• Molecules and Cells
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• 제26권5호
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• pp.415-426
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• 2008

The interactions between the host and microbial pathogen largely dictate the onset, progression, and outcome of infectious diseases. Pathogens subvert host components to promote their pathogenesis and, among these, cell surface heparan sulfate proteoglycans are exploited by many pathogens for their initial attachment and subsequent cellular entry. The ability to interact with heparan sulfate proteoglycans is widespread among viruses, bacteria, and parasites. Certain pathogens also use heparan sulfate proteoglycans to evade host defense mechanisms. These findings suggest that heparan sulfate proteoglycans are critical in microbial pathogenesis, and that heparan sulfate proteoglycan-pathogen interactions are potential targets for novel prophylactic and therapeutic approaches.

• Biodesign
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• 제5권3호
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• pp.122-125
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• 2017

Receptor for advanced glycation end products (RAGE) is one of the single transmembrane domain containing receptors and causes various inflammatory diseases including diabetes and atherosclerosis. RAGE extracellular domain has three consecutive IgG-like domains (V-C₁-C₂ domain) which interact with various soluble ligands including heparan sulfate or HMGB1. Studies have shown that each ligand induces different oligomeric forms of RAGE which results in a ligand-specific signal transduction. The structure of mouse RAGE bound to heparan sulfate has been previously determined but the electron density map of heparan sulfate was too ambiguous that the exact position of heparin sulfate could not be defined. Furthermore, the complex structure of human RAGE and heparin sulfate still remains elusive. Therefore, to determine the structure, human RAGE was overexpressed using bacterial expression system and crystallized using the sitting drop method in the condition of 0.1 M sodium acetate trihydrate pH 4.6, 8 % (w/v) polyethylene glycol 4,000 at 290 K. The crystal diffracted to 3.6 Å resolution and the space group is C121 with unit cell parameters a= 206.04 Å, b= 68.64 Å, c= 98.73 Å, α= 90.00°, β= 90.62°, γ= 90.00°.

• Molecules and Cells
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• 제27권5호
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• pp.503-513
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• 2009

Proteoglycans located in basement membranes, the nanostructures underling epithelial and endothelial layers, are unique in several respects. They are usually large, elongated molecules with a collage of domains that share structural and functional homology with numerous extracellular matrix proteins, growth factors and surface receptors. They mainly carry heparan sulfate side chains and these contribute not only to storing and preserving the biological activity of various heparan sulfate-binding cytokines and growth factors, but also in presenting them in a more "active configuration" to their cognate receptors. Abnormal expression or deregulated function of these proteoglycans affect cancer and angiogenesis, and are critical for the evolution of the tumor microenvironment. This review will focus on the functional roles of the major heparan sulfate proteoglycans from basement membrane zones: perlecan, agrin and collagen XVIII, and on their roles in modulating cancer growth and angiogenesis.

• Journal of Periodontal and Implant Science
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• 제30권3호
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• pp.599-610
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• 2000

Gingival fibroblasts are embedded in an extracellular matrix. The matrixs have influence on the development, polarity, and behavior of nearby cells. The major component of periodontal extracellular matrix is a glycosaminoglycan. The glycosaminoglycan are large carbohydrates that are composed of repeating disaccharide units and exist in three main form: dermatan sulfate, chondrotitin sulfate, heparan sulfate. The purpose of present study is to examine the biologic effects of glycosaminoglycan on human gingival fibroblast. Human gingival fibroblasts were supplemented with each glycosaminoglycan, and cellular attachment and proliferation was determined by MTT assay. Dermatan sulfate and chondroitin sulfate did not stimulate the attachment and proliferation of human gingival fibroblasts, but heparan sulfate increased the proliferation and attachment in a time- and dose dependent manner. These results indicated that heparan sulfate seems to have a high potential for gingival regeneration and root surface attachment.

• 대한유전성대사질환학회지
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• 제15권1호
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• pp.44-48
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• 2015

뮤코다당증 제3A형(Mucopolysaccharidosis IIIA, Sanfillippo syndrome type A)은 heparan sulfate 대사에 관여하는 heparan N-sulfatase의 결핍으로 유발되는 리소좀 축적 질환이다. 본 연구는 대두증과 발달 지연을 보이는 5세 환아를 대상으로 하였다. 환아 소변의 glycosaminoglycan은 26 g/moL creatinine으로 증가되어 있었고(참고치: <7 g/moL creatinine), 소변의 전기영동 검사에서는 heparan sulfate 분획이 뚜렷하게 관찰되었다. 피부 섬유아세포에서 측정한 heparan N-sulfatase 활성도는 0.2 pmol/min/mg protein으로 매우 감소되어 있었다(참고치: 9-64 pmol/min/mg protein). 중합효소연쇄반응-염기서열분석법에 의한 SGSH 유전자 검사에서는 c.1040C>T (p.S347F) 및 c.703G>A (p.D235N) 돌연변이가 각각 이형접합체 양상으로 나타났다. 이에 생화학적 검사 및 분자유전학적 검사를 통해 뮤코다당증 제3A형으로 확진된 첫 번째 한국인 사례를 보고하는 바이다.

• Molecules and Cells
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• 제24권2호
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• pp.153-166
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• 2007

The syndecan family of heparan sulfate proteoglycans is expressed on the surface of all adherent cells. Syndecans interact with a wide variety of molecules, including growth factors, cytokines, proteinases, adhesion receptors and extracellular matrix components, through their heparan sulfate chains. Recent studies indicate that these interactions not only regulate key events in development and homeostasis, but also key mechanisms of the host inflammatory response. This review will focus on the molecular and cellular aspects of how syndecans modulate tissue injury and inflammation, and how syndecans affect the outcome of inflammatory diseases in vivo.

• BMB Reports
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• 제37권6호
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• pp.684-690
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• 2004

Heparin lyase I was purified to homogeneity from Bacteroides stercoris HJ-15 isolated from human intestine, by a combination of DEAE-Sepharose, gel-filtration, hydroxyapatite, and CM-Sephadex C-50 column chromatography. This enzyme preferred heparin to heparan sulfate, but was inactive at cleaving acharan sulfate. The apparent molecular mass of heparin lyase I was estimated as 48,000 daltons by SDS-PAGE and its isoelectric point was determined as 9.0 by IEF. The purified enzyme required 500 mM NaCl in the reaction mixture for maximal activity and the optimal activity was obtained at pH 7.0 and $50^{\circ}C$. It was rather stable within the range of 25 to $50^{\circ}C$ but lost activity rapidly above $50^{\circ}C$. The enzyme was activated by $Co^{2+}$ or EDTA and stabilized by dithiothreitol. The kinetic constants, $K_m$ and $V_{max}$ for heparin were $1.3{\times}10^{-5}\;M$ and $8.8\;{\mu}mol/min{\cdot}mg$. The purified heparin lyase I was an eliminase that acted best on porcine intestinal heparin, and to a lesser extent on porcine intestinal mucosa heparan sulfate. It was inactive in the cleavage of N-desulfated heparin and acharan sulfate. In conclusion, heparin lyase I from Bacteroides stercoris was specific to heparin rather than heparan sulfate and its biochemical properties showed a substrate specificity similar to that of Flavobacterial heparin lyase I.

• 대한미생물학회지
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• 제34권5호
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• pp.435-443
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• 1999

Orientia tsutsugamushi is obligate intracellular bacterium that grows within the cytoplasm of the eukaryotic host cells. Therefore capability of the attachment, entry into the host cell and intracellular survival should be critical process for oriential infection. In this study we investigated the cellular invasion mechanism of Orientia tsutsugamushi and the role of transmembrane heparan sulfate proteoglycan, which binds diverse components at the cellular microenvironment and is implicated as host cell receptors for a variety of microbial pathogens. First of all Orientia tsutsugamushi can invade a wide range of nonprofessional phagocytic cells including fibroblast, epithelial cells and endothelial cells of various host species, including Band T lymphocytes. Thus, it was postulated that the attachment of O. tsutsugamushi requires the recognition of ubiquitous surface structures of many kinds of host cells. Treatments with heparan sulfate and heparin inhibited the infection of Orientia tsutsugamushi in dose-dependent manner for L cell, mouse fibroblast, whereas other glycosaminoglycans such as chondroitin sulfate had no effect. Collectively, these findings provide strong evidence that initial interaction with heparan sulfate proteoglycan is required for the oriential invasion into host cells.

• Pediatric Infection and Vaccine
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• 제29권2호
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• pp.70-76
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• 2022

코로나바이러스감염증-19 (COVID-19)의 임상 양상은 무증상부터 급성 호흡곤란 증후군에 이르기까지 다양하다. 점액 다당류증(mucopolysaccharidosis) 2형은글라이코스아미노글라이칸(glycosaminoglycan)의 일종인 헤파란 황산염(heparan sulfate)과 더마탄 황산염(dermatan sulfate)의 분해를 촉매하는 효소 결핍에 의해 상기 물질이 리소좀(lysosome)에 축적되는 질환으로 전신 침범, 특히 호흡기침범을 특징으로 한다. 따라서 박테리아나 바이러스에 의한 호흡기 감염은 예후에 치명적일 수 있다. 현재 점액 다당류증 환자에서 제 2형 중증급성호흡기증후군 코로나 바이러스(SARS-CoV-2) 감염 후의 임상 양상에 대한 보고는 매우 드물고, 이에 점액 다당류증 2형으로 효소대체요법을 받고 있던 환자에서 상기 바이러스 감염 후의 임상 양상에 대해 보고하고 관련 문헌에 대해 고찰하고자 한다. 16세 남아로 가족간 전파로 코로나바이러스감염증이 발생하였다. 콧물, 기침, 가래 등 호흡기 증상이 관찰되었다. 발열이나 산소요구도 증가는 없었으며 심박수, 호흡수, 산소 포화도는 정상 범위였고 혈액검사결과에서 백혈구 감소증이 관찰되었다. 흉부 방사선 사진에서 폐렴 소견은 보이지 않았다. 보존적 치료와 격리만으로 증상이 호전되었다. 경미한 임상 양상의 원인으로 전구 물질의 축적으로 인해 바이러스에게 불리한 숙주의 세포 환경, 바이러스와의 상호작용에 관여하는 단백질을 암호화하는 유전자 발현의 특정방향으로의 변화가 제시되고 있다. 또한 점액 다당류증 환자에서 증가된 혈청 헤파란 황산염이 SARS-CoV-2 스파이크 단백질과 숙주 세포의 상호작용에 필수적인 세포 표면의 헤파란 황산염과 경쟁하여 SARS-CoV-2의 세포 내 침투로부터 보호한다는 가설도 있다. 향후 더 많은 사례를 통해 점액 다당류증 등의 리소좀 축적질환에서 코로나바이러스감염증의 발현 양상에 대한 연구가 필요하다.

• Molecules and Cells
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• 제41권7호
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• pp.622-630
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• 2018

Leukocyte common antigen-related protein tyrosine phosphatases (LAR-RPTPs) are cellular receptors of heparan sulfate (HS) and chondroitin sulfate (CS) proteoglycans that regulate neurite outgrowth and neuronal regeneration. LAR-RPTPs have also received particular attention as the major presynaptic hubs for synapse organization through selective binding to numerous postsynaptic adhesion partners. Recent structural studies on LAR-RPTP-mediated trans-synaptic adhesion complexes have provided significant insight into the molecular basis of their specific interactions, the key codes for their selective binding, as well as the higher-order clustering of LAR-RPTPs necessary for synaptogenic activity. In this review, we summarize the structures of LAR-RPTPs in complex with various postsynaptic adhesion partners and discuss the molecular mechanisms underlying LAR-RPTP-mediated synaptogenesis.