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Englerin A-sensing charged residues for transient receptor potential canonical 5 channel activation
SeungJoo Jeong,Juyeon Ko,Minji Kim,Ki Chul Park,Eunice Yon June Park,Jinsung Kim,Youngjoo Baik,Jinhong Wie,Art E,Cho,Ju-hong Jeon,Insuk So 대한약리학회 2019 The Korean Journal of Physiology & Pharmacology Vol.23 No.3
The transient receptor potential canonical (TRPC) 5 channel, known as a nonselective cation channel, has a crucial role in calcium influx. TRPC5 has been reported to be activated by muscarinic receptor activation and extracellular pH change and inhibited by the protein kinase C pathway. Recent studies have also suggested that TRPC5 is extracellularly activated by englerin A (EA), but the mechanism remains unclear. The purpose of this study is to identify the EA-interaction sites in TRPC5 and thereby clarify the mechanism of TRPC5 activation. TRPC5 channels are over-expressed in human embryonic kidney (HEK293) cells. TRPC5 mutants were generated by site-directed mutagenesis. The whole-cell patch-clamp configuration was used to record TRPC5 currents. Western analysis was also performed to observe the expression of TRPC5 mutants. To identify the EA-interaction site in TRPC5, we first generated pore mutants. When screening the mutants with EA, we observed the EA-induced current increases of TRPC5 abolished in K554N, H594N, and E598Q mutants. The current increases of other mutants were reduced in different levels. We also examined the functional intactness of the mutants that had no effect by EA with TRPC5 agonists, such as carbachol or GTPγS. Our results suggest that the three residues, Lys-554, His-594, and Glu-598, in TRPC5 might be responsible for direct interaction with EA, inducing the channel activation. We also suggest that although other pore residues are not critical, they could partly contribute to the EA-induced channel activation.
Englerin A-sensing charged residues for transient receptor potential canonical 5 channel activation
Jeong, SeungJoo,Ko, Juyeon,Kim, Minji,Park, Ki Chul,Park, Eunice Yon June,Kim, Jinsung,Baik, Youngjoo,Wie, Jinhong,Cho, Art E.,Jeon, Ju-hong,So, Insuk The Korean Society of Pharmacology 2019 The Korean Journal of Physiology & Pharmacology Vol.23 No.3
The transient receptor potential canonical (TRPC) 5 channel, known as a nonselective cation channel, has a crucial role in calcium influx. TRPC5 has been reported to be activated by muscarinic receptor activation and extracellular pH change and inhibited by the protein kinase C pathway. Recent studies have also suggested that TRPC5 is extracellularly activated by englerin A (EA), but the mechanism remains unclear. The purpose of this study is to identify the EA-interaction sites in TRPC5 and thereby clarify the mechanism of TRPC5 activation. TRPC5 channels are over-expressed in human embryonic kidney (HEK293) cells. TRPC5 mutants were generated by site-directed mutagenesis. The whole-cell patch-clamp configuration was used to record TRPC5 currents. Western analysis was also performed to observe the expression of TRPC5 mutants. To identify the EA-interaction site in TRPC5, we first generated pore mutants. When screening the mutants with EA, we observed the EA-induced current increases of TRPC5 abolished in K554N, H594N, and E598Q mutants. The current increases of other mutants were reduced in different levels. We also examined the functional intactness of the mutants that had no effect by EA with TRPC5 agonists, such as carbachol or $GTP{\gamma}S$. Our results suggest that the three residues, Lys-554, His-594, and Glu-598, in TRPC5 might be responsible for direct interaction with EA, inducing the channel activation. We also suggest that although other pore residues are not critical, they could partly contribute to the EA-induced channel activation.
Status of the Development of OECD Test Method Detecting EDCs
Hyeyeong Seo,Huiwon Seo,Seungjoo Baik,Yejin Kim,Ahreum Seo,Seok-Hee Lee,Nick Byrd,Yooheon Park 한국식품영양과학회 2021 한국식품영양과학회 학술대회발표집 Vol.2021 No.10
Endocrine Disrupting Chemicals (EDCs) are chemicals that interfere with endocrine function. These ‘disruptions’ can sometimes cause devastating problems such as attention deficit disorder, breast cancer, prostate cancer, thyroid cancer, feminizing men in men, or virilizing effects in women. Based on the need for the management of EDCs, the OECD Advisory Group on Endocrine Substance Testing and Evaluation discussed the development and update of test guidelines and related documents for Endocrine Substance Testing and Evaluation. Certain OECD test guidelines using laboratory animals already addressed toxicity to the hormonal system. However, with increasing awareness of animal welfare, the OECD strongly recommends supporting the development of non-animal test applicable to the screening and evaluation of EDCs. Various alternative animal test methods have been established as OECD-approved test methods (so called Test Guidelines), and Korea is also making great efforts. In this session, the OECD accreditation process and the current status of test method development will be discussed.
Yejin Kim,Seok-Hee Lee,Hyeyeong Seo,Huiwon Seo,Seungjoo Baik,Ahreum Seo,Yooheon Park 한국식품영양과학회 2021 한국식품영양과학회 학술대회발표집 Vol.2021 No.10
The skeletal system completes as the body grows, especially bone mass, which is mostly formed during puberty. Osteoporosis develops as lose the balance of bone formation and bone resorption processes due to the loss of bone mass. Therefore, it is very important to maintain the balance of bone formation and bone resorption processes and form ‘good-quality’ bones through proper nutrient intake from adolescence. In this study, it was confirmed whether organic whole milk powder (OWMP) and colostrum basic protein (CBP) were effective for skeletal growth. Individual effects and interaction effects of OWMP and CBP were confirmed in ovariectomzed rat model. The experimental diet was designed so that total calories, protein content, and fat-derived calories were even. CBP and OWMP were included in the diet at 0.1% and 10%, respectively. To confirm the skeletal growth efficacy of organic whole milk powder (OWMP) and colostrum protein (CBP), bone parameters were evaluated by microCT, and bone serum parameters were evaluated by measuring blood Ca and P concentrations. Osteoblast-osteoclast related factors in serum were also identified toi confirm the effect.
Ahreum Seo,Seok-Hee Lee,Hyeyeong Seo,Huiwon Seo,Seungjoo Baik,Yejin Kim,Yooheon Park 한국식품영양과학회 2021 한국식품영양과학회 학술대회발표집 Vol.2021 No.10
Biocide refers to a substance used to remove harmful organisms other than humans and animals, and non-agricultural pesticides, disinfectants, and disinfectants (preservatives, preservatives, antibacterial agents) have been used. Some biocidal chemicals bind to estrogen receptors to imitate, block, or inhibit the estrogen. In this study, we selected 13 substances, including Vinclozolin, Atrazine, and Ketoconazole, well-known as pesticides, among 78 chemicals that the ICCVAM recommended the possibility of endocrine activity in estrogen and androgen. To evaluate estrogenic activity, which is part of the AOP framework, we used the previously developed Bioluminescence Resonance Energy Transfer (BRET)-based Estrogen Dimerization Assay (DA) and OECD Transactivation Assay (TA, TG 455). As a result, one of the 13 chemicals of biocides did not form a dimer in the BRET based-estrogen DA but showed antagonism in the TA. This results not only provided scientific information on the toxicity pathways of biocide chemicals that have not been previously presented, but also suggested the need for research on pathways other than those affecting typically known estrogen receptor transactivation.
Kim, Taekhoon,Cho, Eun‐,Jin,Chae, Youngjoo,Kim, Minsik,Oh, Aram,Jin, Juhong,Lee, Eun‐,Sook,Baik, Hionsuck,Haam, Seungjoo,Suh, Jin‐,Suck,Huh, Yong‐,Min,Lee, Kwangyeol WILEY‐VCH Verlag 2011 Angewandte Chemie Vol.123 No.45
<P><B>Bildverstärkung</B>: Igelförmige MnO@Mn<SUB>3</SUB>O<SUB>4</SUB>‐Kern‐Schale‐Nanopartikel können durch anisotropes Ätzen hergestellt werden und eignen sich als pH‐aktivierbare <I>T</I><SUB>1</SUB>‐Kontrastmittel in der Kernspintomographie. Die aus der MnO‐Phase an Stellen in den Tumorzellen mit niedrigem pH‐Wert freigesetzten Manganionen erhöhen den <I>T</I><SUB>1</SUB>‐Kontrast der gesamten Tumormasse.</P>