• Title/Summary/Keyword: LSD1

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LSD1-S112A exacerbates the pathogenesis of CSE/LPS-induced chronic obstructive pulmonary disease in mice

  • Jeong, Jiyeong;Oh, Chaeyoon;Kim, Jiwon;Yoo, Chul-Gyu;Kim, Keun Il
    • BMB Reports
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    • v.54 no.10
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    • pp.522-527
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    • 2021
  • Lysine-specific demethylase 1 (LSD1) is an epigenetic regulator that modulates the chromatin status, contributing to gene activation or repression. The post-translational modification of LSD1 is critical for the regulation of many of its biological processes. Phosphorylation of serine 112 of LSD1 by protein kinase C alpha (PKCα) is crucial for regulating inflammation, but its physiological significance is not fully understood. This study aimed to investigate the role of Lsd1-S112A, a phosphorylation defective mutant, in the cigarette smoke extract/LPS-induced chronic obstructive pulmonary disease (COPD) model using Lsd1SA/SA mice and to explore the potential mechanism underpinning the development of COPD. We found that Lsd1SA/SA mice exhibited increased susceptibility to CSE/LPS-induced COPD, including high inflammatory cell influx into the bronchoalveolar lavage fluid and airspace enlargement. Additionally, the high gene expression associated with the inflammatory response and oxidative stress was observed in cells and mice containing Lsd1-S112A. Similar results were obtained from the mouse embryonic fibroblasts exposed to a PKCα inhibitor, Go6976. Thus, the lack of LSD1 phosphorylation exacerbates CSE/LPS-induced COPD by elevating inflammation and oxidative stress.

Inhibition of LSD1 phosphorylation alleviates colitis symptoms induced by dextran sulfate sodium

  • Oh, Chaeyoon;Jeong, Jiyeong;Oh, Se Kyu;Baek, Sung Hee;Kim, Keun Il
    • BMB Reports
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    • v.53 no.7
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    • pp.385-390
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    • 2020
  • Inflammatory Bowel Disease is caused by an acute or chronic dysfunction of the mucosal inflammatory system in the intestinal tract. In line with the results of our previous study, wherein we found that the PKCα-LSD1-NF-κB signaling plays a critical role in the prolonged activation of the inflammatory response, we aimed to investigate the effect of signaling on colitis in the present study. Lsd1 S112A knock-in (Lsd1SA/SA) mice, harboring a deficiency in phosphorylation by PKCα, exhibited less severe colitis symptoms and a relatively intact colonic epithelial lining in dextran sulfate sodium (DSS)-induced colitis models. Additionally, a reduction in pro-inflammatory gene expression and immune cell recruitment into damaged colon tissues in Lsd1SA/SA mice was observed upon DSS administration. Furthermore, LSD1 inhibition alleviated colitis symptoms and reduced colonic inflammatory responses. Both LSD1 phosphorylation and its activity jointly play a role in the progression of DSS-induced colitis. Therefore, the inhibition of LSD1 activity could potentially protect against the colonic inflammatory response.

Kinetic Characterization of an Iron-sulfur Containing Enzyme, L-serine Dehydratase from Mycobacterium tuberculosis H37Rv (Mycobacterium tuberculosis H37Rv로부터 유래된 철-황 함유 효소인 L-세린 탈수화효소의 동력학적 특성)

  • Han, Yu Jeong;Lee, Ki Seog
    • Journal of Life Science
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    • v.28 no.3
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    • pp.351-356
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    • 2018
  • L-Serine dehydratase (LSD) is an iron-sulfur containing enzyme that catalyzes the conversion of L-serine to pyruvate and ammonia. Among the bacterial amino acid dehydratases, it appears that only the L-serine specific enzymes utilize an iron-sulfur cluster at their catalytic site. Moreover, bacterial LSDs are classified into four types based on structural characteristics and domain arrangement. To date, only the LSD enzymes from a few bacterial strains have been studied, but more detailed investigations are required to understand the catalytic mechanism of various bacterial LSDs. In this study, LSD type II from Mycobacterium tuberculosis (MtLSD) H37Rv was expressed and purified to elucidate the biochemical and catalytic properties using the enzyme kinetic method. The L-serine saturation curve of MtLSD exhibited a typically sigmoid character, indicating an allosteric cooperativity. The values of $K_m$ and $k_{cat}$ were estimated to be $59.35{\pm}1.23mM$ and $18.12{\pm}0.20s^{-1}$, respectively. Moreover, the plot of initial velocity versus D-serine concentration at fixed L-serine concentrations showed a non-linear hyperbola decay shape and exhibited a competitive inhibition for D-serine with an apparent $K_i$ value of $30.46{\pm}5.93mM$ and with no change in the $k_{cat}$ value. These results provide insightful biochemical information regarding the catalytic properties and the substrate specificity of MtLSD.

Downregulation of JMJD2a and LSD1 is involved in CK2 inhibition-mediated cellular senescence through the p53-SUV39h1 pathway

  • Park, Jeong-Woo;Bae, Young-Seuk
    • BMB Reports
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    • v.55 no.2
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    • pp.92-97
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    • 2022
  • Lysine methylation is one of the most important histone modifications that modulate chromatin structure. In the present study, the roles of the histone lysine demethylases JMJD2a and LSD1 in CK2 downregulation-mediated senescence were investigated. The ectopic expression of JMJD2a and LSD1 suppressed the induction of senescence-associated β-galactosidase activity and heterochromatin foci formation as well as the reduction of colony-forming and cell migration ability mediated by CK2 knockdown. CK2 downregulation inhibited JMJD2a and LSD1 expression by activating the mammalian target of rapamycin (mTOR)-ribosomal p70 S6 kinase (p70S6K) pathway. In addition, the down-regulation of JMJD2a and LSD1 was involved in activating the p53-p21Cip1/WAF1-SUV39h1-trimethylation of the histone H3 Lys9 (H3K9me3) pathway in CK2-downregulated cells. Further, CK2 downregulation-mediated JMJD2a and LSD1 reduction was found to stimulate the dimethylation of Lys370 on p53 (p53K370me2) and nuclear import of SUV39h1. Therefore, this study indicated that CK2 downregulation reduces JMJD2a and LSD1 expression by activating mTOR, resulting in H3K9me3 induction by increasing the p53K370me2-dependent nuclear import of SUV39h1. These results suggest that CK2 is a potential therapeutic target for age-related diseases.

Lumpy skin disease as an emerging infectious disease

  • Hye Jin Eom;Eun-Seo Lee;Han Sang Yoo
    • Journal of Veterinary Science
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    • v.24 no.3
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    • pp.42.1-42.6
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    • 2023
  • Lumpy skin disease (LSD) is one of the most important emerging transboundary diseases. Recently, LSD has emerged in many countries in the northern hemisphere. The LSD virus has a huge genome and is highly resistant to environmental conditions. The virus is also host-specific and large ruminants, such as cattle and domestic water buffalo, are particularly susceptible. In addition, wild ruminants can serve as potential reservoirs for spreading the LSD virus. The emergence might be related to climate change in various regions because LSD is an arthropod-borne infectious disease. This disease causes enormous economic losses, such as leather damage, decreased milk production, abortion, and death in infected ruminants. The economic importance of LSD in the bovine industry has forced countries to develop and implement control strategies against the disease. With the recent global spread and the economic impact, LSD will be discussed intensively. In addition, effective preventive measures are suggested based on the presence or absence of LSD outbreaks.

Cloning of the dextranase gene(lsd11) from Lipomyces starkeyi and its expression in Pichia pastoris.

  • Park, Ji-Young;Kang, Hee-Kyoung;Jin, Xing-Ji;Ahn, Joon-Seob;Kim, Seung-Heuk;Kim, Do-Won;Kim, Do-Man
    • 한국생물공학회:학술대회논문집
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    • 2005.10a
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    • pp.644-648
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    • 2005
  • Dextranase (${\alpha}$-1,6-D-glucan-6-glucanogydrolase:E.C. 3.2.1.11) catalyzes the hydrolysis of ${\alpha}$-(1.6) linkages of dextran. A lsd1 gene encoding an extracellular dextranase was isolated from the genomic DNA of L. starkeyi. The lsd11 gene is a synthetic dextranase (lsd1) after codon optimization for gene expression with Pichia pastoris system. A open reading frame of lsd11 gene was 1827 bp and it was inserted into the pPIC3.5K expression vector. The plasmid linearized by Sac I was integrated into the 5'AOX region of the chromosomal DNA of P. pastoris. The lsd11 gene fragment encoding a mature protein of 608 amino acids with a predicted molecular weight of 70 kDa, was expressed in the methylotrophic yeast P. pastoris by controling the alcohol oxidase-1 (AOX1) promoter. The recombinant lds11 was optimized by using the shake-flask expression and upscaled using fermentation technology. More than 9.8 mg/L of active dextranase was obtained after induction by methanol. The optimum pH of LSD11 was found to be 5.5 and the optimum temperature $28^{\circ}C$.

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A Study on the Development of Limited Slip Differential on All Terrain Vehicle (사륜구동 오토바이(ATV)용 차동제한장치(LSD) 개발에 관한 연구)

  • Kim, Jun-An;Jun, Jae-Uhk
    • Journal of the Korean Society of Manufacturing Process Engineers
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    • v.10 no.1
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    • pp.8-15
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    • 2011
  • ATV(All Terrain Vehicle) has been developed to be used for agricultural fields on unpaved roads but now it is mostly used to transport a short distance and play leisure sports at mountains. Recently, main concerns on the automobile industry is developing not only a car safe, high fuel efficient and friendly related with environment but also two-wheeled vehicles. In order to maintain high fuel efficiency and safety of two-wheeled vehicle, it is essential that ATV should be set up differential gear. But we worried for ATV which had been set up differential gear not to run on unpaved roads. Therefore, it is necessary to develop LSD(Limited Slip Differential) that maintains existing advantages of ATV and ensures ATV to travel safely on roads. Now LSD equipped cars have a complicated structure, so setting up on ATV is unsuitable. Therefore, in this study, we have developed simple, small and well operating LSD.

The Relationship Between Hip Abductor and Pelvic Drop During Lateral Step Down in the Elderly

  • Lee, Young-kwon;Jung, Sung-hoon;Yoo, Hwa-ik;Kwon, Oh-yun
    • Physical Therapy Korea
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    • v.29 no.4
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    • pp.249-254
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    • 2022
  • Background: The lateral step down (LSD) is a form of stair negotiation used by the elderly because it requires less movement of the lower extremity. Although it is necessary to study the amount of pelvic drop and the strength of a hip abductor during LSD for intervention, limited studies have investigated the relationship between the amount of pelvic drop and strength of a hip abductor during LSD in elderly people. Objects: This study aimed to determine the relationship between the amount of pelvic drop on an unsupported leg and the strength of the hip abductor during LSD in the elderly. Methods: Thirty elderly people (male: 17, female: 13) were recruited. Subjects performed the LSD task, and the evaluator measured and the amount of pelvic drop on an unsupported side. Also, the isometric strength of the hip abductor was measured in a supine position. Results: We found significant relationships between the strength of the hip abductor and the amount of pelvic drop (r = -0.386). The average hip abductor strength normalized by body weight was 1.06 N/kg (max: 1.99, min: 0.52) and the average contralateral pelvic drop (CPD) angle was 4.16° (max: 15.3, min: 0). Conclusion: Our results indicated that the strength of the hip abductor had a moderate correlation with the CPD during a LSD in the elderly. Hip abductor weakness could translate into altered movement of the pelvis.

Identification of a host range determinant from Ralstonia solancearum race 3

  • Yeonhwa Jeong;Lee, Seungdon;Ingyu Hwang
    • Proceedings of the Korean Society of Plant Pathology Conference
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    • 2003.10a
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    • pp.71.2-71
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    • 2003
  • Ralstonia solancearum infects many solanaceous plants, however race 3 infects only potato and tomato weakly. To identify genes responsible for race specificity of R. solanacearum, we mobilized genomic library of LSD2029 (race 3) into LSD341 (race 1) and inoculated 1,000 transconjugants into hot pepper. One transconjugant that did not induce wilt symptom in hot pepper was isolated. We found that a cosmid clone, pRSl, conferred avirulence to LSD341. By deletion and mutational analyses of pRSl, we found the 0.9-kb PstI/Hindlll fragment carries avirulence functions. We sequenced the fragment and identified one possible open reading frame, a rsal gene, possibly encoding 110 amino acids. The rsal was preceded with a plant-inducible promoter (PIP) box, indicating that the gene might be regulated by HrpB. Interestingly, the promoter region of the rsal homolog in the strain GM11000 (race 1) did not have the PIP box. Rsal did not show any significant homologies with proteins in the database, indicating th e protein is different from the previously reported avirulence proteins. When we mutated the rsal gene by marker-exchange in LSD2029, the mutant was less virulent in potato.

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