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

Previous studies employing rabbit polyclonal anti-human liver ferritin have shown an absence of L ferritin immunoreactivity in liver and spleen tissue from patients with Niemann-Pick disease type C1 (NPC1). The great majority of NPC cases is caused by defects of the NPC1 gene, and a minority by those of another (NPC2). In this study using polyclonal and monoclonal antibodies we show the deficiency of H and L ferritin isoforms in various NPC tissues, including fetal NPC1, not previously described. In particular, evidence is provided for deficiency in H and L ferritins in tissues, except lung, from a patient with Niemann-Pick disease type C2 (NPC2). The present findings indicate that H and L ferritins are deficient in both NPC types characterized by accumulation of unesterified cholesterol and additional metabolites in the endosomal/lysosomal system. We hypothesize that the lesions in NPC1 and NPC2 block the intracellular utilization not only of cholesterol, but also that of iron for the synthesis of cytosolic ferritin.
 ...
PMID:Deficient ferritin immunoreactivity in tissues from niemann-pick type C patients: extension of findings to fetal tissues, H and L ferritin isoforms, but also one case of the rare Niemann-Pick C2 complementation group. 1092 74

Niemann-Pick C disease (NPC) is a vesicular trafficking disorder primarily caused by mutations in the Npc1 gene and characterized by liver dysfunction and neuropathology. Altered hepatic copper metabolism has recently been reported in NPC disease. Therefore, we aimed to analyze the effects of a copper deficient diet and copper chelation using d-penicillamine on copper homeostasis in the liver of Npc1(-/-) mice of different ages. We examined liver metal ion content by AAS, and copper and iron metabolism gene expression in the liver using qPCR in Npc1(+/+) and Npc1(-/-) mice. We found higher copper and lower iron content in the liver of Npc1(-/-) mice of different ages, compared to controls; these changes in copper and iron content were correlated with increased ceruloplasmin, metallothionein 1, and transferrin receptor gene expression and decreased gene expression of Commd1, ferritin-light chain and ferroportin in the liver of Npc1(-/-) mice of different ages. Npc1(-/-) mice responded to a copper-deficient diet with a decrease in copper content in the liver, bile and heart. These results correlated with a reduction in the hepatic expression of ceruloplasmin and metallothionein 1 during the first week of treatment. d-penicillamine revealed hepatic adaptive response and an improvement in hepatic function in Npc1(-/-) mice without any effect on neurological functions. Our results confirm that the NPC1 protein is required for copper and iron homeostasis. To our knowledge, this is the first report documenting the hepatic adaptive response to low-copper intake in a Npc1(-/-) mouse model.
...
PMID:Hepatic metabolic response to restricted copper intake in a Niemann-Pick C murine model. 2490 80