• Title/Summary/Keyword: Research center

Search Result 59,792, Processing Time 0.07 seconds

Dysfunctional pancreatic cells differentiated from induced pluripotent stem cells with mitochondrial DNA mutations

  • So, Seongjun;Lee, Song;Lee, Yeonmi;Han, Jongsuk;Kang, Soonsuk;Choi, Jiwan;Kim, Bitnara;Kim, Deokhoon;Yoo, Hyun-Ju;Shim, In-Kyong;Oh, Ju-Yun;Lee, Yu-Na;Kim, Song-Cheol;Kang, Eunju
    • BMB Reports
    • /
    • v.55 no.9
    • /
    • pp.453-458
    • /
    • 2022
  • Diabetes mellitus (DM) is a serious disease in which blood sugar levels rise abnormally because of failed insulin production or decreased insulin sensitivity. Although many studies are being conducted for the treatment or early diagnosis of DM, it is not fully understood how mitochondrial genome (mtDNA) abnormalities appear in patients with DM. Here, we induced iPSCs from fibroblasts, PBMCs, or pancreatic cells of three patients with type 2 DM (T2D) and three patients with non-diabetes counterpart. The mtDNA mutations were detected randomly without any tendency among tissues or patients. In T2D patients, 62% (21/34) of iPSC clones harbored multiple mtDNA mutations, of which 37% were homoplasmy at the 100% mutation level compared to only 8% in non-diabetes. We next selected iPSC clones that were a wild type or carried mutations and differentiated into pancreatic cells. Oxygen consumption rates were significantly lower in cells carrying mutant mtDNA. Additionally, the mutant cells exhibited decreased production of insulin and reduced secretion of insulin in response to glucose. Overall, the results suggest that screening mtDNA mutations in iPSCs from patients with T2D is an essential step before pancreatic cell differentiation for disease modeling or autologous cell therapy.

Long-term depletion of cereblon induces mitochondrial dysfunction in cancer cells

  • Park, Seulki;Kim, Kidae;Haam, Keeok;Ban, Hyun Seung;Kim, Jung-Ae;Park, Byoung Chul;Park, Sung Goo;Kim, Sunhong;Kim, Jeong-Hoon
    • BMB Reports
    • /
    • v.54 no.6
    • /
    • pp.305-310
    • /
    • 2021
  • Cereblon (CRBN) is a multi-functional protein that acts as a substrate receptor of the E3 ligase complex and a molecular chaperone. While CRBN is proposed to function in mitochondria, its specific roles are yet to be established. Here, we showed that knockdown of CRBN triggers oxidative stress and calcium overload in mitochondria, leading to disruption of mitochondrial membrane potential. Notably, long-term CRBN depletion using PROteolysis TArgeting Chimera (PROTAC) induced irreversible mitochondrial dysfunction, resulting in cell death. Our collective findings indicate that CRBN is required for mitochondrial homeostasis in cells.

The role of autophagy in cell proliferation and differentiation during tooth development

  • Ji-Yeon Jung;Shintae Kim;Yeon-Woo Jeong;Won-Jae Kim
    • International Journal of Oral Biology
    • /
    • v.48 no.4
    • /
    • pp.33-44
    • /
    • 2023
  • In this review, the regulatory mechanisms of autophagy were described, and its interaction with apoptosis was identified. The role of autophagy in embryogenesis, tooth development, and cell differentiation were also investigated. Autophagy is regulated by various autophagy-related genes and those related to stress response. Highly active autophagy occurrences have been reported during cell differentiation before implantation after fertilization. Autophagy is involved in energy generation and supplies nutrients during early birth, essential to compensate for their deficient supply from the placenta. The contribution of autophagy during tooth development, such as the shape of the crown and root formation, ivory, and homeostasis in cells, was also observed. Genes control autophagy, and studying the role of autophagy in cell differentiation and development was useful for understanding human aging, illness, and health. In the future, the role of specific mechanisms in the development and differentiation of autophagy may increase the understanding of the pathological mechanisms of disease and development processes and is expected to reduce the treatment of various diseases by modulating the autophagic phenomenon.

Genome-wide Drug-induced Haploinsufficiency Screening of Fission Yeast for Identification of Hydrazinocurcumin Targets

  • Baek, Seung-Tae;Kim, Dong-Uk;Han, Sang-Jo;Woo, Im-Sun;Nam, Mi-Young;Kim, Li-La;Heo, Kyung-Sun;Lee, Hye-Mi;Hwang, Hye-Rim;Choi, Shin-Jung;Won, Mi-Sun;Lee, Min-Ho;Park, Song-Kyu;Lee, Sung-Hou;Kwon, Ho-Jeong;Maeng, Pil-Jae;Park, Hee-Moon;Park, Young-Woo;Kim, Dong-Sup;Hoe, Kwang-Lae
    • Journal of Microbiology and Biotechnology
    • /
    • v.18 no.2
    • /
    • pp.263-269
    • /
    • 2008
  • Hydrazinocurcumin (HC), a synthetic derivative of curcumin, has been reported to inhibit angiogenesis via unknown mechanisms. Understanding the molecular mechanisms of the drug's action is important for the development of improved compounds with better pharmacological properties. A genome-wide drug-induced haploinsufficiency screening of fission yeast gene deletion mutants has been applied to identify drug targets of HC. As a first step, the 50% inhibition concentration $(IC_{50})$ of HC was determined to be $2.2{\mu}M$. The initial screening of 4,158 mutants in 384-well plates using robotics was performed at concentrations of 2, 3, and $4{\mu}M$. A second screening was performed to detect sensitivity to HC on the plates. The first screening revealed 178 candidates, and the second screening resulted in 13 candidates, following the elimination of 165 false positives. Final filtering of the condition-dependent haploinsufficient genes gave eight target genes. Analysis of the specific targets of HC has shown that they are related to septum formation and the general transcription processes, which may be related to histone acetyltransferase. The target mutants showed 65% growth inhibition in response to HC compared with wild-type controls, as shown by liquid culture assay.

Isolation and Characterization of a Novel Calcium/Calmodulin-Dependent Protein Kinase, AtCK, from Arabidopsis

  • Jeong, Jae Cheol;Shin, Dongjin;Lee, Jiyoung;Kang, Chang Ho;Baek, Dongwon;Cho, Moo Je;Kim, Min Chul;Yun, Dae-Jin
    • Molecules and Cells
    • /
    • v.24 no.2
    • /
    • pp.276-282
    • /
    • 2007
  • Protein phosphorylation is one of the major mechanisms by which eukaryotic cells transduce extracellular signals into intracellular responses. Calcium/calmodulin ($Ca^{2+}/CaM$)-dependent protein phosphorylation has been implicated in various cellular processes, yet little is known about $Ca^{2+}/CaM$-dependent protein kinases (CaMKs) in plants. From an Arabidopsis expression library screen using a horseradish peroxidase-conjugated soybean calmodulin isoform (SCaM-1) as a probe, we isolated a full-length cDNA clone that encodes AtCK (Arabidopsis thaliana calcium/calmodulin-dependent protein kinase). The predicted structure of AtCK contains a serine/threonine protein kinase catalytic domain followed by a putative calmodulin-binding domain and a putative $Ca^{2+}$-binding domain. Recombinant AtCK was expressed in E. coli and bound to calmodulin in a $Ca^{2+}$-dependent manner. The ability of CaM to bind to AtCK was confirmed by gel mobility shift and competition assays. AtCK exhibited its highest levels of autophosphorylation in the presence of 3 mM $Mn^{2+}$. The phosphorylation of myelin basic protein (MBP) by AtCK was enhanced when AtCK was under the control of calcium-bound CaM, as previously observed for other $Ca^{2+}/CaM$-dependent protein kinases. In contrast to maize and tobacco CCaMKs (calcium and $Ca^{2+}/CaM$-dependent protein kinase), increasing the concentration of calmodulin to more than $3{\mu}M$ suppressed the phosphorylation activity of AtCK. Taken together our results indicate that AtCK is a novel Arabidopsis $Ca^{2+}/CaM$-dependent protein kinase which is presumably involved in CaM-mediated signaling.

Influence of Sustain Electrode Gap on Excited Xenon Atom in the Metastable State by Laser Absorption Spectroscopy in AC PDP (AC PDP에서 레이저 흡수법을 이용한 유지전극의 위치에 따른 제논 여기종 원자의 밀도 측정)

  • Lee, J.H.;Lim, J.E.;Lee, H.J.;Son, C.G.;Jeong, S.H.;Lee, S.B.;Yoo, N.L.;Han, Y.G.;Oh, P.Y.;Moon, M.W.;Ko, B.D.;Jeoung, J.M.;Moon, H.S.;Park, K.D.;Ahn, J.C.;Hong, J.W.;Cho, G.S.;Choi, E.H.
    • Proceedings of the Korean Institute of Electrical and Electronic Material Engineers Conference
    • /
    • 2005.05a
    • /
    • pp.131-134
    • /
    • 2005
  • PDP 방전 셀의 최적화 및 진공자외선 발광효율을 향상시키기 위한 목적으로 AC - PDP 미소방전에서 제논 여기종 원자의 밀도를 측정하는 레이저 흡수법을 개발하였다. 본 연구에서는 PDP 셀의 기체 압력을 350Torr, 제논 함량 10%로 고정하고, 전극 위에서의 여러 위치에서 준안정 준위 제논의 밀도를 흡수법으로 측정하였다. 실험 결과 제논 여기종의 밀도의 최대값은 전극의 위치(가장자리에서 안쪽으로의 거리)가 $50{\mu}m$, $120{\mu},\;150{\mu}m$ 일 때 $3.5{\times}10^{12}cm^{-3}$, $2.8{\times}10^{12}cm^{-3}$, $2.2{\times}10^{12}cm^{-3}$로 나타났다.

  • PDF

Flora of a Cool Temperate Forest Around Restoration Center for Endangered Species, Yeongyang

  • Kim, Seongjun;Lee, Chang-Woo;Park, Hwan-Joon;Lee, Byoung-Doo;Hwang, Jung Eun;An, Jiae;Park, Hyung Bin;Baek, Ju Hyeong;Kim, Pyoung Beom;Kim, Nam Young
    • Proceedings of the National Institute of Ecology of the Republic of Korea
    • /
    • v.2 no.1
    • /
    • pp.70-75
    • /
    • 2021
  • The present study aimed to clarify flora living at the area of Restoration Center for Endangered Species in Yeongyang, Gyeongbuk Province. In May, August, and September 2019 and in May and July 2020, all of vascular plants were recorded, and endangered, Korea endemic, and exotic plant species were further identified. The study site contained a total of 418 floral taxa (98 families, 261 genera, 384 species, 4 subspecies, 27 variations, and 3 formations), in which Magnoliophyta accounted for larger proportion (95.2%) than Pteridophyta (3.6%) and Pinophyta (1.2%). In addition, 1 endangered (Cypripedium macranthos Sw.) and 5 Korea endemic species (Aconitum pseudolaeve Nakai, Eleutherococcus divaricatus var. chiisanensis [Nakai] C.H. Kim & B.-Y. Sun, Lonicera subsessilis Rehder, Paulownia coreana Uyeki, and Weigela subsessilis [Nakai] L.H. Bailey) were detected. The number of exotic species was 33, consisting of 4 invasive-exotic, 4 potentially invasive-exotic, and 25 non-invasive species. Compared to a previous assessment before the establishment of the center (in 2014), there were increases in total floral taxa (from 361 to 418), endangered species (from 0 to 1), and exotic species (from 26 to 33). These results possibly reflect temporal changes in floral community, which should be confirmed through subsequent long term monitoring.