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김광세,Yong-KilHong,YoonLee,Joo-YoungShin,Soo-IkChang,SooIlChung,YoungAeJoe 생화학분자생물학회 2003 Experimental and molecular medicine Vol.35 No.6
The serine protease urokinase-type plasminogen activator (uPA) is im plicated in pericellular proteolysis in a variety of physiological and pathological processes including angiogenesis and tumor metastasis. The kringle domain of uPA (UK1) has proven to be an anti-angiogenic molecule with unknown mechanism and amino terminal fragment of uPA (u-ATF) with additional growth factor-like domain can be used for blocking interaction of uPA and uPA receptor. Here, we compared anti-angiogenic activities of these two molecules in vitro and in vivo. The recombinant u-ATF from E. coli and refolded in vitro was found to bind to uPAR with high affinity, whereas E. coli-derived UK1 showed no binding by Biacore analysis. In contrast to UK1 having potent inhibitory effect, u-ATF exhibited low inhibitory effect on bovine capillary endothelial cell growth (ED50>320 nM). Furthermore, u-ATF inhibition of VEGF-induced migration of human umbilical vein endothelial cell was far less sensitive (IC50 = 600 nM) than those observed with UK1, and angiogenesis inhibition was marginal in chorioallantoic membrane. These results suggest that kringle domain alone is sufficient for potent antiangiogenic activity and additional growth factor-like domain diverts this molecule in undergoing different mechanism such as inhibition of uPA/uPAR interaction rather than undergoing distinct antiangiogenic mechanism driven by kringle domain.
Hur, Yeoun,Tae, Sookil,Koh, Yun-Joo,Hong, Sung-Hyun,Yoon, Young Ho,Jang, Haejong,Kim, Sooji,Kim, Kyeong Ho,Kang, Seung Woo,Lee, Youngshin,Han, Sang Beom Korean Society for Mass Spectrometry 2014 Mass spectrometry letters Vol.5 No.2
A specific and sensitive liquid chromatography-electrospray ionization tandem mass spectrometry method (LC-ESI-MS/MS) was developed and validated for the simultaneous quantification of porphyrins (coproporphyrin, pentacarboxylporphyrin, hexacarboxylporphyrin, heptacarboxylporphyrin, and uroporphyrin) in human plasma and urine. Acidified plasma samples and urine samples were prepared by using liquid-liquid extraction using ethyl acetate and protein precipitation with acetonitrile, respectively. The separation was achieved onto a Synergi Fusion RP column ($150mm{\times}2.0mm$, $4{\mu}m$) with a gradient elution of mobile phase A (0.1% formic acid in 2 mmol/L ammonium acetate, v/v) and mobile phase B (20% methanol in acetonitrile, v/v) at a flow rate of $450{\mu}L$/min. Porphyrins and the internal standard (IS), coproporphyrin I-$^{15}N_4$, were detected by a tandem mass spectrometer equipped with an electrospray ion source operating in positive ion mode. Multiple reaction monitoring (MRM) transitions of the protonated precursor ions and the related product ions were optimized to increase selectivity and sensitivity. The proposed method was validated by assessing selectivity, linearity, limit of quantification (LOQ), precision, accuracy, recovery, and stability. The calibration curves were obtained in the range of 0.1-100 nmol/L and the LOQs were estimated as 0.1 nmol/L for all porphyrins. Results obtained from the validation study of porphyrins showed good accuracy, precision, recovery, and stability. Finally, the proposed method was successfully applied to clinical studies on the autism spectrum disorder (ASD) diagnosis of 203 Korean children.
( Yeoun Hur ),( Sookil Tae ),( Yun Joo Koh ),( Sung Hyun Hong ),( Young Ho Yoon ),( Haejong Jang ),( Sooji Kim ),( Kyeong Ho Kim ),( Seung Woo Kang ),( Youngshin Lee ),( Sang Beom Han ) 한국질량분석학회 2014 Mass spectrometry letters Vol.5 No.2
A specific and sensitive liquid chromatography-electrospray ionization tandem mass spectrometry method (LC-ESIMS/ MS) was developed and validated for the simultaneous quantification of porphyrins (coproporphyrin, pentacarboxylporphyrin, hexacarboxylporphyrin, heptacarboxylporphyrin, and uroporphyrin) in human plasma and urine. Acidified plasma samples and urine samples were prepared by using liquid-liquid extraction using ethyl acetate and protein precipitation with acetonitrile, respectively. The separation was achieved onto a Synergi Fusion RP column (150 mm × 2.0 mm, 4 μm) with a gradient elution of mobile phase A (0.1% formic acid in 2 mmol/L ammonium acetate, v/v) and mobile phase B (20% methanol in acetonitrile, v/ v) at a flow rate of 450 μL/min. Porphyrins and the internal standard (IS), coproporphyrin I-15N4, were detected by a tandem mass spectrometer equipped with an electrospray ion source operating in positive ion mode. Multiple reaction monitoring (MRM) transitions of the protonated precursor ions and the related product ions were optimized to increase selectivity and sensitivity. The proposed method was validated by assessing selectivity, linearity, limit of quantification (LOQ), precision, accuracy, recovery, and stability. The calibration curves were obtained in the range of 0.1-100 nmol/L and the LOQs were estimated as 0.1 nmol/L for all porphyrins. Results obtained from the validation study of porphyrins showed good accuracy, precision, recovery, and stability. Finally, the proposed method was successfully applied to clinical studies on the autism spectrum disorder (ASD) diagnosis of 203 Korean children.
Jong Yung Park,Suji Chae,Chang Seop Kim,Yoon Jae Kim,Hyun Joo Yi,Eunjoo Han,Youngshin Joo,Surim Hong,Jae Won Yun,Hyojung Kim,Kyung Ho Shin 대한약리학회 2019 The Korean Journal of Physiology & Pharmacology Vol.23 No.6
Nociceptin/orphanin FQ (N/OFQ) and its receptor, nociceptin opioid peptide (NOP) receptor, are localized in brain areas implicated in depression including the amygdala, bed nucleus of the stria terminalis, habenula, and monoaminergic nuclei in the brain stem. N/OFQ inhibits neuronal excitability of monoaminergic neurons and monoamine release from their terminals by activation of G protein-coupled inwardly rectifying K+ channels and inhibition of voltage sensitive calcium channels, respectively. Therefore, NOP receptor antagonists have been proposed as a potential antidepressant. Indeed, mounting evidence shows that NOP receptor antagonists have antidepressant-like effects in various preclinical animal models of depression, and recent clinical studies again confirmed the idea that blockade of NOP receptor signaling could provide a novel strategy for the treatment of depression. In this review, we describe the pharmacological effects of N/OFQ in relation to depression and explore the possible mechanism of NOP receptor antagonists as potential antidepressants.
Park, Jong Yung,Chae, Suji,Kim, Chang Seop,Kim, Yoon Jae,Yi, Hyun Joo,Han, Eunjoo,Joo, Youngshin,Hong, Surim,Yun, Jae Won,Kim, Hyojung,Shin, Kyung Ho The Korean Society of Pharmacology 2019 The Korean Journal of Physiology & Pharmacology Vol.23 No.6
Nociceptin/orphanin FQ (N/OFQ) and its receptor, nociceptin opioid peptide (NOP) receptor, are localized in brain areas implicated in depression including the amygdala, bed nucleus of the stria terminalis, habenula, and monoaminergic nuclei in the brain stem. N/OFQ inhibits neuronal excitability of monoaminergic neurons and monoamine release from their terminals by activation of G protein-coupled inwardly rectifying $K^+$ channels and inhibition of voltage sensitive calcium channels, respectively. Therefore, NOP receptor antagonists have been proposed as a potential antidepressant. Indeed, mounting evidence shows that NOP receptor antagonists have antidepressant-like effects in various preclinical animal models of depression, and recent clinical studies again confirmed the idea that blockade of NOP receptor signaling could provide a novel strategy for the treatment of depression. In this review, we describe the pharmacological effects of N/OFQ in relation to depression and explore the possible mechanism of NOP receptor antagonists as potential antidepressants.