X-linked inhibitor of apoptosis (XIAP), known primarily for its caspase inhibitory properties, has recently been shown to interact with and regulate the levels of COMMD1, a protein associated with a form of canine copper toxicosis. Here, we describe a role for XIAP in copper metabolism. We find that XIAP levels are greatly reduced by intracellular copper accumulation in Wilson's disease and other copper toxicosis disorders and in cells cultured under high copper conditions. Elevated copper levels result in a profound, reversible conformational change in XIAP due to the direct binding of copper to XIAP, which accelerates its degradation and significantly decreases its ability to inhibit caspase-3. This results in a lowering of the apoptotic threshold, sensitizing the cell to apoptosis. These data provide an unsuspected link between copper homeostasis and the regulation of cell death through XIAP and may contribute to the pathophysiology of copper toxicosis disorders.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.molcel.2006.01.033 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Discolored urine in sheep and goats: Clinical, etiological, hematobiochemical, sonographic and postmortem findings.
Open Vet J
April 2024
Department of Pathology and Laboratory Diagnosis, College of Veterinary Medicine, Qassim University, Buraidah, Saudi Arabia.
Background: Bloody urine is classified in farm animals as hematuria, hemoglobinuria, and myoglobinuria. In small ruminants, discolored urine is reported due to several etiologies which is sometimes fatal. Of these causes are babesiosis, bacillary hemoglobinuria, copper toxicity, and hypophosphatemia.
View Article and Find Full Text PDFCopper (Cu) metabolism in domestic herbivores as guide to criteria for predicting the Cu nutritional status of wild ruminants in southern Africa.
J S Afr Vet Assoc
March 2024
Department of Production Animal Studies, Faculty of Veterinary Science, University of Pretoria, South Africa.
In southern Africa game farming has become an effective way of using underutilised resources and a valuable method of preserving and increasing wildlife numbers. However, little is known about the mineral requirements of wild animal species or the assessment of the mineral nutritional status of these species. To establish criteria for estimating the copper (Cu) nutritional status of wildlife, current knowledge about Cu metabolism and criteria for domestic animals has been used.
View Article and Find Full Text PDFMallory-Denk bodies and hepatocellular senescence: a causal relationship?
Virchows Arch
April 2024
Diagnostic and Research Institute of Pathology, Diagnostic & Research Center of Molecular Biomedicine, Medical University of Graz, Neue Stiftingtalstrasse 6, A-8010, Graz, Austria.
Mallory-Denk bodies (MDBs) are hepatocellular cytoplasmic inclusions, which occur in certain chronic liver diseases, such as alcohol-related (ASH) and metabolic dysfunction-associated (MASH) steatohepatitis, copper toxicosis, some drug-induced liver disorders, chronic cholangiopathies, and liver tumors. Our study focused on the expression of the senescence markers p21 and p16 in hepatocytes containing MDBs in steatohepatitis, chronic cholangiopathies with fibrosis or cirrhosis, Wilson's disease, and hepatocellular carcinomas. Cytoplasm and nuclei of MDB-containing hepatocytes as well as MDB inclusions, except those associated with carcinoma cells, were strongly p16-positive, p21-positive, as well as p21-negative nuclei in MDB-containing hepatocytes which were observed whereas MDBs were p21-negative.
View Article and Find Full Text PDFTo Eat or Not to Eat?-Food Safety Aspects of Essential Metals in Seafood.
Foods
November 2023
Institute of Plant Protection, Hungarian University of Agriculture and Life Sciences, Georgikon Campus, Deák F. u. 16, 8360 Keszthely, Hungary.
The popularity of seafoods is high due to their superb dietary properties and healthy composition. However, it is crucial to understand whether they adequately contribute to our essential nutritional needs. Small amounts of essential metals are indispensable in the human body to proper physiological functioning; their deficiency can manifest in various sets of symptoms that can only be eliminated with their intake during treatment or nutrition.
View Article and Find Full Text PDFCopper-associated chronic hepatitis in Cavalier King Charles spaniels.
Vet Rec
February 2024
Department of Veterinary Medicine, Queen's Veterinary School Hospital, University of Cambridge, Cambridge, UK.
Background: Copper-associated chronic hepatitis (CuCH) is poorly characterised in Cavalier King Charles spaniels (CKCS).
Methods: Hepatic copper accumulation was qualitatively and quantitatively assessed, and blood samples were used for genetic testing to screen for known CuCH-associated genetic variants.
Results: The study included 13 CKCS with CuCH and eight unaffected controls.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!