Single allele Lmbrd1 knockout results in cardiac hypertrophy

Tseng, Linda Tzu-Ling; Lin, Chieh-Liang; Pan, Kuei-Hsiang; Tzen, Kai-Yuan; Su, Meiying; Tsai, Chia Ti; Li, Yi-Han; Li, Pai‐Chi; Chiang, Fu‐Tien; Chang, Shih‐Chieh; Chang, Shan‐Chwen

doi:10.1016/j.jfma.2017.05.002

Cited by 4 publications

(3 citation statements)

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“…Interestingly, other compounds that are strongly linked with vitamin B12 deficiency-MMA have been recently identified as oncometabolites. MMA is a metabolite of methylmalonyl coenzyme A, and its increased levels result from impaired conversion to succinyl coenzyme A in a vitamin B12dependent manner [180]. A study published in 2020 by Gomes et al revealed that MMA levels increase in the serum of older individuals and may have a function as a mediator of tumor progression.…”

Section: Long-distance Consequences Of Vitamin B12 Deficiencymentioning

confidence: 99%

Vitamin B12 Metabolism: A Network of Multi-Protein Mediated Processes

Mucha,

Kus,

Cysewski

et al. 2024

Preprint

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The water-soluble vitamin - vitamin B12, also known as cobalamin, plays a crucial role in cellular metabolism, particularly in DNA synthesis, methylation, and mitochondrial functionality. Its de-ficiency can lead to hematological and neurological disorders, however the manifestation of these clinical outcomes is relatively late. It leads to difficulties in its early diagnosis, often resulting in the development of hidden subclinical cobalamin deficiency. Prolonged lack of vitamin B12 con-dition may have severe consequences including increased morbidity to neurological and cardio-vascular diseases. Beyond inadequate dietary intake, vitamin B12 deficiency might be caused by insufficient bioavailability, blood transport disruptions, or impaired cellular uptake and metabo-lism. Despite nearly 70 years of knowledge since its isolation and characterization, there are still gaps in understanding its metabolic pathways. Thus, this review aims to gather current knowledge about the crucial proteins necessary to efficiently process vitamin B12 in humans, presenting it as a multi-protein mediated network. Based on these findings, we also highlight new potential methods for supporting the evaluation of the risk of epidemiological consequences of vitamin B12 deficiency or clinical warnings of increased risk of vitamin B12 deficiency based on already testing targeting specific moonlighting proteins engaged in vitamin B12 metabolic path-ways.

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Section: Long-distance Consequences Of Vitamin B12 Deficiencymentioning

confidence: 99%

Vitamin B12 Metabolism: A Network of Multi-Protein Mediated Processes

Mucha,

Kus,

Cysewski

et al. 2024

Preprint

View full text Add to dashboard Cite

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“…Generation of Lmbrd1 +/− mice has been described previously [8]. In brief, Lmbrd1 +/− mice in the background of C57BL/6J were generated by using Cre-LoxP system that allowed deletion of the exon 6 and 7 of the Lmbrd1 gene.…”

Section: Cultured Mouse Embryo Fibroblasts (Mefs)mentioning

confidence: 99%

“…In addition, Lmbrd1 heterozygous knockout causes cardiac hypertrophy in mice due to a significant increase in myocardial glucose uptake. The increase of glucose uptake is a consequence of constitutive activation of IR signaling pathway resulting from the retention of IR on the plasma membrane [8]. Furthermore, LMBD1 function is essential for the expression of fibroblast growth factor 8 to provide intact gastrulation and mesoderm formation during mouse embryogenesis [9].…”

Section: Introductionmentioning

confidence: 99%

LMBD1 protein participates in cell mitosis by regulating microtubule assembly

Sun

Chang

Wang

et al. 2021

Biochemical Journal

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LMBD1 was previously demonstrated to regulate the endocytosis of insulin receptor on cell surface and to mediate the export of cobalamin from the lysosomes to cytosol, but little is known about its function in mitosis. In this study, interactome analysis data indicate that LMBD1 is involved in cytoskeleton regulation. Both immunoprecipitation and GST pulldown assays demonstrated association of LMBD1 with tubulin. Immunofluorescence staining also showed the colocalization of LMBD1 with microtubule in both interphase and mitotic cells. LMBD1 specifically accelerates microtubule assembly dynamics in vitro and antagonizes the microtubule-disruptive effect of vinblastine. In addition, LMBRD1-knockdown impairs mitotic spindle formation, inhibits tubulin polymerization, and diminishes the mitosis-associated tubulin acetylation. The reduced acetylation can be reversed by ectopic expression of LMBD1 protein. These results suggest that LMBD1 protein stabilizes microtubule intermediates. Furthermore, embryonic fibroblasts derived from Lmbrd1 heterozygous knockout mice showed abnormality in microtubule formation, mitosis, and cell growth. Taken together, LMBD1 plays a pivotal role in regulating microtubule assembly that is essential for the process of cell mitosis.

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