The divalent metal ion transporter DMT1 is critical for nonheme iron import. We have previously shown that DMT1 is regulated in vitro by ubiquitination that is facilitated by the adaptor proteins Ndfip1 and Ndfip2. Here we report that in Ndfip1(-/-) mice fed a low- iron diet, DMT1 expression and activity in duodenal enterocytes are significant higher than in the wild-type animals. This correlates with an increase in serum iron levels and transferrin saturation. Liver and spleen iron stores were also increased in Ndfip1(-/-) mice fed a normal diet. Counterintuitive to the increase in iron uptake, Ndfip1(-/-) mice fed a low iron diet develop severe microcytic, hypochromic anemia. We demonstrate that this is due to a combination of iron deficiency and inflammatory disease in Ndfip1(-/-) mice, because Ndfip1(-/-)/Rag1(-/-) immunodeficient mice fed a low iron diet did not develop anemia and showed an iron overload phenotype. These data demonstrate that Ndfip1 is a critical mediator of DMT1 regulation in vivo, particularly under iron restricted conditions.
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http://dx.doi.org/10.1182/blood-2010-07-295287 | DOI Listing |
Exp Neurol
May 2024
Institute of Brain Science and Disease, School of Basic Medicine, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, Qingdao University, Qingdao 266021, China. Electronic address:
Increasing evidence has shown that mitochondrial dysfunction and iron accumulation contribute to the pathogenesis of Parkinson's disease (PD). Nedd4 family interacting protein 1 (Ndfip1) is an adaptor protein of the Nedd4 E3 ubiquitin ligases. We have previously reported that Ndfip1 showed a neuroprotective effect in cell models of PD.
View Article and Find Full Text PDFLong-term memory formation requires de novo RNA and protein synthesis. By using the differential display-polymerase chain reaction strategy, we have presently identified the Nedd4 family interacting protein 1 (Ndfip1) cDNA fragment that is differentially expressed between the slow learners and the fast learners from the water maze learning task in rats. Further, the fast learners show decreased Ndfip1 mRNA and protein expression levels than the slow learners.
View Article and Find Full Text PDFHepatology
November 2023
Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China.
Allergol Immunopathol (Madr)
March 2023
Medical College, Yangzhou University, Yangzhou, China;
Nedd4 family interacting protein 1 () was first mentioned in an article in 2000. Since its discovery, related studies have shown that this protein is associated with apoptosis, neuroprotection, substance transport, ubiquitination, and immune regulation. It is noteworthy that the lack of can lead to death in fetal mice.
View Article and Find Full Text PDFJ Alzheimers Dis
November 2022
Department of Psychiatry, Center for Neurobiology and Behavior, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Background: 5XFAD humanized mutant mice and Trem2 knockout (T2KO) mice are two mouse models relevant to the study of Alzheimer's disease (AD)-related pathology.
Objective: To determine hippocampal transcriptomic and polyadenylation site usage alterations caused by genetic mutations engineered in 5XFAD and T2KO mice.
Methods: Employing a publicly available single-nucleus RNA sequencing dataset, we used Seurat and Sierra analytic programs to identify differentially expressed genes (DEGs) and differential transcript usage (DTU), respectively, in hippocampal cell types from each of the two mouse models.
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