A New Triggering Receptor Expressed on Myeloid Cells (TREM) Family Member, TLT-6, is Involved in Activation and Proliferation of Macrophages

원경종,박성원,이승훈,공일근,채정일,김보경,이은종,김동규 대한면역학회 2015 Immune Network Vol.15 No.5

The triggering receptor expressed on myeloid cells (TREM) family, which is abundantly expressed in myeloid lineage cells, plays a pivotal role in innate and adaptive immune response. In this study, we aimed to identify a novel receptor expressed on hematopoietic stem cells (HSCs) by using in silico bioinformatics and to characterize the identified receptor. We thus found the TREM-like transcript (TLT)-6, a new member of TREM family. TLT-6 has a single immunoglobulin domain in the extracellular region and a long cytoplasmic region containing 2 immunoreceptor tyrosine-based inhibitory motif-like domains. TLT-6 transcript was expressed in HSCs, monocytes and macrophages. TLT-6 protein was up-regulated on the surface of bone marrow-derived and peritoneal macrophages by lipopolysaccharide stimulation. TLT-6 exerted anti-proliferative effects in macrophages. Our results demonstrate that TLT-6 may regulate the activation and proliferation of macrophages.

Proteomic Analysis of Colonic Mucosal Tissue from Tuberculous and Ulcerative Colitis Patients

권성춘,원경종,Seoung Hyo Jung,이강파,Dong-Youb Lee,Eun-Seok Park,김보경,천갑진,한군희 대한약리학회 2012 The Korean Journal of Physiology & Pharmacology Vol.16 No.3

Changes in the expression profiles of specific proteins leads to serious human diseases, including colitis. The proteomic changes related to colitis and the differential expression between tuberculous (TC) and ulcerative colitis (UC) in colon tissue from colitis patients has not been defined. We therefore performed a proteomic analysis of human TC and UC mucosal tissue. Total protein was obtained from the colon mucosal tissue of normal, TC, and UC patients, and resolved by 2-dimensional electrophoresis (2-DE). The results were analyzed with PDQuest using silver staining. We used matrix-assisted laser desorption ionization time-of-flight/time-of-flight spectrometry (MALDI TOF/TOF) to identify proteins differentially expressed in TC and UC. Of the over 1,000 proteins isolated, three in TC tissue and two in UC tissue displayed altered expression when compared to normal tissue. Moreover, two proteins were differentially expressed in a comparative analysis between TC and UC. These were identified as mutant β-actin, α-enolase and Charcot-Leyden crystal protein. In particular, the expression of α- enolase was significantly greater in TC compared with normal tissue, but decreased in comparison to UC, implying that α-enolase may represent a biomarker for differential diagnosis of TC and UC. This study therefore provides a valuable resource for the molecular and diagnostic analysis of human colitis.

Increased HoxB4 Inhibits Apoptotic Cell Death in Pro-B Cells

박성원,원경종,이용수,김혜선,김유경,이현우,김보경,이병한,김진회,김동구 대한약리학회 2012 The Korean Journal of Physiology & Pharmacology Vol.16 No.4

HoxB4, a homeodomain-containing transcription factor, is involved in the expansion of hematopoietic stem cells and progenitor cells in vivo and in vitro, and plays a key role in regulating the balance between hematopoietic stem cell renewal and cell differentiation. However, the biological activity of HoxB4 in other cells has not been reported. In this study, we investigated the effect of overexpressed HoxB4 on cell survival under various conditions that induce death, using the Ba/F3 cell line. Analysis of phenotypical characteristics showed that HoxB4 overexpression in Ba/F3 cells reduced cell size, death, and proliferation rate. Moreover, the progression from early to late apoptotic stages was inhibited in Ba/F3 cells subjected to HoxB4 overexpression under removal of interleukin-3-mediated signal, leading to the induction of cell cycle arrest at the G2/M phase and attenuated cell death by Fas protein stimulation in vitro. Furthermore, apoptotic cell death induced by doxorubicin-treated G2/M phase cell-cycle arrest also decreased with HoxB4 overexpression in Ba/F3 cells. From these data, we suggest that HoxB4 may play an important role in the regulation of pro-B cell survival under various apoptotic death environments.

p38 MAPK Participates in Muscle-Specific RING Finger 1-Mediated Atrophy in Cast-Immobilized Rat Gastrocnemius Muscle

김정환,원경종,이환명,황병용,배영민,최완수,송혁,임기원,이창권,김보경 대한약리학회 2009 The Korean Journal of Physiology & Pharmacology Vol.13 No.6

Skeletal muscle atrophy is a common phenomenon during the prolonged muscle disuse caused by cast immobilization, extended aging states, bed rest, space flight, or other factors. However, the cellular mechanisms of the atrophic process are poorly understood. In this study, we investigated the involvement of mitogen-activated protein kinase (MAPK) in the expression of muscle-specific RING finger 1 (MuRF1) during atrophy of the rat gastrocnemius muscle. Histological analysis revealed that cast immobilization induced the atrophy of the gastrocnemius muscle, with diminution of muscle weight and cross-sectional area after 14 days. Cast immobilization significantly elevated the expression of MuRF1 and the phosphorylation of p38 MAPK. The starvation of L6 rat skeletal myoblasts under serum-free conditions induced the phosphorylation of p38 MAPK and the characteristics typical of cast-immobilized gastrocnemius muscle. The expression of MuRF1 was also elevated in serum-starved L6 myoblasts, but was significantly attenuated by SB203580, an inhibitor of p38 MAPK. Changes in the sizes of L6 myoblasts in response to starvation were also reversed by their transfection with MuRF1 small interfering RNA or treatment with SB203580. From these results, we suggest that the expression of MuRF1 in cast-immobilized atrophy is regulated by p38 MAPK in rat gastrocnemius muscles.

Olibanum Extract Inhibits Vascular Smooth Muscle Cell Migration and Proliferation in Response to Platelet-Derived Growth Factor

최옥병,박주훈,이예진,이창권,원경종,김정환,이환명,김보경 대한약리학회 2009 The Korean Journal of Physiology & Pharmacology Vol.13 No.2

Olibanum (Boswellia serrata) has been shown to have anti-inflammatory, anti-arthritic and anti- cancer effects. This study determined the role of a water extract of olibanum in platelet-derived growth factor (PDGF)-stimulated proliferation and migration of rat aortic smooth muscle cells (RASMCs). PDGF-BB induced the migration and proliferation of RASMCs that were inhibited by olibanum extract in a dose-dependent manner. The PDGF-BB-increased phosphorylation of p38 mitogen-activated protein kinase (MAPK); the heat shock protein (Hsp) 27 was significantly inhibited by the olibanum extract. The effects of PDGF-BB-induced extracellular signal-regulated kinase1/2 was not altered by the olibanum extract. Treatment with olibanum extract inhibited PDGF-BB-stimulated sprout out growth of aortic rings. These results suggest that the water extract of olibanum inhibits PDGF-BB-stimulated migration and proliferation in RASMCs as well as sprout out growth, which may be mediated by the inhibition of the p38 MAPK and Hsp27 pathways.

Phorbol Ester-induced Contraction Through p38 Mitogen-activated Protein Kinase is Diminished in Aortas from DOCA-Salt Hypertensive Rats

Chang-Kwon Lee,Junghwan Kim,원경종,Hwan Myung Lee,Hyo Jin Kim,Hui Yul Roh,Hyo-Jun Park,신화섭,박태규,Bokyung Kim,이상목 대한약학회 2006 Archives of Pharmacal Research Vol.29 No.11

The role of mitogen-activated protein kinase (MAPK) in the decreased contractile response to phorbol ester in aortic smooth muscle strips from deoxycorticosterone acetate (DOCA)-salt hypertensive rats was examined. Norepinephrine (NE) evoked greater contractility in aortic strips from DOCA rats than in those of sham-operated rats. 12-Deoxyphorbol 13-isobutyrate (DPB) induced contraction in Ca2+-free medium, which was diminished in strips from DOCA rats compared to sham-operated rats. Vasoconstrictions induced by these stimulants were inhibited by SB203580 and PD098059, inhibitors of p38 MAPK and extracellular signalregulated kinase (ERK) 1/2, respectively, in both strips. The phosphorylation of p38 MAPK and ERK1/2 induced by NE was greater in strips from DOCA rats compared to those from shamoperated rats, and this phosphorylation was inhibited by the kinase inhibitors. DPB increased the phosphorylation of p38 MAPK and ERK1/2 in strips from both animals, and the increment of p38 MAPK phosphorylation by the stimulant was diminished in strips from DOCA rats compared to sham-operated rats. These findings suggest that the Ca2+-independent contraction evoked by DPB results from the activation of MAPKs in rat aortic smooth muscle and that the attenuated contractility by DPB in DOCA rat appears to be associated with diminished p38 MAPK activity.

오미자 리그난 화합물의 베타-아밀로이드간 결합 억제 및 해리 효과

유호진(Ho Jin Yu),윤미소(Mi So Yoon),김도윤(Do Yoon Kim),원경종(Kyung-Jong Won),김보경(Bokyung Kim),장상희(Sang-Hee Jang),이환명(Hwan Myung Lee) 대한약학회 2012 약학회지 Vol.56 No.5

The present study tested the effect of Schizandra chinensis lignan compounds, Gomisin A and Schizandrin, on the aggregation and dissociation of beta-amyloid (Aβ)1-42 to explore a possible therapeutic target for Alzheimer's disease. Gomisin A significantly inhibited the Aβ1-42 aggregation in a dose dependent manner, but did not induced the dissociation of aggregated Aβ1-42. On the other hand, Schizandrin significantly suppressed the aggregation and dissociation of Aβ1-42. These results suggest that Gomisin A and Schizandrin, which are known as biologically active ingredients from Schizandra chinensis, may be potentially useful target molecules to develop a drug for the prevention or treatment of Alzheimer's disease.

Tetrahydrobiopterin Inhibits PDGF-stimulated Migration and Proliferation in Rat Aortic Smooth Muscle Cells via the Nitric Oxide Synthase-independent Pathway

Xiaowen Jiang,김보경,Haiyue Lin,이창권,김정완,강현,이필영,원경종,정성호,이환명 대한약리학회 2010 The Korean Journal of Physiology & Pharmacology Vol.14 No.3

Tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide synthase (NOS) activity, is known to play important roles in modulating both NO and superoxide production during vascular diseases such as atherosclerosis. However, the role of BH4 in functions of vascular smooth muscle cells is not fully known. In this study, we tested the effects of BH4 and dihydrobiopterin (BH2), a BH4 precursor, on migration and proliferation in response to platelet-derived growth factor-BB (PDGF-BB) in rat aortic smooth muscle cells (RASMCs). Cell migration and proliferation were measured using a Boyden chamber and a 5-bromo-2'-deoxyuridine incorporation assay, respectively, and these results were confirmed with an ex vivo aortic sprout assay. Cell viability was examined by 2,3-bis [2-methoxy- 4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide assays. BH4 and BH2 decreased PDGF-BB- induced cell migration and proliferation in a dose-dependent manner. The inhibition of cell migration and proliferation by BH4 and BH2 was not affected by pretreatment with NG-nitro-L-arginine methyl ester, a NOS inhibitor. Moreover, the sprout outgrowth formation of aortic rings induced by PDGF-BB was inhibited by BH4 and BH2. Cell viability was not inhibited by BH4 and BH2 treatment. The present results suggest that BH4 and BH2 may inhibit PDGF-stimulated RASMC migration and proliferation via the NOS-independent pathway. Therefore, BH4 and its derivative could be useful for the development of a candidate molecule with an NO-independent anti-atherosclerotic function.

Differential Expression of Proteins Related with Penile Apoptosis in a Rat after Cavernous Nerve Resection

양상국,김보경,Chang Kwan Lee,정홍,김홍섭,류지간,원경종,박승화,이환명 대한남성과학회 2011 The World Journal of Men's Health Vol.29 No.2

Purpose: The mechanism including changes of proteome within cavernosal tissue after cavernous nerve injury were not evaluated. We performed proteomics and functional analysis to identify proteins of penile corpus cavernosum whose expression was or was not altered by cavernous nerve resection (CNR). Materials and Methods: Using 8-week-old male WKY rats, sham and CNR operation under microscope were performed. After 8 weeks, penile tissues of sham and CNR group were harvested. We used 2-DE and MALDI-TOF/TOF (AB 4700) to identify of differently expressed penile proteins. 2-DE gels were stained with silver nitrate and the gels were analyzed with PDQuest. Results: We isolated more than 950 proteins on silver-stained gels of whole protein extracts from normal rat penile corpus cavernous. Of these proteins, 48 prominent proteins were identified using MALDI-TOF/TOF. Protein characterization revealed that the most prominent penile corpus cavernous proteins were those with antioxidant, chaperone, or cytoskeletal structure. Moreover, 11 proteins having levels elevated by CNR were annexin proteins, endoplasmic reticulum protein 29, glutathione s-transferase w-1, and others. In addition, Rho-GDP dissociation inhibitor (RhoGDI), a regulator of Rho proteins, was also increased in CNR rats compared with sham-operated control rats. Conclusions: The apoptotic signals observed in penile tissues was greatly increased in CNR rats than in sham-operated rats. These results suggest that RhoGDI is one of the proteins regulated by CNR in penile smooth muscle strips, and has a crucial role in the early stage of penile apoptosis.

Schizandrin의 신혈관형성억제에 의한 항암효과

윤미소(Mi So Yoon),김도윤(Do Yoon Kim),유호진(Ho Jin Yu),박주훈(Joo-Hoon Park),장상희(Sang Hee Jang),원경종(Kyung-Jong Won),김보경(Bokyung Kim),이환명(Hwan Myung Lee) 한의병리학회 2012 동의생리병리학회지 Vol.26 No.5