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)

The production by hepatocytes of hepcidin, a small defensin-like peptide, is modulated in response to anemia, hypoxia, or inflammation. We studied hepcidin as a marker of iron status (serum iron, ferritin, and soluble receptor of transferrin [sTfR], and as a marker of inflammation among 170 prevalent kidney transplantation (KT) patients and 168 prevalent orthotopic heart transplant (OHT) patients. In addition, we assessed the prevalence of anemia and its relation to measurements of hepcidin, sTfR, and high-sensitivity C-reactive protein, using commercially available enzyme-linked immunosorbent assay (ELISA) kits. Prevalence of anemia was 37% in KT patients and 34% in OHT patients according to the World Health Organisation (WHO) definition. Anemic KT patients displayed significantly higher values of serum creatinine, hepcidin, hsCRP, ferritin, and proteinuria associated with greater use of mTOR and significantly lower CSA therapy. The hemoglobin and estimated glomerular filtration rate (eGFR). Upon multiple regression analysis eGFR, ferritin, and hsCRP independently predicted hepcidin levels, explaining 78% of the variation in hepcidin. Anemic OHT patients showed significantly lower GFR, red blood cell (RBC), and hemoglobin values and significantly higher creatinine and NT-proBNP content. Upon multiple regression analysis the predictors of serum hepcidin were eGFR and ferritin, which explained 68% of the variation in hepcidin. The prevalence of anemia is relatively high and not adequately treated (mainly due to reimbursement regulations) among heart and kidney allograft recipients. In conclusion, elevated hepcidin levels in heart and kidney transplant recipients suggest subclinical inflammation and impaired kidney function.
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PMID:Anemia in heart and kidney allograft recipients: is there a role for hepcidin? 2116 77

Iron chelation therapy can improve hematopoiesis in myelodysplastic syndromes. Only few studies showed hematologic improvement with deferoxamine, and the erythroid responses were correlated with good compliance to long-term treatment. Indeed, single-case reports and data from clinical trials testing the efficacy of deferasirox reported hematologic improvements with varying rates of response in different lineages. Overall, about 760 myelodysplastic syndrome (MDS) patients with iron overload receiving deferasirox were included in six different studies, and an increase in hemoglobin level was reported to range from 6 to 44.5%, an increase in platelet count from 13 to 61%, and in neutrophil count from 3 to 76%. In all the published studies, hematologic improvements were not related to serum ferritin or to non-total binding iron changes; indeed, other pathways were indicated as possible pathogenetic mechanisms, such as decreased NF-kB activity, modulation of mTOR signalling, and reduced reactive oxygen species. The aims of this review are to provide all available information relating clinical and hematologic changes after chelation therapy and to discuss potential mechanisms involved in such responses.
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PMID:An increase in hemoglobin, platelets and white blood cells levels by iron chelation as single treatment in multitransfused patients with myelodysplastic syndromes: clinical evidences and possible biological mechanisms. 2574 85

Changes in the two main intracellular degradation systems, the Ubiquitin-Proteasome System and the Autophagy-Lysosome pathway (ALP) are widely discussed as a hallmark of the aging process. To follow the age-related behavior of both degradation systems we examined their impact on ferritin, known to be degradable by both. Ferritin H was analyzed in young and senescent human fibroblasts, revealing a higher steady-state level in the senescent cells. By blocking both proteolytic systems, we confirmed that particularly the ALP plays a crucial role in ferritin H turnover. However, an unexpected increase in lysosomal activity in the senescent cells, suggests a dysregulation in the autophagy pathway. To further investigate the impaired ferritin H turnover, confocal microscopic colocalization studies of ferritin H with lysosomal-associated membrane protein 2a (Lamp2a) and monodansylcadaverine (MDC) were performed and clearly revealed the degradation of ferritin by macroautophagy. By induction of autophagy via inhibition of mTOR using rapamycin an increase of ferritin H turnover was obtained in senescent cells, demonstrating a mTOR dependent reduction of autophagy in senescent human fibroblasts.
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PMID:Reduced autophagy leads to an impaired ferritin turnover in senescent fibroblasts. 2778 94

Dihydroartemisinin (DHA) has been shown to be capable of inhibiting cancer growth, whereas it remains largely elusive that the underlying molecular mechanism of DHA induced acute myeloid leukemia (AML) cell death. In the present study, we examined the effects of DHA on the proliferation and ferroptosis of AML cells as well as to elucidate the underlying molecular mechanisms. We found that DHA strongly inhibited the viability of AML cell lines and arrest cell cycle at G0/G1 phase. Further studies found that DHA effectively induced AML cells ferroptosis, which was iron-dependent and accompanied by mitochondrial dysfunction. Mechanistically, DHA induced autophagy by regulating the activity of AMPK/mTOR/p70S6k signaling pathway, which accelerated the degradation of ferritin, increased the labile iron pool, promoted the accumulation of cellular ROS and eventually led to ferroptotic cell death. Over expression of ISCU (Iron-sulfur cluster assembly enzyme, a mitochondrial protein) significantly attenuated DHA induced ferroptosis by regulating iron metabolism, rescuing the mitochondrial function and increasing the level of GSH. Meanwhile, FTH reconstituted AML cells also exhibited the reduced lipid peroxides content and restored the DHA-induced ferroptosis. In summary, these results provide experimental evidences on the detailed mechanism of DHA-induced ferroptosis and reveal that DHA might represent a promising therapeutic agent to preferentially target AML cells.
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PMID:DHA inhibits proliferation and induces ferroptosis of leukemia cells through autophagy dependent degradation of ferritin. 3055 9

Everolimus (Eve) is an FDA approved drug that inhibits mammalian target of rapamycin (mTOR). It is employed in breast cancer treatment even if its responsiveness is controversial. In an attempt to increase Eve effectiveness, we have developed a novel Eve nanoformulation exploiting H-ferritin nanocages (HEve) to improve its subcellular delivery. We took advantage of the natural tumor targeting of H-Ferritin, which is mediated by the transferrin receptor-1 (TfR1). Breast cancer cells overexpressing TfR-1 were successfully recognized by H-Ferritin, displaying quick nanocage internalization. HEve has been tested and compared to Eve for in vitro efficacy in sensitive and resistant breast cancer cells. Nanoformulated Eve induced remarkable antiproliferative activity in vitro, making even resistant cell lines sensitive to Eve. Moreover, the antiproliferative activity of HEve is fully in accordance with cytotoxicity observed by cell death assay. Furthermore, the significant increase in anticancer efficacy displayed in HEve-treated samples is due to the improved drug accumulation, as demonstrated by UHPLC-MS/MS quantifications. Our findings suggest that optimizing Eve subcellular delivery, thanks to nanoformulation, determines its improved antitumor activity in a panel of Eve-sensitive or resistant breast cancer cell lines.
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PMID:Everolimus Nanoformulation in Biological Nanoparticles Increases Drug Responsiveness in Resistant and Low-Responsive Breast Cancer Cell Lines. 3138 88