Mouse Knockout Models of Biliary Epithelial Cell Formation and Disease
Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso in The Pathophysiology of Biliary Epithelia, 2020
Hepatocytes undergo a transition from a hepatic endodermal epithelum to a nonpolarized cellidar phenotype (hepatoblasts) and then back to a fully differentiated epithelium. By E17, hepatocytes have developed their characteristic cuboidal cell morphology and, are ready to undergo the transition from a hemopoietic support role to primary cells controlling metabolite and serum protein levels. During this perinatal phase, the hepatocytes begin to express many new genes under the control of the transcription factor C/EBPbeta. (CCAAT/enhancer binding protein. They also form the cell junctions that are required to create a polarized epithelium, with the apical cell surface being the site of bile secretion and the basal cell surface opposed to the endothelial cells.
Familial Acute Myeloid Leukemia
Dongyou Liu in Handbook of Tumor Syndromes, 2020
The CCAAT/enhancer binding protein (C/EBP), alpha gene (CEBPA) is a single exon gene located on chromosome 19q13.1 band. The gene belongs to a family of basic leucine zipper proteins, and encodes for a transcription factor that is crucial for maturation of hematopoietic myeloid cells; no mature granulocytes are observed in CEBPA-mutant mice and the t(8;21) translocation downregulates CEBPA to lead to AML [35–37]. The CEBPA gene has 2 transactivation domains at the N-terminus, and a basic region and leucine zipper region at the C-terminus. Mutations in CEBPA may be present in sporadic AML in 5%–14% cases. Most commonly, mutations in the N-terminus cause a frameshift, leading to premature termination and absence of the normal, full-length 42 kDa protein, but still allowing downstream expression for formation of the smaller 30 kDa protein, a dominant-negative isoform. Mutations in the C-terminus disrupt the leucine zipper region, which prevents dimerization and loss of DNA activity [36].
Increasing the Sensitivity of Adipocytes and Skeletal Muscle Cells to Insulin
Christophe Wiart in Medicinal Plants in Asia for Metabolic Syndrome, 2017
Ethanol extract of Dioscorea opposita L. given orally to Sprague–Dawley rats at a dose of 300 mg/kg/day for 2 weeks prevented insulin resistance induced by subcutaneous injection of dexamethasone as evidenced by a decrease of plasma glucose from 9.5 to 2.8 mM (normal: 4.5 mM) and insulinemia from 0.7 to 0.2 nM (normal: 0.09 nM), respectivley.338 The extract lowered 30 minutes peak glycemia in oral glucose tolerance test.338 The extract at a concentration of 50 μg/mL increased insulin-mediated glucose uptake by 3T3-L1 adipocytes by 5 folds together with increased expression of glucose transporter-4.338 (4E,6E)-1,7-bis(4-hydroxyphenyl)-4, 6-heptadien-3-one, (3R,5R)-3,5-dihydroxy-1,7-bis(4-hydroxyphenyl)-3,5-heptanediol, batatasin I, (1E,4E,6E)-1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one isolated from the rhizomes of Dioscorea oppositifolia L. at a concentration of 20 μM inhibited the accumulation of triglycerides in dexamethasone-insulin-3-isobutyl-1-methylxanthine-induced differentiating 3T3-L1 preadipocytes concurrent decreased expression of peroxisome proliferator-activated receptor-γ.339 Batatasin I and (1E,4E,6E)-1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one down-regulated the expression of CCAAT/enhancer-binding protein-α.338 (4E,6E)-1,7-bis(4-hydroxyphenyl)-4,6-heptadien-3-one and batatasin I induced the phosphorylation of adenosine monophosphate-activated protein kinase.338 Batasin I boosted the expression of carnitine palmitoyltransferase-1.338
CEBPA mutants down-regulate AML cell susceptibility to NK-mediated lysis by disruption of the expression of NKG2D ligands, which can be restored by LSD1 inhibition
Published in OncoImmunology, 2022
Meng Liu, Mengbao Du, Jian Yu, Zijun Qian, Yang Gao, Wenjue Pan, Xiujie Zhao, Mowang Wang, Huimin Li, Jiaqi Zheng, Qianshuo Huang, Li-Mengmeng Wang, Haowen Xiao
CCAAT/enhancer-binding protein α (C/EBPα) is one of the most studied lineage-specific transcription factors (TFs) in hematopoiesis, which is mainly involved in cell fate decisions, including a key role in governing myeloid differentiation.1 In line with the critical role of C/EBPα in granulocytic differentiation, the CEBPA gene was found to be mutated in approximately 7% of all patients with acute myeloid leukemia (AML), and the incidence increased to 10–15% in AML patients with normal karyotype.2 Full-length C/EBPα is a 42-kDa protein (C/EBPα-p42) that contains two transactivation domains (TAD, TAD1 and TAD2) in the amino terminus and a basic leucine zipper domain (bZIP) at its carboxy terminus for DNA binding. Two major categories of collaborating CEBPA mutations have been described in human AML: (1) frameshift (FS) insertions or deletions affecting the N-terminal region resulting in a loss of the 42-kDa protein and overexpression of a shorter 30-kDa isoform (C/EBPα-p30), proposed to exhibit a dominant negative activity, and (2) in-frame mutations in the C-terminal region that alter the basic leucine zipper domain, leading to impaired DNA binding and disrupted protein–protein interactions.3 Furthermore, it has been shown that nearly 10% of AMLs with biallelic mutations in CEBPA also harbor a germline CEBPA mutation.4 These germline mutations are commonly additional C-terminal CEBPA mutations.5,6 So CEBPA mutations may be clustered to germline mutations, N-terminal frameshift mutations and C-terminal mutations.
Attenuation of obesity related inflammation in RAW 264.7 macrophages and 3T3-L1 adipocytes by varanadi kashayam and identification of potential bioactive molecules by UHPLC-Q-Orbitrap HRMS
Published in Archives of Physiology and Biochemistry, 2023
J. U. Chinchu, Mohind C. Mohan, B. Prakash Kumar
Obesity is a major health problem characterised by excessive body fat accumulation through an imbalance between energy intake and consumption and is responsible for developing type 2 diabetes, coronary heart disease and certain cancers (Guyenet and Schwartz 2012). Obesity is mainly associated with an increase in white adipose tissue mass through activation of adipogenesis and increased deposition of cytoplasmic triglycerides (Frigolet et al. 2008). Adipogenesis is a highly regulated process in which undifferentiated fibroblasts (preadipocytes) become mature adipocytes and is regulated by an elaborate network of transcription factors including CCAAT/enhancer-binding protein (C/EBP) and peroxisome proliferator-activated receptor-γ (PPAR-γ) (Yu et al. 2014). C/EBP-α and PPAR-γ work cooperatively in inducing the adipocyte differentiation process and promote the expression of fatty acid synthase (FAS) to trigger the synthesis and accumulation of triglyceride (TG) in mature adipocyte (Farmer 2006). Therefore, adipogenesis inhibition by downregulating adipogenic transcriptional factor expressions is critical for achieving an anti-obesity effect.
Combined effect of retinoic acid and calcium on the in vitro differentiation of human adipose-derived stem cells to adipocytes
Published in Archives of Physiology and Biochemistry, 2018
Farjam Goudarzi, Arash Sarveazad, Maryam Mahmoudi, Adel Mohammadalipour, Reza Chahardoli, Obeid M. Malekshah, Shiva Karimi Gorgani, Ali Akbar Saboor-Yaraghi
Among them, various transcriptional factors such as CCAAT-enhancer-binding protein alpha (C/EBPA) and CCAAT-enhancer-binding protein beta (C/EBPB) are important to regulate all pro-adipogenic cell signaling pathways and differentiation of the preadipocytes into the mature cells (Morrison and Farmer 2000, Guo et al. 2015). Their regulatory function is accomplished with the participation of genes such as peroxisome proliferator-activated receptor gamma (PPARG), a master regulator of adipogenesis (Tzameli et al. 2004).
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