No abstract

YH. Purple corn anthocyanins inhibit diabetes-associated glomerular monocyte activation and macrophage infiltration.

a b s t r a c tDifferentiation of preadipocytes into adipocytes is controlled by various transcription factors. Recently, the pro-adipogenic function of XBP1, a transcription factor upregulated by endoplasmic reticulum stress, has been reported. In this study, we demonstrated that XBP1 suppresses the expression of Wnt10b, an anti-adipogenic Wnt, during the differentiation of 3T3-L1 preadipocytes. The expression pattern of XBP1 was reciprocal to that of Wnt10b during the early stage of adipogenesis. The intracellular protein levels of b-catenin were negatively regulated by XBP1. Direct binding of XBP1 to the Wnt10b promoter and the subsequent decrease of the b-catenin signalling pathway represent a novel adipogenic differentiation mechanism.

X‐box binding protein 1 (XBP1), a transcription factor of the unfolded protein response, plays various roles in many biological processes. We examined its pro‐adipogenic activity and target genes during adipogenic differentiation in wild‐type and genetically modified 3T3‐L1 cells. Signalling pathways that contribute to Xbp1 mRNA splicing, and the correlation of the transcriptionally active XBP1 isoform (XBP1s) level with body mass index and the level of peroxisome proliferator‐activated receptor γ2 (PPARγ2) in human adipose tissues were also examined. The mRNA and nuclear protein expression levels of XBP1s increased immediately following hormonal induction of adipogenesis, reaching a peak at 6 h. Results from cDNA microarray and gene expression analyses using genetically modified cells indicated that PPARγ2 was a principal target of XBP1s. The XBP1s‐specific binding motif, which is distinct from the CCAAT/enhancer‐binding protein α binding site, was identified in the PPARγ2 promoter by site‐directed mutagenesis. Fetal bovine serum, insulin, 3‐isobutyl‐1‐methylxanthine and dexamethasone contributed independently to Xbp1 mRNA splicing. In human subcutaneous adipose tissues, the levels of both Xbp1s and Pparγ2 mRNA increased proportionally with body mass index, and there was a significant positive correlation between the two genes. These data suggest for the first time that positive regulation of PPARγ2 is a principal mechanism of XBP1s‐mediated adipogenesis in 3T3‐L1 cells.

Triphenylmethane dyes are aromatic xenobiotic compounds that are widely considered to be one of the main culprits of environmental pollution. Triphenylmethane reductase (TMR) from Citrobacter sp. strain KCTC 18061P was initially isolated and biochemically characterized as an enzyme that catalyzes the reduction of triphenylmethane dyes. Information from the primary amino acid sequence suggests that TMR is a dinucleotidebinding motif-containing enzyme; however, no other functional clues can be derived from sequence analysis. We present the crystal structure of TMR in complex with NADP ؉ at 2.0-Å resolution. Despite limited sequence similarity, the enzyme shows remarkable structural similarity to short-chain dehydrogenase/ reductase (SDR) family proteins. Functional assignments revealed that TMR has features of both classic and extended SDR family members and does not contain a conserved active site. Thus, it constitutes a novel class of SDR family proteins. On the basis of simulated molecular docking using the substrate malachite green and the TMR/NADP ؉ crystal structure, together with site-directed mutagenesis, we have elucidated a potential molecular mechanism for triphenylmethane dye reduction.