Biochemical and biophysical research communications
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Biochem. Biophys. Res. Commun. · Aug 2013
High glucose induces activation of NF-κB inflammatory signaling through IκBα sumoylation in rat mesangial cells.
The posttranslational modification of proteins by small ubiquitin-like modifiers (SUMOs) has emerged as an important regulatory mechanism for the alteration of protein activity, stability, and cellular localization. The latest research demonstrates that sumoylation is extensively involved in the regulation of the nuclear factor κB (NF-κB) pathway, which plays a critical role in the regulation of inflammation and contributes to fibrosis in diabetic nephropathy (DN). However, the role of sumoylation in the regulation of NF-κB signaling in DN is still unclear. ⋯ However, the expression of IκBα sumoylation in high glucose was significantly decreased compared with the normal glucose group (p<0.05). The expression of IκBα was dose- and time-dependently decreased, and NF-κBp65 and MCP-1 were increased under high glucose conditions, which could be mostly reversed by adding MG132 (p<0.05). The present results support the hypothesis that high glucose may activate NF-κB inflammatory signaling through IκBα sumoylation and ubiquitination.
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Biochem. Biophys. Res. Commun. · Aug 2013
miR-18b inhibits TGF-β1-induced differentiation of hair follicle stem cells into smooth muscle cells by targeting SMAD2.
Human hair follicle mesenchymal stem cells (hHF-MSCs) are capable of differentiating into smooth muscle cells (SMCs) in response to transforming growth factor-β (TGF-β), and thus can be used for cardiovascular tissue engineering and regenerative medicine. However, the precise molecular mechanisms underlying SMC conversion of hHF-MSCs are still undefined. MicroRNAs (miRNAs) are small noncoding RNAs that modulate gene expression post-transcriptionally by binding to the complementary sequences of targeted mRNAs. ⋯ We also showed that SMAD2, a key transcription regulator in TGF-β signaling which was involved in SMC differentiation, is regulated by miR-18b. miR-18b could suppress the expression of SMAD2 protein by targeting the 3'UTR of SMAD2 gene without affecting its mRNA level in hHF-MSCs. Moreover, knockdown of SMAD2 by RNA interference could block the effect of inhibition of miR-18b on SMC differentiation, indicating that SMAD2 contributed to miR-18b mediated regulation of TGF-β-induced SMC differentiation. In conclusion, this study demonstrated that miR-18b regulated the TGF-β1-induced differentiation of hHF-MSCs into SMCs by targeting SMAD2 gene, and provided novel insights into the regulatory mechanisms of TGF-β-induced SMC differentiation.
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Biochem. Biophys. Res. Commun. · Aug 2013
Deletion of the Basigin gene results in reduced mitochondria in the neural retina.
Basigin-null mice are characterized as blind from the time of eye opening, with degeneration of the retina beginning at 8weeks of age, and progressing until the entire photoreceptor cell layer is destroyed. It is likely that a metabolic deficiency underlies the blindness and degeneration phenotypes, as it has been determined that Basigin-null mice do not express the transporter protein monocarboxylate transporter one on the membrane of photoreceptor cells and inner segments, nor Müller cells of the neural retina, as is observed in normal mice. The purpose of the present study was to assess the health of mitochondria in normal and Basigin-null mice, specifically to determine if mitochondria within the Basigin-null mouse neural retina are metabolically active. ⋯ It was determined that cytochrome C concentrations and expression of autophagy-specific proteins were not increased in Basigin-null animals, as compared to control animals. Also, while Basigin-null mice do have metabolically active mitochondria, the amount of mitochondria was greatly reduced, when compared to control animals. The results suggest that a reduction in mitochondria is a result, rather than the cause, of the metabolic deficiency observed in Basigin-null mice, and likely occurs because of reduced metabolic activity in the absence of MCT1 expression.
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Biochem. Biophys. Res. Commun. · Aug 2013
CD19 target-engineered T-cells accumulate at tumor lesions in human B-cell lymphoma xenograft mouse models.
Adoptive T-cell therapy with CD19-specific chimeric antigen receptors (CARs) is promising for treatment of advanced B-cell malignancies. Tumor targeting of CAR-modified T-cells is likely to contribute therapeutic potency; therefore we examined the relationship between the ability of CD19-specific CAR (CD19-CAR)-transduced T-cells to accumulate at CD19(+) tumor lesions, and their ability to provide anti-tumor effects in xenograft mouse models. ⋯ Furthermore, these cells efficiently accumulated at Raji tumor lesions where they suppressed tumor progression and prolonged survival in tumor-bearing Rag2(-/-)γc(-/-) immunodeficient mice compared to control cohorts. These results show that the ability of CD19-CAR T-cells to home in on tumor lesions is pivotal for their anti-tumor effects in our xenograft models, and therefore may enhance the efficacy of adoptive T-cell therapy for refractory B-cell lymphoma.
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Biochem. Biophys. Res. Commun. · Aug 2013
Vesicular nucleotide transporter is involved in ATP storage of secretory lysosomes in astrocytes.
Recent studies have suggested that astrocytes release gliotransmitters (i.e., ATP, L-glutamate, D-serine, and peptide hormones) and participate actively in synaptic functioning. Although ATP release from astrocytes modulates the activity of neurons, the mechanisms regulating the ATP release from astrocytes and the source of ATP in astrocytes are not well understood. Recently a vesicular nucleotide transporter (VNUT)/solute carrier family 17, member 9 (SLC17A9) has been identified as a mediator of the active accumulation of ATP into vesicles. ⋯ We also found that inhibition of VNUT function by Evans Blue decreased ATP uptake into secretory lysosomes. Depletion and inhibition of endogenous VNUT by small interference RNA and Evans Blue, respectively decreased the amount of ATP release from the cells, whereas overexpression of VNUT increased it. Taken together, these findings indicate that the participation of VNUT in ATP storage in secretory lysosomes during lysosomal exocytosis of ATP from astrocytes.