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)

In Parkinson's disease (PD) an elevation of iron with staging of the disease has been observed in the substantia nigra (SN), especially the zona compacta (ZC). The iron is found to be present in glia, active microglia, macrophages, oligodendrocytes, outside the degenerated dopamine neurons and as a mild halo around Lewy bodies and within melanized dopamine neurons of SNZC. Although in control brains iron is absent in melanized dopamine neurons, in PD it is bound to neuromelanin in a fashion similar to the interaction of iron with synthetic dopamine-melanin. The iron in SNZC is thought to induce oxidative stress and thus be associated with the reported decreases of glutathione peroxidase activity, reduced glutathione (GSH), mitochondrial Complex I activity, calcium binding protein and increase of basal lipid peroxidation. An animal (rat) model of PD has been described in which intranigral iron injection induces a relatively specific lesioning of dopamine neurons resulting in behavioural and biochemical Parkinsonism in rats. Support for the neurotoxicity of iron liberated from an endogenous source has come from the 6-hydroxydopamine model of PD. This neurotoxin is thought to owe its toxicity to the liberation of iron from ferritin, which in turn alters the homeostasis of mitochondrial Ca2+ with the subsequent depletion of tissue GSH, resulting in oxidative stress. Pretreatment of rats with intraventricular injection of a relatively selective prototype iron chelator, desferrioxamine (desferal), attenuates the 6-hydroxydopamine lesion of nigrostriatal dopamine. Thus iron can fulfill the role of a neurotoxin. However it remains to be established whether its role in PD is primary or secondary to some other neurotoxic event.
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PMID:The role of iron in senescence of dopaminergic neurons in Parkinson's disease. 829 1

Human breast cancer remains the most common malignancy in the American women. The ultimate cure of this disease relies on a better understanding of the mechanisms underlying the initiation and progression of this disease. The neoplastic transformation of HBEC in vitro represents a successful model for obtaining knowledge on the molecular and biological alterations that may contribute to the tumorigenic mechanisms. We have presented here a current understanding of chemically transformed HBEC in the following aspects: 1. Factors affecting the transformation of HBEC such as genetic predisposition and differentiation status and prior immortalization; 2. New targets for studying the mechanism of cell immortalization such as alterations in telomerase activity and differential expression of cell cycle dependent genes as well as others recently isolated through differential cloning such as H-ferritin, and a calcium binding protein; 3. Epigenetic and genetic mechanisms underlying cell transformation; 4. The association of microsatellite instability in specific loci on chromosomes 11, 13, and 16 with the progression of cell transformation; and 5. The application of microcell mediated chromosome transfer technique as an approach to testing the functional role of specific genes whose dysregulation or loss of function may contribute to the ultimate cell transformation. Further efforts in this cell system will be directed to determine the roles of identified molecular changes as well as the mapping/cloning of tumor suppressor or senescence genes such as those that may reside on chromosomes 11 or 17.
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PMID:Biological and molecular basis of human breast cancer. 972 85

The morphological analysis of breast cancer development indicates this to be a multistep process that progressively evolves from ductal hyperplasia and atypical ductal hyperplasia, which represent the initial stages of neoplastic growth, to carcinoma in situ, invasive carcinoma, and ultimately metastasis, as has been documented for a number of other malignancies. The understanding of the cellular and molecular processes that lead a normal cell to malignancy requires the analysis of pure populations of human breast epithelial cells (HBEC) representing specific stages of neoplastic progression. The neoplastic transformation of HBEC in vitro represents a successful model for obtaining knowledge about the molecular and biological alterations that may contribute to the tumorigenic mechanisms. We present here a current understanding of chemically transformed HBEC in the following aspects: (1) factors affecting the transformation of HBEC such as immortalization; (2) new targets for studying the mechanism of cell immortalization such as alterations in telomerase activity, differential expression of cell cycle-dependent genes, and others recently isolated through differential cloning, such as H-ferritin, and a calcium binding protein; (3) genetic mechanisms underlying cell transformation; and (4) application of the microcell-mediated chromosome transfer technique as an approach to testing the functional role of specific genes whose dysregulation or loss of function may contribute to the ultimate cell transformation. Further efforts in this cell system will be directed to determining the roles of identified molecular changes as well as the mapping/cloning of tumor suppressor or senescence genes.
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PMID:The pathway of neoplastic transformation of human breast epithelial cells. 1112 Dec 27