Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Global transcriptional profile at a higher fermentation temperature in S.avermitilis NRRL8165

ABSTRACT: To explore the molecular mechanism of the positive thermoregulation on Jinggangmycin A biosynthesis, the transcriptomes of S. hygroscopicus 5008 cultivated at 30℃ or 37℃ in liquid medium were compared by microarray analysis. Additionally, the transcriptomes of S. avermitilis NRRL8165 cultivated at the same conditions were analyzed in parallel to filter transcriptional changes common to Streptomyces genus. Global gene expression in NRRL8165 was measured at 30℃ or 37℃, respectively. Three independent experiments were performed at each condition.

ORGANISM(S): Streptomyces avermitilis

SUBMITTER: hang wu

PROVIDER: E-GEOD-35611 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Purpose: We aimed to investigate the effect of several anti-leukemia drugs in combination with decitabine (DAC) on the proliferation of myeloid leukemia cells in vitro and in vivo, to select the most efficient combination group and explore associated mechanisms of these combination therapies. Experimental Design: After comparing with five anti-leukemia drugs in several different kinds of cell lines, the combination effect of idarubicin (IDA) with DAC was best. In vivo, by using microPET, TUNEL, and transmission electron microscopy, the inhibitory effects obtained by sequentially combining DAC with IDA, evidenced by evaluating tumor cell proliferation and cell apoptosis. Molecular studies were conducted using gene chip, which was used to explore associated pathways, and real-time quantitative reverse transcription-PCR, western blot and immunohistochemistry (IHC), used to assess regulation of Wnt/β-catenin pathway. Results: The sequential combination of DAC and IDA showed synergistic induction of cell death in U937, HEL, SKM-1 and cells isolated from AML patients. Importantly, the inhibition of tumor growth in the sequential combination group was found to be significantly higher than that of single drug group or control group in vivo. Moreover, sequential treatment with DAC and IDA induced apoptosis and depression of the Wnt/β-catenin pathway in both culture and animal studies. Conclusions: Our findings showed that sequentially combining decitabine with idarubicin had a synergistic anti-leukemia effect. These findings were attributed to demethylation of Wnt pathway inhibitors and downregulation of Wnt pathway nuclear targets observed in vitro and in vivo. After comparing with five anti-leukemia drugs in several different kinds of cell lines, the combination effect of idarubicin (IDA) with DAC was best. In vivo, by using microPET, TUNEL, and transmission electron microscopy, the inhibitory effects obtained by sequentially combining DAC with IDA, evidenced by evaluating tumor cell proliferation and cell apoptosis. Molecular studies were conducted using gene chip, which was used to explore associated pathways, and real-time quantitative reverse transcription-PCR, western blot and immunohistochemistry (IHC), used to assess regulation of Wnt/β-catenin pathway.

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Global transcriptional profile at a higher fermentation temperature in S.avermitilis NRRL8165

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