Intriguing Indium-salen Complexes as Multicolor Luminophores

Lee, Seon Hee,Shin, Nara,Kwak, Sang Woo,Hyun, Kyunglim,Woo, Won Hee,Lee, Ji Hye,Hwang, Hyonseok,Kim, Min,Lee, Junseong,Kim, Youngjo,Lee, Kang Mun,Park, Myung Hwan American Chemical Society 2017 Inorganic Chemistry Vol.56 No.5

<P>The series of novel salen-based indium complexes (3-Bu-t-S-R-salen)In-Me (3-Bu-t-S-R-salen = N,N'-bis(2-oxy-3-tert-butyl-S-R-salicylidene)-1,2-diarninoethane, R = H (1), Bu-t (2), Br (3), Ph (4), OMe (5), NMe2 (6)) and [(3-Bu-t-5-NMe3-salen)In-Me] (OTO)(2) (7; OTf = CF3SO3-) have been synthesized and fully characterized by NMR spectroscopy and elemental analysis. All indium complexes 1-7 are highly stable in air and even aqueous solutions. The solid-state structures for 3-5, which were confirmed by single-crystal X-ray analysis, exhibit square-pyramidal geometries around the indium center. Both the UV/vis absorption and PL spectra of 1-7 exhibit significant intramolecular charge transfer (ICT) transitions based on the salen moieties with systematically bathochromic shifts, which depend on the introduction of various kinds of substituents. Consequently, the emission spectra of these complexes cover almost the entire-visible region lambda(em)= 455-622 run).</P>

Genomic alteration before and after progression on first exposure to PARP inhibitor (PARPi) among ovarian cancer patients undergoing PARPi re-treatment

( Kyunglim Lee ),( Yoo-na Kim ),( Yong Jae Lee ),( Jung-yun Lee ),( Eun Ji Nam ),( Sang Wun Kim ),( Sunghoon Kim ),( Young Tae Kim ) 대한산부인과학회 2022 대한산부인과학회 학술대회 Vol.108 No.-

Objective: PARP inhibitor (PARPi) has become a standard of care in ovarian cancer, yet the genomic changes during PARPi is unknown. Thus, We analyzed matched tissue samples before and after progression on first exposure to PARPi among patients undergoing re-treatment with PARPi to understand the genomic changes, potential implication in resistance mechanism, and response to PARPi re-treatment. Methods: We identified 8 patients undergoing PARP re-treatment with matched tissue sample. Samples were sent to Foundation Medicine Inc, for the analysis of pathogenic short variants, copy number variants, loss of heterozygosity (LOH) and tumor mutational burden (TMB). Excluding 1 patient with QC failure of post sample due to low tumor content, 7 patients with matched tissue were analyzed. Relevant clinical information including progression-free survival of 1st PARPi and 2nd PARPi were collected. Results: The median duration of 1st PARPi was 5.5 months (range: 1 to 20). Based on the samples before 1st PARPi, the median LOH score was 24.85 (range: 10.9 to 34.2) and TMB was 3 mutations/Mb (range: 3 to 9). After progression on 1st PARPi, and prior to the start of 2nd PARPi, the median LOH was 27.9 (range: 22 to 42.4) and TMB was 9 mutations/Mb (range: 3 to 14). Various post-specific mutations were identified based on matched samples. Furthermore, LOH score increased in 5 patients (71.4%) and TMB increased in 4 patients (57.1%). The re-treatment duration was short for most patients, with a median of 2 months (range: 0.5 to 6), and in these patients oncogene amplifications were frequently observed. One patient used 2nd PARPi for a considerable period, 6 months. This patient had post-specific NF1 deletion, a tumor suppressor gene and loss of which is associated with treatment resistance in ovarian cancer. Conclusion: In ovarian cancer, post-specific mutations occur and LOH and TMB increase upon progression with PARPi. Further research on resistance mechanism in case of recurrence using PARPi is needed.

Neuroprotective effect of Cu,Zn-superoxide dismutase fused to a TCTP-derived protein transduction domain

Lee, Jisun,Kim, Sabin,Shin, Dong Hae,Kim, Hwa-Jung,Lee, Kyunglim Elsevier 2011 european journal of pharmacology Vol.666 No.1

<P><B>Abstract</B></P><P>Previously, we have reported that a 10-amino acid peptide (MIIYRDLISH) derived from the NH<SUB>2</SUB>-terminus of the human translationally controlled tumor protein (TCTP) functions as a protein transduction domain (PTD). In this study, we evaluated the transduction ability of SOD fused to TCTP-PTD (TCTP-SOD) into various cell lines. We also evaluated its ability to protect cells against paraquat-induced cell damage, in vitro and its neuroprotective effect in vivo against kainic acid-induced neuronal damage in an animal model. TCTP-SOD was transduced into various cell lines in a dose- and time-dependent manner without cytotoxic effect. Furthermore, TCTP-SOD showed cytoprotective activity in SH-SY5Y cells, and intraperitoneally, injected TCTP-SOD was delivered into the mouse brain and protected the cells in the hippocampal region against the damage induced by kainic acid. We propose TCTP-SOD as a potential candidate drug for treatment of brain diseases.</P>

Interaction of IgE-dependent Histamine-Releasing Factor with Na,K-ATPase triggers Histamine Release through the IgE-dependent Generation of Reactive Oxygen Species

Lee, Kyunglim 이화여자대학교 세포신호전달연구센터 2001 고사리 세포신호전달 심포지움 Vol. No.3

We searched for the regulatory proteins that interact with the 3rd cytoplasmic domain(CD3) of Na,K-ATPase using the yeast two-hybrid system and isolated cDNAs encoding IgE-dependent histamine-releasing factor(HRF). HRF was found to cause histamine release from IgE+ basophils of chronic allergic patients by an unknown mechanism. Here we show that exogenous HRF binds to the CD3 of Na,K-ATPase by crossing the plasma membrane of RBL-2H3 cells and acting as a cytoplasmic repressor of Na,K-ATPase to induce an initial increase of intracellular Ca2+, regardless of the presence of IgE. However, HRF generates reactive oxygen species(ROS) only in the presence of IgE, which in turn, increases Ca2+ influx, thereby inducing the histamine release. Thus our study indicates that the CD3 of Na,K-ATPase and ROS are pharmacological targets for the modulation of histamine release exerted by HRF.

Structural Characterization of Growth-Related Translationally Controlled Tumor Protein P23

Lee, Bong-Jin,Hong, Yoon-Hun,Park, Sang-Ho,Lee, Kyunglim Korean Magnetic Resonance Society 2001 Journal of the Korean Magnetic Resonance Society Vol.5 No.1

P23, a translationally controlled turner protein is involved in the interleukin-4 secretion from human basophils and is also known to be an IgE-dependent histamine-releasing factor. However, the precise physiological function and structure of P23 have not been elucidated. In the current study, we constructed the optimal expression and purification protocol of P23 and investigated the secondary structure and structural stability in various conditions. Circular dichroism (CD) investigation showed that the secondary structure of P23 adopts mainly a P-sheet conformation. CD spectroscopy and differential scanning calorimetry revealed that P23 is fairly stable in the pH range of neutral and mild-basic conditions and in the temperature range of 10 - 50$\^{C}$. Since the thermal stability and the P-sheet content of P23 were decreased by the addition of Ca$\^$2+/ ion, it could be suggested that Ca$\^$2+/ion induces structural change by partially destabilizing the structure of P23. In addition various H experiments were monitored to solve the aggregation of P23. Den results will provide the preliminary structural information about P23.

Cloning and Nucleotide Sequence of a cDNA Encoding the Rat Triosephosphate Isomerase

Lee, Kyunglim,Ryu, Jiwon 梨花女子大學校 藥學硏究所 1997 藥學硏究論文集 Vol.- No.6

A gene coding for triosephosphate isomerase (TPI) from a rat skeletal muscle cDNA library was cloned and its nucleotide sequence was determined. The 1,348-bp cDNA clone contains 24 bp 5' noncoding region, the entire 750 bp coding region corresponding to a protein of 249 amino acids, 547 bp 3' noncoding region and part of poly(A) tail. It also contains a polyadenylation signal, AATAAA, starting from 17 bp upstream of the poly(A) tail. The calculated molecular weight of rat TPI is 27.8 kDa and the net charge is +4. The deduced amino acid sequence from rat TPI cDNA sequence has 93% and 94% homology with that of mouse and human clones, respectively. The amino acids at the residue of Asn12, Lys14, His96, Glu166, His96, His101, Ala177, Tyr165, Glu130, Tyr209, and Ser212 in catalytic site are completely identical, confirming that the functional residues in TPI proteins are highly conserved throughout evolution. The most profound characteristic of rat TPI enzyme, compared with other TPIs, is that there are five cysteine substitution at the residue of 21, 27, 159, 195 and 204. A Glu123 instead of Gly was found in rabbit, rhesus, mouse and human sequences, Through the method of RT-PCR, the mRNA transcription level of TPI gene was found to be different among various tissues and was highest in muscle.

Studies on the Membrane Topology of the ( Na , K ) ATPase

Kyunglim Lee Yoon 생화학분자생물학회 1996 생화학분자생물학회 춘계학술발표논문집 Vol.- No.-

Interaction of the α subunit of Na,K-ATPase with cofilin

LEE, Kyunglim,JUNG, Jaehoon,KIM, Miyoung,GUIDOTTI, Guido 梨花女子大學校 藥學硏究所 2001 藥學硏究論文集 Vol.- No.10

The α1 subunit of rat Na,K-ATPase, composed of 1018 amino acids, is arranged in the membrane so that the middle third of the polypeptide forms a large cytoplasmic loop bordered on both sides by multiple transmenbrane segments. to identify proteins that might interact with the large cytoplasmic loop of Na,K-ATPase and potentially affect the function and/or the disposition of the pump in the cell, the yeast two-hybrid system was used to screen a rat skeletal muscle cDNA library. Several cDNA clones were isolated, some of which coded for coffilin, an actin-binding protein. Cofilin was co-immunoprecipitated with the αsubunit of Na,K-ATPase from extracts of COS-7 cells transiently transfected with haemagglutinin-epitope-tagged cofilin cDNA as well as from yeast extracts. By means of deletion analysis we showed. that the segment f cofilin between residues 45 and 99 is essential for functional association with the large cytoplasmic loop of Na,K-ATPase. Recombinant cofilin was shown to bind to the membrane-bound Na, K-APase; the association between the two proteins was demonstrated by confocal microscopy. The increased level of cofilin in transfected COS-7 cells caused an increase in the rate of ouabain-sensitive Rb^+ uptake, indicating that cofilin elicits, either directly or indirectly, enhanced Na, K-APase activity and that the interaction occurs in vivo.

IgE-Dependent Histamine-Releasing Factor as a Cytoplasmic Repressor of Na,K-ATPase

Lee, Kyunglim 이화여자대학교 세포신호전달연구센터 2000 고사리 세포신호전달 심포지움 Vol. No.2

The α subunit of rat (Na,K)ATPase contains the 3^(rd) large cytoplasmic loop(CL3) between H4 and H5 bordered on both sides by multiple transmembrane segments. To identify the proteins that might interact with the CL3 of (Na,K)ATPase and potentially affect the function of the pump in the cell, the yeast two-hybrid system was used to screen a rat skeletal muscle cDNA library. We found that IgE-dependent histamine-releasing factor(HRF), interacted with the CD3 of the α1, α2, and α3 isoform of (Na,K)ATPase, suggesting that the interaction is not isoform-specific. It. had been shown that IgE^(+) basophil released histamine when stimulated with HRF, although the mechanism by which HRF exerted its activity on the basophils was unknown. Here we show that the recombinant HRF is able to cross the plasma membrane of the RBL-2H3 of rat basophilic leukaemia cells and inhibits the (Na,K)ATPase activity in the absence and presence of IgE. Monitoring cytosolic Ca^(++) concentration with Ca^(++)-dye shows that HRF causes a rise in intracellular Ca^(++) in the absence and presence of IgE. However, the histamine degranulation occurs only in the presence of IgE, suggesting that the increase in intracellular Ca^(++) alone is insufficient to drive degranulation. The release was abolished by chelating the extracellular Ca^(++) and by benzamil, an inhibitor of Na,Ca-exchanger. Therefore, we suggest that the inhibition of the (Na,K)ATPase activity by HRF causes an increase in intracellular sodium which in turn allows exchanges of internal Na^(+) and external Ca^(++) via Na-Ca exchanger and leads to the IgE-mediated histamine release.

Cloning and Nucleotide Sequence of a cDNA Encoding the Rat Triosephosphate Isomerase

Lee, Kyunglim,Ryu, Jiwon The Pharmaceutical Society of Korea 1996 Archives of Pharmacal Research Vol.19 No.6

A gene coding for triosephosphate isomerase (TPI) from a rat skeletal muscle cDNA library was cloned and its nucleotide sequence was determined. The 1, 348-bp cDNA clone contains 24 bp $5^I$ noncoding region, the entire 750 bp coding region corresponding to a protein of 249 amino acids, $547bp 3^I$ noncoding region and part of a poly(A) tail. It also contains a polyadenylation signal, AATAAA, starting from 17 bp upstream of the poly(A) tail. The calculated molecular weight of rat TPI is 27.8 kDa and the net charge is +4. The deduced amino acid sequence from rat TPI CDNA sequence has 93% and 94% homology with that of mouse and human clones, respectively. The amino acids at the residue of Asn12, Lys14, His96, Glu 166, His96, His101, Ala177, Tyr165, Glu13O, Tyr2O9, and Ser212 in catalytic site are completely identical, confirming that the functional residues in TPI proteins are highly conserved throughout evolution. The most profound characteristic of rat TPI enzyme, compared with other TPIs, is that there are five cysteine substitutions at the residue of 21, 27, 159, 195 and 204. A Glu123 instead of Gly was found in rabbit, rhesus, mouse and human sequences. Through the method of RT-PCR, the mRNA transcription level of TPI gene was found to be different among various tissues and was highest in muscle.