Project description:To investigate the antitumor mechanism of LSD1 inhibitor B35 on NSCLC, we collected A549 cells treated with B35(2μM) for 72 hours, then we performed gene expression profiling analysis using data obtained from RNA-seq of control cells or B35 treatment group
Project description:The presence of the HLA-B35 allele has emerged as an important risk factor for the development of isolated pulmonary hypertension (iPHT) in patients with Scleroderma (SSc), however the mechanisms underlying this association have not been fully elucidated. The goal of our study was to determine the molecular mechanisms that mediate the biological effects of HLA-B35 in endothelial cells (ECs). Our data demonstrate that HLA-B35 expression at the physiological levels using via adenoviral vector resulted in a significantly increased endothelin-1 (ET-1) and a significantly decreased endothelial nitric oxide synthase (eNOS) mRNA and protein levels. Furthermore, HLA-B35 greatly upregulated expression of cytoplasmic chaperones, including heat shock proteins (HSPs) HSP70 (HSPA1A and HSPA1B) and HSP40 (DNAJB1 and DNAJB9), suggesting that HLA-B35 induced the ER stress and unfolded protein response (UPR) in ECs. Examination of selected mediators of the UPR response, including BiP (GRP78), CHOP (GADD153), ERO1 (endoplasmic reticulum oxidase) and PDI (protein disulfide isomerase) has revealed a consistent increase of BiP expression levels. Accordingly, Thapsigargin (TG), a known ER stress inducer, stimulated ET-1 mRNA and protein levels in ECs. This study suggests that HLA-B35 could contribute to endothelial cell dysfunction via ER stress mediated induction of ET-1 in patients with PHT.
Project description:To assess the role of LSD1 in mice small intestinal epithelium, small intestinal organoids were treated with an inhibitor for LSD1 (GSK-LSD1) and compared to untreated organoids. Similar to intestinal epithelium from mice with an intestinal epithelium specific LSD1-KO, paneth cells dissappear upon GSK-LSD1 treatment. We used these sequencing data to show that these small intestinal organoids have a similar phenotype as mice epithelium without LSD1.
Project description:We screened for the changes in gene expression induced by an LSD1 inhibitor to elucidate the mechanism of its cytotoxic effect on T-cell acute lymphoblastic leukemia (T-ALL).
Project description:Lysine-specific demethylase 1 (LSD1) is an epigenetic enzyme that oxidatively cleaves methyl groups from monomethyl and dimethyl Lys4 of histone H3 (H3K4Me1, H3K4Me2) and can contribute to gene silencing. This study describes the design and synthesis of analogs of a monoamine oxidase antidepressant, phenelzine, and their LSD1 inhibitory properties. A novel phenelzine analog (bizine) containing a phenyl-butyrylamide appendage was shown to be a potent LSD1 inhibitor in vitro and was selective versus monoamine oxidases A/B and the LSD1 homolog, LSD2. LSD1 inhibitor bizine was found to be effective at modulating bulk histone methylation in cancer cells, and ChIP-seq experiments revealed a statistically significant overlap in the H3K4 methylation pattern of genes affected by bizine and those altered in LSD1-/- cells. Treatment of two cancer cell lines, LNCaP and H460 with bizine conferred a reduction in proliferation rate, and bizine showed additive to synergistic effects on cell growth when used in combination with two out of five HDAC inhibitors tested. Moreover, neurons exposed to oxidative stress were protected by the presence of bizine, suggesting potential applications in neurodegenerative disease.
Project description:Proteomic expression analysis of Ca. Lokiarchaeum ossiferum, strain B35, grown using casein hydrolysate as the main carbon source under anaerobic conditions
Project description:These proteomic data were produced in order to assess the effect of drug 3324, a pan-lysine demethylase inhibitor, on the estrogen receptor (ER) and Lysine Demethylase1 (LSD1)protein interaction networks.
Project description:The Nitroreductase NfsB (NTR) prodrug of an LSD1 inhibitor is inactive in wild-type THP1 cells, but the prodrug gets activated in the LSD1 inhibitor by the NTR in NTR-expressing THP1 cells (THP1-NTR+). Cell-type specific inhibition of LSD1 in THP1-NTR+ cells with a NTR prodrug is shown with the expression data of the two cell lines, THP1-wt and THP1-NTR+. Data for the LSD1 inhibitor and a negative control with both cell lines are included.