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1,065 results on '"Lee, Seok-Yong"'

23. Enhanced efficacy of glycoengineered rice cell‐produced trastuzumab.

Author

Shin, Jun‐Hye, Oh, Sera, Jang, Mi‐Hwa, Lee, Seok‐Yong, Min, Chanhong, Eu, Young‐Jae, Begum, Hilal, Kim, Jong‐Chan, Lee, Gap Ryol, Oh, Han‐Bin, Paul, Matthew J., Ma, Julian K.‐C., Gwak, Ho‐Shin, Youn, Hyewon, and Kim, Seong‐Ryong

Subjects
AMINO acid sequence, CANCER cell proliferation, CELL lines, RICE, CELL suspensions
Abstract

Summary: For several decades, a plant‐based expression system has been proposed as an alternative platform for the production of biopharmaceuticals including therapeutic monoclonal antibodies (mAbs), but the immunogenicity concerns associated with plant‐specific N‐glycans attached in plant‐based biopharmaceuticals has not been completely solved. To eliminate all plant‐specific N‐glycan structure, eight genes involved in plant‐specific N‐glycosylation were mutated in rice (Oryza sativa) using the CRISPR/Cas9 system. The glycoengineered cell lines, PhytoRice®, contained a predominant GnGn (G0) glycoform. The gene for codon‐optimized trastuzumab (TMab) was then introduced into PhytoRice® through Agrobacterium co‐cultivation. Selected cell lines were suspension cultured, and TMab secreted from cells was purified from the cultured media. The amino acid sequence of the TMab produced by PhytoRice® (P‐TMab) was identical to that of TMab. The inhibitory effect of P‐TMab on the proliferation of the BT‐474 cancer cell line was significantly enhanced at concentrations above 1 μg/mL (****P < 0.0001). P‐TMab bound to a FcγRIIIa variant, FcγRIIIa‐F158, more than 2.7 times more effectively than TMab. The ADCC efficacy of P‐TMab against Jurkat cells was 2.6 times higher than that of TMab in an in vitro ADCC assay. Furthermore, P‐TMab demonstrated efficient tumour uptake with less liver uptake compared to TMab in a xenograft assay using the BT‐474 mouse model. These results suggest that the glycoengineered PhytoRice® could be an alternative platform for mAb production compared to current CHO cells, and P‐TMab has a novel and enhanced efficacy compared to TMab. [ABSTRACT FROM AUTHOR]

Published
2024
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24. The mutated cytoplasmic fragile X messenger ribonucleoprotein 1 (FMR1)‐interacting protein 2 (CYFIP2 S968F) regulates cocaine‐induced reward behaviour and plasticity in the nucleus accumbens.

Author

Kim, Young‐Jung, Kim, Kyungin, Lee, Youyoung, Min, Hee‐Won, Ko, Yong‐Hyun, Lee, Bo‐Ram, Hur, Kwang‐Hyun, Kim, Seon‐Kyung, Lee, Seok‐Yong, and Jang, Choon‐Gon

Subjects
NUCLEUS accumbens, PREFRONTAL cortex, PROTEIN expression, SENSITIZATION (Neuropsychology), COCAINE
Abstract

Background and Purpose: Cytoplasmic fragile X messenger ribonucleoprotein 1 (FMR1)‐interacting protein 2 (CYFIP2), as a component of the Wiskott–Aldrich syndrome protein family verprolin‐homologous protein (WAVE) regulatory complex, is involved in actin polymerization, contributing to neuronal development and structural plasticity. Mutating serine‐968 to phenylalanine (S968F) in CYFIP2 causes an altered cocaine response in mice. The neuronal mechanisms underlying this response remain unknown. Experimental Approach: We performed cocaine reward‐related behavioural tests and examined changes in synaptic protein phenotypes and neuronal morphology in the nucleus accumbens (NAc), using CYFIP2 S968F knock‐in mice to investigate the role of CYFIP2 in regulating cocaine reward. Key Results: CYFIP2 S968F mutation attenuated cocaine‐induced behavioural sensitization and conditioned place preference. Cocaine‐induced c‐Fos was not observed in the NAc of CYFIP2 S968F knock‐in mice. However, c‐Fos induction was still evident in the medial prefrontal cortex (mPFC). CYFIP2 S968F mutation altered cocaine‐associated CYFIP2 signalling, glutamatergic protein expression and synaptic density in the NAc following cocaine exposure. To further determine the role of CYFIP2 in NAc neuronal activity and the mPFC projecting to the NAc activity‐mediating reward response, we used optogenetic tools to stimulate the NAc or mPFC‐NAc pathway and observed that optogenetic activation of the NAc or mPFC‐NAc pathway induced reward‐related behaviours. This effect was not observed in the S968F mutation in CYFIP2. Conclusion and Implications: These results suggest that CYFIP2 plays a role in controlling cocaine‐mediated neuronal function and structural plasticity in the NAc, and that CYFIP2 could serve as a target for regulating cocaine reward. [ABSTRACT FROM AUTHOR]

Published
2024
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35. The ion channel TRPA1 is a modulator of the cocaine reward circuit in the nucleus accumbens

Author

Kim, Young-Jung, Choi, Su Jeong, Hong, Sa-Ik, Park, Jung-Cheol, Lee, Youyoung, Ma, Shi-Xun, Hur, Kwang-Hyun, Lee, Young, Kim, Kyeong-Man, Kim, Hyung Kyu, Kim, Hee Young, Lee, Seok-Yong, Choi, Se-Young, and Jang, Choon-Gon

Abstract

Drug addiction therapies commonly fail because continued drug use promotes the release of excessive and pleasurable dopamine levels. Because the connection between pleasure and drug use becomes hard-wired in the nucleus accumbens (NAc), which interfaces motivation, effective therapies need to modulate this mesolimbic reward system. Here, we report that mice with knockdown of the cation channel TRPA1 (transient receptor potential ankyrin 1) were resistant to the drug-seeking behavior and reward effects of cocaine compared to their wildtype litter mates. In our study, we demonstrate that TRPA1 inhibition in the NAc reduces cocaine activity and dopamine release, and conversely, that TRPA1 is critical for cocaine-induced synaptic strength in dopamine receptor 1-expressing medium spiny neurons. Taken together, our data support that cocaine-induced reward-related behavior and synaptic release of dopamine in the NAc are controlled by TRPA1 and suggest that TRPA1 has therapeutic potential as a target for drug misuse therapies.

Published
2024
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39. Transient receptor potential ankyrin 1 channel modulates the abuse‐related mechanisms of methamphetamine through interaction with dopamine transporter.

Author

Hur, Kwang‐Hyun, Lee, Youyoung, Donio, Audrey Lynn, Kim, Seon‐Kyung, Lee, Bo‐Ram, Seo, Jee‐Yeon, Kundu, Dooti, Kim, Kyeong‐Man, Kohut, Stephen J., Lee, Seok‐Yong, and Jang, Choon‐Gon

Subjects
METHAMPHETAMINE, DOPAMINE receptors, KNOCKOUT mice, DOPAMINE, NEURAL transmission, IMMUNOPRECIPITATION
Abstract

Background and Purpose: Methamphetamine (METH) use disorder has risen dramatically over the past decade, and there are currently no FDA‐approved medications due, in part, to gaps in our understanding of the pharmacological mechanisms related to METH action in the brain. Experimental Approach: Here, we investigated whether transient receptor potential ankyrin 1 (TRPA1) mediates each of several METH abuse‐related behaviours in rodents: self‐administration, drug‐primed reinstatement, acquisition of conditioned place preference, and hyperlocomotion. Additionally, METH‐induced molecular (i.e., neurotransmitter and protein) changes in the brain were compared between wild‐type and TRPA1 knock‐out mice. Finally, the relationship between TRPA1 and the dopamine transporter was investigated through immunoprecipitation and dopamine reuptake assays. Key Results: TRPA1 antagonism blunted METH self‐administration and drug‐primed reinstatement of METH‐seeking behaviour. Further, development of METH‐induced conditioned place preference and hyperlocomotion were inhibited by TRPA1 antagonist treatment, effects that were not observed in TRPA1 knock‐out mice. Similarly, molecular studies revealed METH‐induced increases in dopamine levels and expression of dopamine system‐related proteins in wild‐type, but not in TRPA1 knock‐out mice. Furthermore, pharmacological blockade of TRPA1 receptors reduced the interaction between TRPA1 and the dopamine transporter, thereby increasing dopamine reuptake activity by the transporter. Conclusion and Implications: This study demonstrates that TRPA1 is involved in the abuse‐related behavioural effects of METH, potentially through its modulatory role in METH‐induced activation of dopaminergic neurotransmission. Taken together, these data suggest that TRPA1 may be a novel therapeutic target for treating METH use disorder. [ABSTRACT FROM AUTHOR]

Published
2024
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