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Source: Biochemical Journal
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Total 25 results found since Jan 2013.
A novel small molecule A2A adenosine receptor agonist, indirubin-3'-monoxime, alleviates lipid-induced inflammation and insulin resistance in 3T3-L1 adipocytes
Saturated free fatty acid-induced adipocyte inflammation plays a pivotal role in implementing insulin resistance and type 2 diabetes. Recent reports suggest A2A adenosine receptor (A2AAR) could be an attractive choice to counteract adipocyte inflammation and insulin resistance. Thus, an effective A2AAR agonist devoid of any toxicity is highly appealing. Here, we report that indirubin-3'-monoxime (I3M), a derivative of the bisindole alkaloid indirubin, efficiently binds and activates A2AAR which leads to the attenuation of lipid-induced adipocyte inflammation and insulin resistance. Using a combination of in silico virtual ...
Source: Biochemical Journal - August 29, 2019 Category: Biochemistry Authors: Choudhary, S. A., Bora, N., Banerjee, D., Arora, L., Das, A. S., Yadav, R., Klotz, K.-N., Pal, D., Jha, A. N., Dasgupta, S. Tags: Research Articles Source Type: research
AMP-activated protein kinase complexes containing the {beta}2 regulatory subunit are up-regulated during and contribute to adipogenesis
This study therefore sought to determine the contribution of AMPKβ subunit isoforms to adipocyte biology, focussing on adipogenesis. AMPKβ2 was the principal AMPKβ isoform in 3T3-L1 adipocytes, isolated rodent adipocytes and human subcutaneous adipose tissue, as assessed by the contribution to total cellular AMPK activity. Down-regulation of AMPKβ2 with siRNA inhibited lipid accumulation, cellular adiponectin levels and adiponectin secretion during 3T3-L1 adipogenesis, whereas down-regulation of AMPKβ1 had no effect. Incubation of 3T3-L1 cells with MT47-100 selectively inhibited AMPK complexes cont...
Source: Biochemical Journal - June 25, 2019 Category: Biochemistry Authors: Katwan, O. J., Alghamdi, F., Almabrouk, T. A., Mancini, S. J., Kennedy, S., Oakhill, J. S., Scott, J. W., Salt, I. P. Tags: Research Articles Source Type: research
Histone demethylase KDM6B regulates human podocyte differentiation in vitro
In this study, we first examined the expression pattern of histone demethylase KDM6B at different times of cultured human podocytes in vitro. We found that the expression of KDM6B and podocyte differentiation markers WT1 and Nephrin are increased in the podocyte differentiation process. In cultured podocytes, KDM6B knockdown with siRNA impaired podocyte differentiation and led to expression down-regulation of WT1 and Nephrin. The treatment of podocytes with GSK-J4, a specific KDM6B inhibitor, can also obtain similar results. Overexpression of WT1 can rescue differentiated phenotype impaired by disruption of KDM6B. ChIP (ch...
Source: Biochemical Journal - June 25, 2019 Category: Biochemistry Authors: Guo, Y., Xiong, Z., Guo, X. Tags: Research Articles Source Type: research
Zinc induces iron uptake and DMT1 expression in Caco-2 cells via a PI3K/IRP2 dependent mechanism
The absorption of iron is influenced by numerous dietary and physiological factors. We have previously demonstrated that zinc treatment of intestinal cells increases iron absorption via induction of the apical membrane iron transporter divalent metal ion transporter-1 (DMT1). To better understand the mechanisms of zinc-induced iron absorption, we have studied the effect of zinc on iron uptake, iron transporter and iron regulatory protein (IRP 1 and 2) expression and the impact of the PI3K pathway in differentiated Caco-2 cells, an intestinal cell culture model. We found that zinc induces DMT1 protein and mRNA expression. Z...
Source: Biochemical Journal - June 10, 2019 Category: Biochemistry Authors: Kondaiah, P., Aslam, M. F., Mashurabad, P. C., Sharp, P. A., Pullakhandam, R. Tags: Research Articles Source Type: research
ZNF300 stimulates fatty acid oxidation and alleviates hepatosteatosis through regulating PPAR{alpha}
ZNF300 plays an important role in the regulation of HBV-related hepatocellular carcinoma. However, little is known about the role of ZNF300 in lipid metabolism and NAFLD. In the present study, we observed that ZNF300 expression was markedly decreased in free fatty acid (FFA)-induced fatty liver. Overexpressed ZNF300 alleviated hepatic lipid accumulation, whereas knockdown of ZNF300 enhanced the FFA-induced lipid accumulation. Investigations of the underlying mechanisms revealed that ZNF300 directly binds to and regulates the PPARα expression, thus promoting fatty acid oxidation. Furthermore, bisulfite pyrosequencing ...
Source: Biochemical Journal - January 31, 2019 Category: Biochemistry Authors: Yan, F.-J., Wang, Y.-J., Yan, S.-R., Lu, J., Zheng, Y.-L. Tags: Research Articles Source Type: research
Silencing of type II phosphatidylinositol 4-kinase {beta} stabilizes prostate apoptosis response-4 and induces apoptosis in cancer cells
Type II phosphatidylinositol 4-kinase β (PtdIns 4-kinase II β) is an enigma among the phosphatidylinositol 4-kinase family. The role of PtdIns 4-kinase II β in MCF-7 cells was addressed with the help of short hairpin RNA (shRNA). PtdIns 4-kinase II β shRNA transfection increased pan-caspase activity and induced apoptosis in cancerous MCF-7 cells. Non-cancerous MCF-10A cells were resistant to PtdIns 4-kinase II β shRNA-induced apoptosis. Caspase 8 and 9 inhibitors rescued MCF-7 cells from apoptosis. Shotgun proteomic studies with Flag-tagged PtdIns 4-kinase II β immunoprecipitates showed tumor ...
Source: Biochemical Journal - January 31, 2019 Category: Biochemistry Authors: Chaudhry, S., Joshi, V., Bojjireddy, N., Thoh, M., Sandur, S. K., Subrahmanyam, G. Tags: Research Articles Source Type: research
Exosomal KLF3-AS1 from hMSCs promoted cartilage repair and chondrocyte proliferation in osteoarthritis
The present study was designed to explore whether exosomal lncRNA-KLF3-AS1 derived from human mesenchymal stem cells (hMSCs) can serve as a positive treatment for osteoarthritis (OA). hMSCs and MSC-derived exosomes (MSC-exo) were prepared for morphological observation and identification by transmission electron microscopy and flow cytometry. IL-1β-induced OA chondrocytes and collagenase-induced rat model of OA were established for the further experiments. Lentivirus-mediated siRNA targeting KLF3-AS1 was transfected into MSCs for silencing KLF3-AS1. The real-time quantitative PCR and western blotting analysis were perf...
Source: Biochemical Journal - November 28, 2018 Category: Biochemistry Authors: Liu, Y., Zou, R., Wang, Z., Wen, C., Zhang, F., Lin, F. Tags: Research Articles Source Type: research
IFN-{gamma}-response mediator GBP-1 represses human cell proliferation by inhibiting the Hippo signaling transcription factor TEAD
Interferon-gamma (IFN-) is a pleiotropic cytokine that exerts important functions in inflammation, infectious diseases, and cancer. The large GTPase human guanylate-binding protein 1 (GBP-1) is among the most strongly IFN--induced cellular proteins. Previously, it has been shown that GBP-1 mediates manifold cellular responses to IFN- including the inhibition of proliferation, spreading, migration, and invasion and through this exerts anti-tumorigenic activity. However, the mechanisms of GBP-1 anti-tumorigenic activities remain poorly understood. Here, we elucidated the molecular mechanism of the human GBP-1-mediated suppre...
Source: Biochemical Journal - September 25, 2018 Category: Biochemistry Authors: Unterer, B., Wiesmann, V., Gunasekaran, M., Sticht, H., Tenkerian, C., Behrens, J., Leone, M., Engel, F. B., Britzen-Laurent, N., Naschberger, E., Wittenberg, T., Stürzl, M. Tags: Research Articles Source Type: research
Characterizing the interaction between insulin-like growth factor 2 mRNA-binding protein 1 (IMP1) and KRAS expression
Insulin-like growth factor 2 mRNA-binding protein-1 (IMP1) has high affinity for KRAS mRNA, and it can regulate KRAS expression in cells. We first characterized the molecular interaction between IMP1 and KRAS mRNA. Using IMP1 variants with a point mutation in the GXXG motif at each KH domain, we showed that all KH domains play a critical role in the binding of KRAS RNA. We mapped the IMP1-binding sites on KRAS mRNA and show that IMP1 has the highest affinity for nts 1–185. Although it has lower affinity, IMP1 does bind to other coding regions and the 3'-UTR of KRAS mRNA. Eight antisense oligonucleotides (AONs) were d...
Source: Biochemical Journal - September 5, 2018 Category: Biochemistry Authors: Mackedenski, S., Wang, C., Li, W.-M., Lee, C. H. Tags: Research Articles Source Type: research
MPC1 is essential for PGC-1{alpha}-induced mitochondrial respiration and biogenesis
In this study, we showed that MPC1 is down-regulated in human renal cell carcinoma (RCC) due to strong suppression of peroxisome proliferator-activated receptor-gamma co-activator (PGC)-1 alpha (PGC-1α). We also demonstrated that overexpression of PGC-1α stimulates MPC1 transcription, while depletion of PGC-1α by siRNA suppresses MPC expression. We found that PGC-1α interacts with estrogen-related receptor-alpha (ERR-α) and recruits it to the ERR-α response element motif located in the proximal MPC1 promoter, resulting in efficient activation of MPC1 expression. Furthermore, the MPC inhi...
Source: Biochemical Journal - May 18, 2018 Category: Biochemistry Authors: Koh, E., Kim, Y. K., Shin, D., Kim, K.-S. Tags: Research Articles Source Type: research
A transcription factor network represses CFTR gene expression in airway epithelial cells
Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause the inherited disorder cystic fibrosis (CF). Lung disease is the major cause of CF morbidity, though CFTR expression levels are substantially lower in the airway epithelium than in pancreatic duct and intestinal epithelia, which also show compromised function in CF. Recently developed small molecule therapeutics for CF are highly successful for one specific CFTR mutation and have a positive impact on others. However, the low abundance of CFTR transcripts in the airway limits the opportunity for drugs to correct the defective substrate. E...
Source: Biochemical Journal - April 16, 2018 Category: Biochemistry Authors: Mutolo, M. J., Leir, S.-H., Fossum, S. L., Browne, J. A., Harris, A. Tags: Research Articles Source Type: research
Phosphatase of regenerating liver maintains cellular magnesium homeostasis
Phosphatase of regenerating liver (PRL) is highly expressed in malignant cancers and promotes cancer progression. Recent studies have suggested its functional relationship with Mg2+, but the importance and molecular details of this relationship remain unknown. Here, we report that PRL expression is regulated by Mg2+ and PRL protects cells from apoptosis under Mg2+-depleted conditions. When cultured cells were subjected to Mg2+ depletion, endogenous PRL protein levels increased significantly. siRNA-mediated knockdown of endogenous PRL did not significantly affect cell proliferation under normal culture conditions, but it in...
Source: Biochemical Journal - March 26, 2018 Category: Biochemistry Authors: Yoshida, A., Funato, Y., Miki, H. Tags: Research Articles Source Type: research
Lipid-based DNA/siRNA transfection agents disrupt neuronal bioenergetics and mitophagy
A multitude of natural and artificial compounds have been recognized to modulate autophagy, providing direct or, through associated pathways, indirect entry points to activation and inhibition. While these pharmacological tools are extremely useful in the study of autophagy, their abundance also suggests the potential presence of unidentified autophagic modulators that may interfere with experimental designs if applied unknowingly. Here, we report unanticipated effects on autophagy and bioenergetics in neuronal progenitor cells (NPCs) incubated with the widely used lipid-based transfection reagent lipofectamine (LF), which...
Source: Biochemical Journal - November 10, 2017 Category: Biochemistry Authors: Napoli, E., Liu, S., Marsilio, I., Zarbalis, K., Giulivi, C. Tags: Research Articles Source Type: research
Constitutive activation of p46JNK2 is indispensable for C/EBP{delta} induction in the initial stage of adipogenic differentiation
Adipogenic differentiation plays a vital role in energy homeostasis and endocrine system. Several transcription factors, including peroxisome proliferator-activated receptor gamma 2 and CCAAT–enhancer-binding protein (C/EBP) α, β, and , are important for the process, whereas the stage-specific intracellular signal transduction regulating the onset of adipogenesis remains enigmatic. Here, we explored the functional role of c-jun N-terminal kinases (JNKs) in adipogenic differentiation using in vitro differentiation models of 3T3-L1 cells and primary adipo-progenitor cells. JNK inactivation with either a phar...
Source: Biochemical Journal - October 5, 2017 Category: Biochemistry Authors: Kusuyama, J., Ohnishi, T., Bandow, K., Amir, M. S., Shima, K., Semba, I., Matsuguchi, T. Tags: Research Articles Source Type: research
{gamma}-COPI mediates the retention of kAE1 G701D protein in Golgi apparatus - a mechanistic explanation of distal renal tubular acidosis associated with the G701D mutation
Mutations of the solute carrier family 4 member 1 (SLC4A1) gene encoding kidney anion (chloride/bicarbonate ion) exchanger 1 (kAE1) can cause genetic distal renal tubular acidosis (dRTA). Different SLC4A1 mutations give rise to mutant kAE1 proteins with distinct defects in protein trafficking. The mutant kAE1 protein may be retained in endoplasmic reticulum (ER) or Golgi apparatus, or mis-targeted to the apical membrane, failing to display its function at the baso-lateral membrane. The ER-retained mutant kAE1 interacts with calnexin chaperone protein; disruption of this interaction permits the mutant kAE1 to reach the cell...
Source: Biochemical Journal - July 17, 2017 Category: Biochemistry Authors: Duangtum, N., Junking, M., Phadngam, S., Sawasdee, N., Castiglioni, A., Charngkaew, K., Limjindaporn, T., Isidoro, C., Yenchitsomanus, P.-t. Tags: Research Articles Source Type: research
