• Title/Summary/Keyword: KDM6B

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AURKA Suppresses Leukemic THP-1 Cell Differentiation through Inhibition of the KDM6B Pathway

  • Park, Jin Woo;Cho, Hana;Oh, Hyein;Kim, Ji-Young;Seo, Sang-Beom
    • Molecules and Cells
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    • v.41 no.5
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    • pp.444-453
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    • 2018
  • Aberrations in histone modifications are being studied in mixed-lineage leukemia (MLL)-AF9-driven acute myeloid leukemia (AML). In this study, we focused on the regulation of the differentiation of the MLL-AF9 type AML cell line THP-1. We observed that, upon phorbol 12-myristate 13-acetate (PMA) treatment, THP-1 cells differentiated into monocytes by down-regulating Aurora kinase A (AURKA), resulting in a reduction in H3S10 phosphorylation. We revealed that the AURKA inhibitor alisertib accelerates the expression of the H3K27 demethylase KDM6B, thereby dissociating AURKA and YY1 from the KDM6B promoter region. Using Flow cytometry, we found that alisertib induces THP-1 differentiation into monocytes. Furthermore, we found that treatment with the KDM6B inhibitor GSK-J4 perturbed the PMA-mediated differentiation of THP-1 cells. Thus, we discovered the mechanism of AURKA-KDM6B signaling that controls the differentiation of THP-1 cells, which has implications for biotherapy for leukemia.

Effect of black chokeberry on skeletal muscle damage and neuronal cell death

  • Kim, Jisu;Lee, Kang Pa;Beak, Suji;Kang, Hye Ra;Kim, Yong Kyun;Lim, Kiwon
    • Korean Journal of Exercise Nutrition
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    • v.23 no.4
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    • pp.26-31
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    • 2019
  • [Purpose] Numerous epidemiological studies have shown that it is possible to prescribe exercise for neurodegenerative disease, such as Alzheimer's disease and Parkinson's disease. However, despite the availability of diverse scientific knowledge, the effects of exercise in this regard are still unclear. Therefore, this study attempted to investigate a substance, such as black chokeberry (Aronia melanocapa L.) that could improve the ability of the treatment and enhance the benefits of exercising in neurodegenerative diseases. [Methods] The cell viability was tested with 2,3-bis[2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolim-5-carboxanilide and the cells were stained with ethidium homodimer-1 solution. The mRNA expression levels were evaluated by microarray. The active compounds of black chokeberry ethanolic extract (BCE) were analyzed by gas chromatography. The chemical shift analysis in the brain was performed using magnetic resonance spectroscopy. [Results] BCE treatment decreased hydrogen peroxide-induced L6 cell death and beta amyloid induced primary neuronal cell death. Furthermore, BCE treatment significantly reduced the mRNA levels of the inflammatory factors, such as IL-1α, Cxcl13, IL36rn, Itgb2, Epha2, Slamf8, Itgb6, Kdm6b, Acvr1, Cd6, Adora3, Cd27, Gata3, Tnfrsf25, Cd40lg, Clec10a, and Slc11a1, in the primary neuronal cells. Next, we identified 16 active compounds from BCE, including D-mannitol. In vivo, BCE (administered orally at a dosage of 50 mg/kg) significantly regulated chemical shift in the brain. [Conclusion] Our findings suggest that BCE can serve as a candidate for neurodegenerative disease therapy owing to its cyto-protective and anti-inflammatory effects. Therefore, BCE treatment is expected to prevent damage to the muscles and neurons of the athletes who continue high intensity exercise. In future studies, it would be necessary to elucidate the effects of combined BCE intake and exercise.

Identification of loci affecting teat number by genome-wide association studies on three pig populations

  • Tang, Jianhong;Zhang, Zhiyan;Yang, Bin;Guo, Yuanmei;Ai, Huashui;Long, Yi;Su, Ying;Cui, Leilei;Zhou, Liyu;Wang, Xiaopeng;Zhang, Hui;Wang, Chengbin;Ren, Jun;Huang, Lusheng;Ding, Nengshui
    • Asian-Australasian Journal of Animal Sciences
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    • v.30 no.1
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    • pp.1-7
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    • 2017
  • Objective: Three genome-wide association studies (GWAS) and a meta-analysis of GWAS were conducted to explore the genetic mechanisms underlying variation in pig teat number. Methods: We performed three GWAS and a meta-analysis for teat number on three pig populations, including a White Duroc${\times}$Erhualian $F_2$ resource population (n = 1,743), a Chinese Erhualian pig population (n = 320) and a Chinese Sutai pig population (n = 383). Results: We detected 24 single nucleotide polymorphisms (SNPs) that surpassed the genome-wide significant level on Sus Scrofa chromosomes (SSC) 1, 7, and 12 in the $F_2$ resource population, corresponding to four loci for pig teat number. We highlighted vertnin (VRTN) and lysine demethylase 6B (KDM6B) as two interesting candidate genes at the loci on SSC7 and SSC12. No significant associated SNPs were identified in the meta-analysis of GWAS. Conclusion: The results verified the complex genetic architecture of pig teat number. The causative variants for teat number may be different in the three populations