Biomedical subjects

Hyojin Lee

Publications and source records attributed to Hyojin Lee.

7 recordsLinked to original sources

PubMed2006

Syntheses of hydroxy substituted 2-phenyl-naphthalenes as inhibitors of tyrosinase.

Oxyresveratrol and resveratrol, with hydroxy substituted trans-stilbene structure, exert potent inhibitory effects on cyclooxygenase, rat liver mitochondrial ATPase activity, and tyrosinase. As the isosteres of oxyresveratrol, a new family of hydroxyl substituted phenyl-naphthalenes were synthesized to show excellent inhibition of mushroom tyrosinase. Compound 10, which is isostere of resveratrol, showed IC50 value of 16.52 microM in mushroom tyrosinase activity. As compared to this, the reference compound, resveratrol, showed IC50 value of 55.61 microM. Compound 4, which is isostere of oxyresveratrol, showed IC50 value of 0.49 microM. Among the other three derivatives, compound 13 showed IC50 value of 0.034 microM.

Agaricales↗

PubMed2006

Transplanted dopamine neurons derived from primate ES cells preferentially innervate DARPP-32 striatal progenitors within the graft.

The correct identity and functional capacity of transplanted dopamine (DA) neurons derived in vitro from embryonic stem (ES) cells is a critical factor for the development of an ES cell-based replacement therapy for Parkinson's disease. We transplanted primate Cyno-1 ES cells differentiated in vitro for 4 (progenitor ES cells) or 6 (differentiated ES cells) weeks, or control fetal primate cells into the striatum of hemi-parkinsonian rats. Partial behavioral recovery in amphetamine-induced rotation was correlated with the number of ES-derived tyrosine hydroxylase-positive (TH+) neurons in the grafts (r=0.5, P<0.05). Post mortem analysis of ES-derived grafts revealed TH+neurons with mature morphology, similar to fetal DA neurons, and expression of midbrain transcription factors, such as Engrailed (En) and Nurr-1. While the total number of TH+neurons was not different between the two groups, TH/En co-expression was significantly higher (>90%) in grafts from differentiated ES cells than in grafts derived from progenitor cells (<50%), reflecting a more heterogeneous cellular composition. Within the grafts there was an overlap between ES-derived TH+axonal arbors and clusters of primate ES-derived striatal neurons expressing brain factor 1 (Bf-1, Foxg1) and DA and cAMP-regulated phosphoprotein (DARPP-32). Such overlap was never observed for other regional transcription factors that define neighboring forebrain domains in the developing brain, such as Nkx2.1 (medial ganglionic eminence), Nkx2.2 (pallidal and diencephalic progenitors) or Pax6 (dorsal telencephalic progenitors). Despite the heterogeneity of ES-derived graft cell composition, these results demonstrate normal phenotypic specification, conserved natural axonal target selectivity and functionality of DA neurons derived from primate ES cells.

Animals↗

PubMed2005

Surface-stabilized amorphous germanium nanoparticles for lithium-storage material.

Amorphous Ge nanoparticles with the particle size of approximately 10 nm were prepared by capping butyl groups and were characterized using XAS, TEM, FT-IR reflectance, and electrochemical cycling. The XAS results for the first-cycle Ge nanoparticles exhibited either a little particle aggregation after reformation of the Ge-Ge metallic bond or reformation of Ge-Ge metallic bond followed by a little particle aggregation. More interestingly, butyl groups, being electrochemically stable, remained after cycling, and the quantum mechanical calculation of the thermodynamic energy of the reaction using the GAMESS (General Atomic and Molecular Electronic Structure System) program suggested the formation of a very stable surface Ge-C bond that cannot be easily subjected to the subsequent chemical reactions. Initial charge capacity is 1470 mAh/g with an irreversible capacity ratio of 12%; no capacity fading was observed out to 30 cycles. Even at 5 C rate discharging, capacity retention was 98%, compared to that at 0.2 C rate discharging. In addition, the capacity was fully recovered at 0.2 C rate cycling.

Journal Article↗

PubMed2005

Long-term survival of dopamine neurons derived from parthenogenetic primate embryonic stem cells (cyno-1) after transplantation.

Dopamine (DA) neurons can be derived from human and primate embryonic stem (ES) cells in vitro. An ES cell-based replacement therapy for patients with Parkinson's disease requires that in vitro-generated neurons maintain their phenotype in vivo. Other critical issues relate to their proliferative capacity and risk of tumor formation, and the capability of migration and integration in the adult mammalian brain. Neural induction was achieved by coculture of primate parthenogenetic ES cells (Cyno-1) with stromal cells, followed by sequential exposure to midbrain patterning and differentiation factors to favor DA phenotypic specification. Differentiated ES cells were treated with mitomycin C and transplanted into adult immunosuppressed rodents and into a primate (allograft) with out immunosuppression. A small percentage of DA neurons survived in both rodent and primate hosts for the entire term of the study (4 and 7 months, respectively). Other neuronal and glial populations derived from Cyno-1 ES cells showed, in vivo, phenotypic characteristics and growth and migration patterns similar to fetal primate transplants, and a majority of cells (>80%) expressed the forebrain transcription factor brain factor 1. No teratoma formation was observed. In this study, we demonstrate long-term survival of DA neurons obtained in vitro from primate ES cells. Optimization of differentiation, cell selection, and cell transfer is required for functional studies of ES-derived DA neurons for future therapeutic applications.

Animals↗

PubMed2003

Neural subtype specification of fertilization and nuclear transfer embryonic stem cells and application in parkinsonian mice.

Existing protocols for the neural differentiation of mouse embryonic stem (ES) cells require extended in vitro culture, yield variable differentiation results or are limited to the generation of selected neural subtypes. Here we provide a set of coculture conditions that allows rapid and efficient derivation of most central nervous system phenotypes. The fate of both fertilization- and nuclear transfer-derived ES (ntES) cells was directed selectively into neural stem cells, astrocytes, oligodendrocytes or neurons. Specific differentiation into gamma-aminobutyric acid (GABA), dopamine, serotonin or motor neurons was achieved by defining conditions to induce forebrain, midbrain, hindbrain and spinal cord identity. Neuronal function of ES cell-derived dopaminergic neurons was shown in vitro by electron microscopy, measurement of neurotransmitter release and intracellular recording. Furthermore, transplantation of ES and ntES cell-derived dopaminergic neurons corrected the phenotype of a mouse model of Parkinson disease, demonstrating an in vivo application of therapeutic cloning in neural disease.

Animals↗

PubMed2002

Role of ATP-binding motifs on DNA-binding activity and biological function of Rhp51, a Rad51 homologue in fission yeast.

Rhp51, a RecA and Rad51 homologue of Schizosaccharomyces pombe, plays a pivotal role in homologous recombination and recombinational repair. It has a set of the well-conserved type A and type B ATP-binding motifs, which are highly conserved in all RecA homologues. In a previous study [Kim, Lee, Park, Park and Park (2001) Nucleic Acids Res. 29, 1724-1732], we reported that a single mutation of the conserved lysine in A motif [Lys(155)-->Ala (K155A)] destroyed the DNA repair ability of Rhp51 and that overexpression of this mutant protein conferred dominant negativity. In the present paper, we investigated DNA-binding properties of recombinant Rhp51 and its mutant proteins. Purified Rhp51 protein showed ATP-dependent double- and single-strand DNA-binding activities. To characterize the role of ATP-binding motifs, we generated Rhp51 K155A and Rhp51 Asp(244)-->Gln (D244Q), which have a single amino acid substitution in A and B motifs respectively. Interestingly, K155A and D244Q mutations impaired ATP-dependent DNA binding in a different manner. K155A lost the DNA binding itself, whereas D244Q maintained the binding ability but lost the ATP dependency. However, despite the difference in DNA-binding ability, both mutations failed to rescue the methylmethane sulphonate and UV sensitivity of the rhp51Delta mutant. Together, these results suggested that not only the DNA binding but also the ATP dependence in DNA binding is required for proper in vivo functioning of Rhp51.

Adenosine Triphosphate↗

PubMed2002

Physical interaction between recombinational proteins Rhp51 and Rad22 in Schizosaccharomyces pombe.

In eukaryotes, Rad51 and Rad52 are two key components of homologous recombination and recombinational repair. These two proteins interact with each other. Here we investigated the role of interaction between Rhp51 and Rad22, the fission yeast homologs of Rad51 and Rad52, respectively, on the function of each protein. We identified a direct association between the two proteins and their self-interactions both in vivo and in vitro. We also determined the binding domains of each protein that mediate these interactions. To characterize the role of Rhp51-Rad22 interaction, we used random mutagenesis to identify the mutants Rhp51 and Rad22, which cannot interact each other. Interestingly, we found that mutant Rhp51 protein, which cannot interact with either Rad22 or Rti1 (G282D), lost its DNA repair ability. In contrast, mutant Rad22 proteins, which cannot specifically bind to Rhp51 (S379L and P381L), maintained their DNA repair ability. These results suggest that the interaction between Rhp51 and Rad22 is crucial for the recombinational repair function of Rhp51. However, the significance of this interaction on the function of Rad22 remains to be characterized further.

Amino Acid Sequence↗