Biology subjects

Choi, B. H.

Publications and source records attributed to Choi, B. H..

4 recordsLinked to original sources

bioRxiv2026

Blockade of Kv3.1 by MK-801, a PCP-Derivative NMDA Receptor Inhibitor: Implications for Models of Schizophrenia

MK-801, a phencyclidine (PCP) derivative also known as dizocilpine, is a potent noncompetitive antagonist of the N-Methyl-D-aspartate receptor (NMDAr). The NMDAr plays a critical role in mediating excitatory synaptic transmission in the central nervous system (CNS) and is important in regulating synaptic plasticity, learning, and memory. MK-801 is known to induce schizophrenia-like phenotypes in animal models by blocking the NMDAr. Several studies have reported that the cognitive impairment associated with schizophrenia is linked to functional defects of ion channels in parvalbumin-positive GABAergic interneurons. Kv3.1 is a voltage-gated K+ (Kv) channel involved in the rapid repolarization of the action potential in neurons; it is richly expressed in parvalbumin-positive GABAergic interneurons and is associated with fast, repetitive spike generation. A decrease of Kv3.1 in the CNS has been reported to be associated with schizophrenia. In the present study, the effect of MK-801 on Kv3.1 was investigated using the whole-cell patch-clamp technique in Chinese hamster ovary (CHO) cells stably expressing Kv3.1. MK-801 caused a concentration-dependent inhibition of Kv3.1, with an IC50 of 10.81 M and a Hill coefficient of 0.89. The blocking potency was stronger at depolarized potentials, indicating a voltage-dependent block. MK-801 also produced a use-dependent block, inducing progressive inhibition with repeated stimulation at increased frequencies (1 Hz and 2 Hz), consistent with a delay in recovery from inactivation of Kv3.1 in the presence of MK-801. In addition, MK-801 induced a hyperpolarizing shift in the voltage dependence of the steady-state inactivation curve of Kv3.1. Taken together, these results indicate that MK-801 blocks Kv3.1 expressed in CHO cells in a concentration-, voltage-, and state-dependent manner. Given the importance of Kv3.1 in parvalbumin-positive, fast-spiking GABAergic interneurons, these findings suggest that MK-801 may alter the firing patterns of these inhibitory neurons, contributing to the onset and symptoms of schizophrenia.

pharmacology and toxicology↗

bioRxiv2023

Intermolecular interactions between cysteine and aromatic amino acids with phenyl moiety in the DNA-binding domain of heat shock factor 1 regulate thermal stress-induced trimerization.

In this study, we investigated the trimerization mechanism and structure of heat shock factor 1 (HSF1) in humans, goldfish, and walleye pollock at various temperatures. The trimerization of HSF1s were confirmed using western blotting using their respective antibodies. First, we examined the HSF1 DNA-binding domains of human (Homo sapiens), goldfish (Carassius auratus), and walleye pollock (Gadus chalcogrammus) by mutating key residues (36 and 103) that are thought to directly affect trimer generation. Humans, goldfish, and walleye pollock contain cysteine at residue 36, but cysteine (C), tyrosine (Y), and phenylalanine (F) at residue 103. Also, the trimer formation temperature of each species was found to be 42, 37, and 20 {degrees}C, respectively. In the mutation experiment, trimerization formed at 42 {degrees}C when residue 103 was C, at 37 {degrees}C it was Y, and at 20 {degrees}C it was F, regardless of the species. In addition, it was confirmed that when residue 103 of the three species was mutated to alanine (A), trimer was not formed. This suggest that, in addition to the previously identified C-C disulfide bonds in humans, C forms a trimer with a new type of bond with aromatic ring residues such as Y and F. Thus, HSF1 trimer formation temperature reveals the trimer creation mechanism through the fact that goldfish can have C-Y bonds at 37 {degrees}C, and walleye pollock can have C-F bonds at 20 {degrees}C. This study suggests that the trimer formation temperature and mechanism of HSF1 are regulated by the amino acid at residue 103.

biochemistry↗

bioRxiv2019

In vivo bioreactor using cellulose membrane benefit engineering cartilage by improving the chondrogenesis and modulating the immune response

To regenerate tissue engineered cartilage as a source for the restoration of cartilage defects, we used a human fetal cartilage progenitor cell (hFCPC) pellet for improve the chondrogenesis and modulation the immune response with a In vivo (IV) bioreactor system, that was buried subcutaneously in the host and then implanted into a cartilage defect. In vivo bioreactor (IVB) was composed of silicone tube and cellulose nanopore-size membrane. FCPC pellets were first cultured in vitro for 3 days, and then cultured in vitro, subcutaneous and IV bioreactor for 3 weeks. First evaluated the IV bioreactor fluid appearance, component and liquidity, and then evaluate chondrogenesis and immunogenicity of the pellets using gross observation, cell viability, histology, biochemical analysis, RT-PCR, and Western Blot, finally evaluates the cartilage repair and synovial inflammation using histology. The fluid color and transparency of IV bioreactor were similar to synovial fluid (SF) and the component was also close to SF compared to the serum. IV bioreactor system not only promotes the synthesis of cartilage matrix and maintains cartilage phenotype, but also delays the occurrence of calcification compared with subcutaneous. A IV bioreactor, which has been predominantly adopted to study cell differentiation, was effective in preventing host immune rejection.

cell biology↗

bioRxiv2018

Development of three-dimensional articular cartilage construct using silica nano-patterned substrate

Current strategies for cartilage cell therapy are mostly based on the use of autologous chondrocytes or mesenchymal stem cells (MSCs). However, these cells have limitations of a small number of cells available and of low chondrogenic ability, respectively. Many studies now suggest that fetal stem cells are more plastic than adult stem cells and can therefore more efficiently differentiate into target tissues. This study introduces, efficiency chondrogenic differentiation of fetal cartilage-derived progenitor cells (FCPCs) to adult cells can be achieved using a three-dimensional (3D) spheroid culture method based on silica nanopatterning techniques. In evaluating the issue of silica nano-particle size (Diameter of 300, 750, 1200 nm), each particle size was coated into the well of a 6-well tissue culture plate. FCPCs (2 x 105 cells/well in 6-well plate) were seeded in each well with chondrogenic medium. In this studys, the 300 nm substrate that formed multi-spheroids and the 1200 nm substrate that showed spreading were due to the cell-cell adhesion force(via N-cadherin) and cell-substrate(via Integrin) force, the 750 nm substrate that formed the mass-aggregation can be interpreted as the result of cell monolayer formation through cell-substrate force followed by cell-cell contact force contraction. We conclude that our 3D spheroid culture system contributes to an optimization for efficient differentiation of FCPC, offers insight into the mechanism of efficient differentiation of engineered 3D culture system, and has promise for wide applications in regeneration medicine and drug discovery fields.

cell biology↗