical localization of CAMP factor (protein B) in Streptococcus agalactiae. 926 44

We report that the heterotrimeric transcription factor NFY or "CAAT-binding factor" binds the -60 region of the human H ferritin promoter, the B site. DNA binding analysis with specific antibodies demonstrates that NFY/B/C subunits tightly bind this site and that NFY/C subunit is masked in vivo by binding with other protein(s). NFY binds the co-activator p300. Specifically, the NFY/B subunit interacts with the central segment of p300 in vivo and in vitro. cAMP substantially increases the formation of the NFY.p300 complex. Taken together these data provide a general model of cAMP induction of non-CRE-containing promoters and suggest that the NFY-B.p300 complex is located at the 5' end of the promoter and the NFY-B.C. TFIIB on the 3' end toward the transcription start site.
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PMID:The B subunit of the CAAT-binding factor NFY binds the central segment of the Co-activator p300. 1007 48

When the Malpighian tubules (Mt) of the house cricket (Acheta domesticus) are treated with dibutyryl adenosine 3', 5'-cyclic monophosphate (db-cAMP; 1 mM), which causes a doubling in secretion rate, more than 50% of the cell volume is occupied by vesicles within 420 sec of exposure. In view of the fact that the increase in vesiculation occurs concomitantly with stimulated fluid transport, we set out to determine whether the vesicles are formed as a result of fluid-phase endocytosis (pinocytosis) and subsequently used to transport fluid to the lumen as one means of increasing transport rate. We used fluorescent fluid-phase markers (Lucifer Yellow Carbohydrazide [LYCH] and Alexa 488 hydrazide) and an electron dense marker (cationized ferritin) to elucidate the degree of endocytosis that occurred with db-cAMP stimulation. We found that, although some fluid is taken into the cells of the mid-tubule via endocytosis, it does not coincide with the level of vacuolation present in stimulated tubules. The amount of LYCH transported into the primary urine by the db-cAMP-stimulated Mt decreased by 40% as compared to the unstimulated transport, and the rate of transport of LYCH was only 30% of the unstimulated tubules. In summary, our findings do not support the theory that the majority of the vesicles or vacuoles comprise intracellular, endocytotic compartments formed via a basolateral endocytotic pathway. We also found no evidence to support the functioning of vesicles or vacuoles as transcellular "shuttling" mechanisms to move fluid from the basal region to the apical membrane and into the lumen.
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PMID:Fluid-phase endocytosis does not contribute to rapid fluid secretion in the malpighian tubules of the house cricket, Acheta domesticus. 1175 17

Amino acid sequences of ferritin subunits from three orders of insects (Diptera: Drosophila and Aedes; Lepidoptera: Calpodes and Manduca; and Homoptera: Nilaparvata) were obtained from the public database, and analyzed using structural modeling algorithms. Pattern recognition analysis identifies cell attachment, glycosylation, myristoylation, microbody targeting, phosphorylation, cAMP/cGMP dependent, protein kinase C, casein kinase, and tyrosine kinase sites in these subunits. The modeling analyses suggest that the insect heavy-chain homologues are similar to their vertebrate analogues and retain all active sites, including the ferroxidase center. On the contrary, the insect light-chain homologues are different from their vertebrate counterparts, and show none of these features. Five alpha-helices were located in the Dipteran and Lepidopteran, but not in Homopteran ferritin subunits.
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PMID:Molecular modeling of insect ferritins. 1180 75

The phosphate carrier (PiC) catalyses the import of phosphate into mitochondria where it is needed for ATP synthesis. We have analysed the 5'-flanking region of the human PiC gene and found that it has a single transcriptional initiation site and lacks a TATA box. Through deletion analysis of the -1213/-25 nt region, we identified an activation domain (-223/-25) and an inhibition domain (-1017/-814). The most effective promoter activity in transfected HeLa cells corresponded to the region containing putative binding sites for Sp1 (-163/-142; where Sp1 stands for stimulating protein-1) and CREB (-138/-116; where CREB stands for cAMP-response-element-binding protein). These DNA sequences were active in gel-shift assays in the presence of HeLa cell nuclear extracts or recombinant Sp1 and CREB respectively. Forskolin increased PiC promoter activity via the CREB site. Both footprinting and transfection of deletion constructs of the inhibition region (-1017/-814) showed that PiC silencer activity extends over 25 nt (-943/-919), which specifically binds two proteins present in HeLa cell nuclear extracts. These transcription factors were purified by DNA affinity, analysed by MS and identified as p54(nrb)/NonO (nuclear RNA binding protein) and PSF (protein-associated splicing factor). The PiC silencer region cloned in front of the ferritin promoter conferred a strong inhibition to the heterologous promoter. These findings may provide insight into control of PiC gene expression in different cell types and under different growth conditions. To our knowledge, this is the first study to analyse the regulation of the PiC gene expression in any cell.
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PMID:Functional analysis of the promoter of the mitochondrial phosphate carrier human gene: identification of activator and repressor elements and their transcription factors. 1598 30

Ferritin gene expression is complex and is controlled at transcriptional level in response to a variety of stimuli such as hormones, cytokines and cAMP. Iron, hemin and several compounds, chemically different, also activate the transcription of the ferritin gene. Ferritin biosynthesis is mainly regulated at post-transcriptional level by iron regulatory proteins (IRP1 and IRP2). We previously reported that oxalomalate, a competitive inhibitor of aconitase, remarkably decreases the IRP1 RNA-binding activity and induces a significant increase of ferritin expression. Here, we examined in cells cultured in presence of OMA the IRP1 intracellular content, ferritin biosynthesis and the transcriptional efficiency of H-ferritin gene promoter. Our results demonstrate a peculiar role of OMA that rapidly inactivates IRP1 without affecting IRP1 protein content and subsequently activates H-ferritin gene transcription leading to an overall increase of ferritin biosynthesis. We conclude that OMA regulates H-ferritin biosynthesis acting early at the post-transcriptional level and later on at transcriptional level.
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PMID:Induction of H-ferritin synthesis by oxalomalate is regulated at both the transcriptional and post-transcriptional levels. 1682 96

Emerging evidence indicates that aldosterone causes oxidative stress by stimulating proinflammatory/oxidative mediators, including nuclear factor-kappaB, activating protein (AP-1), and c-Jun N-terminal kinase. Thus, in insulin-resistant type 2 diabetes (T2D), oxidative stress generated by hyperglycemia and aldosterone would potentiate the oxidative destruction of tissue and important regulators of glucose metabolism like adiponectin and insulin. Although heme oxygenase (HO)-1 is cytoprotective, its effects on T2D have not been fully characterized. Here we report an enduring antidiabetic effect of the HO inducer, hemin, on Zucker diabetic-fatty rat (ZDF), a model of insulin-resistant T2D. Chronically applied hemin to ZDF reduced and maintained significantly low fasting and postprandial hyperglycemia for 4 months after therapy. The antidiabetic effect was accompanied by enhanced HO activity, catalase, cyclic GMP, bilirubin, ferritin, total antioxidant capacity, and insulin. In contrast, reduced aldosterone alongside markers/mediators of oxidative stress, including 8-isoprostane, c-Jun N-terminal kinase, nuclear factor-kappaB, AP-1, and AP-2 were observed. Interestingly, in hemin-treated ZDF, inhibitory proteins of insulin-signaling, such as glycogen synthase kinase-3 and protein-tyrosine phosphatase-1B were reduced, whereas agents that promote insulin signaling including adiponectin, cAMP, AMP-activated protein kinase, aldolase-B, and glucose transporter-4 (GLUT4), were robustly increased. Correspondingly, hemin improved ip glucose tolerance, reduced insulin intolerance, and lowered insulin resistance (homeostasis model assessment of insulin resistance), and the inability of insulin to enhance GLUT4 was overturned. These results suggest that the suppression of hyperglycemia and aldosterone-induced oxidative stress alongside the potentiation of insulin-sensitizing pathways may account for the 4-month enduring antidiabetic effect. The synergistic interaction between the HO system, aldolase-B, adiponectin, AMP-activated protein kinase, and GLUT4 may be explored for novel strategies against postprandial/fasting hyperglycemia and insulin-resistant T2D.
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PMID:The heme oxygenase system abates hyperglycemia in Zucker diabetic fatty rats by potentiating insulin-sensitizing pathways. 1910 28

Hyperglycemia-induced oxidative stress is a common phenomenon in diabetes. Since oxidative stress depletes adiponectin and insulin levels, we investigated whether an upregulated heme oxygenase (HO) system would attenuate the oxidative destruction of adiponectin/insulin and improve insulin sensitivity and glucose metabolism in streptozotocin (STZ)-induced type 1 diabetes. HO was upregulated with hemin (15 mg/kg ip) or inhibited with chromium mesoporphyrin (CrMP, 4 micromol/kg ip). Administering hemin to STZ-diabetic rats reduced hyperglycemia and improved glucose metabolism, whereas the HO inhibitor CrMP annulled the antidiabetic effects and/or exacerbated fasting/postprandial hyperglycemia. Interestingly, the antidiabetic effects of hemin lasted for 2 mo after termination of therapy and were accompanied by enhanced HO-1 and HO activity of the soleus muscle, along with potentiation of plasma antioxidants like bilirubin, ferritin, and superoxide dismutase, with corresponding elevation of the total antioxidant capacity. Importantly, hemin abated c-Jun NH2-terminal kinase (JNK), a substance known to inhibit insulin biosynthesis, and suppressed markers/mediators of oxidative stress including 8-isoprostane, nuclear-factor (NF)-kappaB, activating protein (AP)-1, and AP-2 of the soleus muscle. Furthermore, hemin therapy significantly attenuated pancreatic histopathological lesions including acinar cell necrosis, interstitial edema, vacuolization, fibrosis, and mononuclear cell infiltration. Correspondingly, hemin increased plasma insulin and potentiated agents implicated in insulin sensitization and insulin signaling such as adiponectin, adenosine monophosphate-activated protein kinase (AMPK), cAMP, cGMP, and glucose transporter (GLUT)4, a protein required for glucose uptake. These were accompanied by improved glucose tolerance [intraperitoneal glucose tolerance text (IPGTT)], decreased insulin intolerance [intraperitoneal insulin tolerance test (IPITT)], and reduced insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR) index], whereas CrMP nullified the hemin-dependent antidiabetic and insulin-sensitizing effects. In conclusion, by concomitantly enhancing insulin and paradoxically potentiating insulin sensitivity, this study unveils a novel, unique, and long-lasting antidiabetic characteristic of upregulating HO with hemin that could be exploited against insulin-resistant and insulin-dependent diabetes.
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PMID:Heme oxygenase system enhances insulin sensitivity and glucose metabolism in streptozotocin-induced diabetes. 1919 Feb 61


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