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Jeun M.,National University of Singapore | Jeoung J.W.,Seoul National University | Moon S.,National University of Singapore | Kim Y.J.,Seoul National University | And 5 more authors.
Biomaterials | Year: 2011

Ocular neuroprotection induced by localized heat shock proteins (HSPs) has been paid considerable attention as an efficacious treatment modality for glaucoma. However, the current clinical approaches to induce HSPs in the retinal ganglion cells (RGCs) are limited due to undesirable side effects. Here, we present that the induction of HSPs by local magnetic hyperthermia using engineered superparamagnetic Mn0.5Zn0.5Fe2O4 nanoparticle agents (EMZF-SPNPAs) with a 5.5 nm mean particle size is promisingly feasible for a physiologically tolerable ocular neuroprotection modality. The sufficiently high specific absorption rate (SAR) (~256.4 W/g in an agar solution) achieved at the biologically safe range of applied AC magnetic field and frequency as well as the superior biocompatibility of EMZF-SPNPA, which were confirmed from both in-vitro and in-vivo animal pilot studies, allowing it to be considered as a potential localized HSPs agent. Furthermore, the successful demonstration of a newly designed infusion technique, which diffuses the EMZF-SPNPAs through the vitreous body to the retina in a rat eye, more strongly verified the promises of this biotechnical approach to the ocular neuroprotection modality in glaucoma clinics. © 2010 Elsevier Ltd.

Jo D.H.,Seoul National University | Kim J.H.,Seoul National University | Heo J.-I.,Ischemic Hypoxic Disease Institute | Kim J.H.,Ischemic Hypoxic Disease Institute | Cho C.-H.,Ischemic Hypoxic Disease Institute
Molecules and Cells | Year: 2013

The hyaloid vessel is a transient vascular network that nourishes the lens and the primary vitreous in the early developmental periods. In hyaloid vessels devoid of the support of astrocytes, we demonstrate that tight junction proteins, zonula occludens-1 and occludin, are regularly expressed at the junction of endothelial cells. To figure out the factor influencing the formation of tight junctions in hyaloid vessels, we further progress to investigate the interactions between endothelial cells and pericytes, two representative constituent cells in hyaloid vessels. Interestingly, endothelial cells interact with pericytes in the early postnatal periods and the interaction between two cell types provokes the up-regulation of transforming growth factor β1. Further in vitro experiments demonstrate that transforming growth factor β1 induces the activation of Smad2 and Smad3 and the formation of tight junction proteins. Taken together, in hyaloid vessels, pericytes seem to regulate the formation of tight junctions by the interaction with endothelial cells even without the support of astrocytes. Additionally, we suggest that the hyaloid vessel is a valuable system that can be utilized for the investigation of cell-cell interaction in the formation of tight junctions in developing vasculatures. © The Korean Society for Molecular and Cellular Biology. All rights reserved.

Kim T.W.,Ischemic Hypoxic Disease Institute | Kang B.-H.,Ischemic Hypoxic Disease Institute | Jang H.,Ischemic Hypoxic Disease Institute | Jang H.,Seoul National University | And 16 more authors.
Stem Cells | Year: 2015

For cells to exit from pluripotency and commit to a lineage, the circuitry of a core transcription factor (CTF) network must be extinguished in an orderly manner through epigenetic modifications. However, how this choreographed epigenetic remodeling at active embryonic stem cell (ESC) genes occurs during differentiation is poorly understood. In this study, we demonstrate that C-terminal binding protein 2 (Ctbp2) regulates nucleosome remodeling and deacetylation (NuRD)-mediated deacetylation of H3K27 and facilitates recruitment of polycomb repressive complex 2 (PRC2)-mediated H3K27me3 in active ESC genes for exit from pluripotency during differentiation. By genomewide analysis, we found that Ctbp2 resides in active ESC genes and co-occupies regions with ESC CTFs in undifferentiated ESCs. Furthermore, ablation of Ctbp2 effects inappropriate gene silencing in ESCs by sustaining high levels of H3K27ac and impeding H3K27me3 in active ESC genes, thereby sustaining ESC maintenance during differentiation. Thus, Ctbp2 preoccupies regions in active genes with the NuRD complex in undifferentiated ESCs that are directed toward H3K27me3 by PRC2 to induce stable silencing, which is pivotal for natural lineage commitment. Stem Cells 2015;33:2442-2455 C-terminal binding protein 2 modulates the deacetylation of H3K27 with NuRD and is required for PRC2-mediated H3K27me3 in active ESC genes for exit from pluripotency during ESC differentiation. © 2015 AlphaMed Press.

Park K.S.,Pohang University of Science and Technology | Park K.S.,Ischemic Hypoxic Disease Institute | Pang B.,Seoul National University | Park S.J.,Seoul National University | And 6 more authors.
Molecules and Cells | Year: 2011

Hematopoietic stem cells (HSCs) are used therapeutically for hematological diseases and may also serve as a source for nonhematopoietic tissue engineering in the future. In other cell types, ion channels have been investigated as potential targets for the regulation of proliferation and differentiation. However, the ion channels of HSCs remain elusive. Here, we functionally characterized the ion channels of CD34 + cells from human peripheral blood. Using fluorescence-activated cell sorting, we confirmed that the CD34 + cells also express CD45 and CD133. In the CD34 +/ CD45 +/CD133 high HSCs, RT-PCR of 58 ion channel mRNAs revealed the coexpression of Kv1.3, Kv7.1, Nav1.7, TASK2, TALK2, TWIK2, TRPC4, TRPC6, TRPM2, TRPM7, and TRPV2. Whole-cell patch clamp recordings identified voltage-gated K + currents (putatively Kv1.3), pH-sensitive TASK2-like background K + currents, ADP-ribose-activated TRPM2 currents, temperature-sensitive TRPV2-like currents, and diacylglycerol- analogue-activated TRPC6-like currents. Our results lend new insight into the physiological role of ion channels in HSCs, the specific implications of which require further investigation. ©2011 KSMCB.

Park S.J.,Seoul National University | Yoo H.Y.,Seoul National University | Kim H.J.,Seoul National University | Kim H.J.,Ischemic Hypoxic Disease Institute | And 4 more authors.
Korean Journal of Physiology and Pharmacology | Year: 2012

Hypoxic pulmonary vasoconstriction (HPV) is physiologically important response for preventing mismatching between ventilation and perfusion in lungs. The HPV of isolated pulmonary arteries (HPV-PA) usually require a partial pretone by thromboxane agonist (U46619). Because the HPV of ventilated/perfused lungs (HPV-lung) can be triggered without pretone conditioning, we suspected that a putative tissue factor might be responsible for the pretone of HPV. Here we investigated whether HPV can be also observed in precision-cut lung slices (PCLS) from rats. The HPV in PCLS also required partial contraction by U46619. In addition, K + channel blockers (4AP and TEA) required U46619-pretone to induce significant contraction of PA in PCLS. In contrast, the airways in PCLS showed reversible contraction in response to the K + channel blockers without pretone conditioning. Also, the airways showed no hypoxic constriction but a relaxation under the partial pretone by U46619. The airways in PCLS showed reliable, concentration-dependent contraction by metacholine (EC 50, ∼210 nM). In summary, the HPV in PCLS is more similar to isolated PA than V/P lungs. The metacholine-induced constriction of bronchioles suggested that the PLCS might be also useful for studying airway physiology in situ.

PubMed | Ischemic Hypoxic Disease Institute, Sungkyunkwan University and Seoul National University
Type: Journal Article | Journal: Stem cells (Dayton, Ohio) | Year: 2015

Pluripotent stem cells (PSCs) have distinct metabolic properties that support their metabolic and energetic needs and affect their stemness. In particular, high glycolysis is critical for the generation and maintenance of PSCs. However, it is unknown how PSCs maintain and acquire this metabolic signature. In this study, we found that core pluripotency factors regulate glycolysis directly by controlling the expression of glycolytic enzymes. Specifically, Oct4 directly governs Hk2 and Pkm2, which are important glycolytic enzymes that determine the rate of glycolytic flux. The overexpression of Hk2 and Pkm2 sustains high levels of glycolysis during embryonic stem cell (ESC) differentiation. Moreover, the maintenance of high glycolysis levels by Hk2 and Pkm2 overexpression hampers differentiation and preserves the pluripotency of ESCs in the absence of leukemia inhibitory factor. Overall, our study identifies a direct molecular connection between core pluripotency factors and ESC metabolic signatures and demonstrates the significance of metabolism in cell fate determination.

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