• Title/Summary/Keyword: structural proteins

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Induction of Apoptosis by Pectenotoxin-2 Isolated from Marine Sponges in U937 Human Leukemic Cells (인체 혈구암세포 U937에서 해양해면동물에서 추출된 Pectenotoxin-2에 의한 Apoptosis의 유발에 관한 연구)

  • Shin, Dong Yeok;Kang, Ho Sung;Bae, Song-Ja;Jung, Jee H.;Choi, Yung Hyun
    • Journal of Marine Bioscience and Biotechnology
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    • v.1 no.2
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    • pp.63-70
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    • 2006
  • Natural product compounds are the source of numerous therapeutic agents. The marine environment produces natural products from a variety of structural classes exhibiting activity against numerous disease targets including anticancer agents. Among these, pectenotoxin-2 (PTX-2), which was first identified as a cytotoxic entity in marine sponges, which depolymerizes actin filaments, was found to be highly effective and more potent to activate an intrinsic pathway of apoptosis in p53-deficient tumor cells compared to those with functional p53 both in vitro and in vivo. However, the anti-proliferative mechanism of the compound at non-cytotoxic concentrations has not yet been explored. In the current study, we sought to investigate anti-proliferation and apoptosis of PTX-2 against U937 human leukemic cells and its underlying molecular mechanism. Exposure of U937 cells to PTX-2 resulted in growth inhibition and induction of apoptosis in dose- and time-dependent manner as measured by MTT assay, fluorescent microscopy and flow cytometric analysis. The anti-proliferative effect of PTX-2 was associated with a marked increase in the expression of cyclin-dependent kinase p21 (WAF1/CIP1) mRNA which was tumor suppressor p53-independent. The increase in apoptosis was connected with a time-dependent down-regulation of anti-apoptotic Bcl-XL and inhibitor of apoptosis proteins (IAPs) family such as XIAP and cIAP-2. Though additional studies are needed, these findings suggested that PTX-2-induced inhibition of U937 cells was associated with the induction of apoptotic cell death and the results provided important new insights into the possible molecular mechanisms of the anti-cancer activity of PTX-2.

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Spectroscopic Comparison of Photo-oxidation of Outside and Inside of Hair by UVB Irradiation (자외선B 조사에 의한 모발 외부와 내부의 광산화에 관한 분광학적 비교)

  • Ha, Byung-Jo
    • Applied Chemistry for Engineering
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    • v.31 no.2
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    • pp.220-225
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    • 2020
  • Hair is made of proteins containing various amino acids. Ultraviolet (UV) radiation is believed to be responsible for the most damaging effects of sunlight, and also plays an important role in hair aging. The purpose of this study was to investigate the changes in morphological and chemical structures after ultraviolet B (UVB) irradiation of human hair. The UVB-irradiated hair showed characteristic morphological and structural changes, compared to those of the normal hair. The result from a scanning electron microscope (SEM) equipped with an energy dispersive X-ray diffractometer (EDX) showed that the scale of UV-irradiated hair appeared to be rough and the amount of oxygen element was higher than that of the normal hair. Fluorescence and three dimensional (3D) topographical images were obtained by a confocal laser scanning microscope (CLSM). In 3D images, the green emission intensity of normal hair was much higher than that of fluorescing UVB-irradiated hair. The intensity of green emission reflects the intrinsic fluorescence of hair protein. Also, a fluorescent imaging method using fluorescamine reagent was used to identify the free amino groups resulting from a peptide bond breakage in UVB-irradiated hair. Strong blue fluorescence of UVB-irradiated hair, which indicates a very high level of amino groups, was observed by CLSM. Therefore, the fluorescamine as an extrinsic fluorescence could provide a useful tool to identify the peptide bond breakage in UVB-irradiated hair. Infrared image mapping was also employed to assess the cross-sections of normal and UVB-irradiated specimens to examine the oxidation of disulfide bonds. The degree of peak areas with strong absorbance for the disulfide mono-oxide was spread from the outside to the inside of hair. The spectroscopic techniques used alone, or in combination, launch new possibilities in the field of hair cosmetics.

Structural and Functional Roles of Caspase-8 in Extrinsic Apoptosis (Apoptosis의 외인성 경로에서 caspase-8의 구조적 및 기능적 역할)

  • Ha, Min Seon;Jeong, Mi Suk;Jang, Se Bok
    • Journal of Life Science
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    • v.31 no.10
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    • pp.954-959
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    • 2021
  • Apoptosis is an important mechanism that regulates cellular populations to maintain homeostasis, and the caspases, a family of cysteine proteases, are key mediators of the apoptosis pathway. Caspase-8 is an initiator caspase of the extrinsic apoptotic pathway, which is initiated by extracellular stimuli. Caspase-8 have two conserved domains, N-terminal tandem death effector domains (DED) and C-terminal two catalytic domain, which are important for this extrinsic apoptosis pathway. In extrinsic apoptosis pathway, death receptors which members of TNF superfamily are activated by binding of death receptor specific ligands from cell outside. After the activated death receptors recruit adaptor protein Fas-associated death domain protein (FADD), death domains (DD) of death receptor and FADD bind to each other and FADD combined with death receptor recruits procaspase-8, a precursor form of caspase-8. The DED of FADD and procaspase-8 bind to one another and FADD-bound procaspase-8 is activated by cleavage of the prodomain. This death receptor-FADD-caspase-8 complex called death inducing signaling complex (DISC). Cellular FLICE-inhibitory proteins (c-FLIPs) regulate caspase-8 activation by acting both anti- and pro-apoptotically, and caspase-8 activation initiates the activation of executioner caspases such as caspase-3. Finally activated executioner caspases complete the apoptosis by acting critically DNA degradation, nuclear condensation, plasma membrane blebbing, and the proteolysis of certain caspase substrates.

Role of Peptides in Antiviral (COVID-19) Therapy

  • Chelliah, Ramachandran;Daliri, Eric Banan-Mwine;Elahi, Fazle;Yeon, Su-Jung;Tyagi, Akanksha;Park, Chae Rin;Kim, Eun Ji;Jo, kyoung Hee;Oh, Deog-Hwan
    • Journal of Food Hygiene and Safety
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    • v.36 no.5
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    • pp.363-375
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    • 2021
  • Trends in the developing era to discover and design peptide-based treatments throughout an epidemic infection scenario such as COVID-19 could progress into a more efficient and low-cost therapeutic environment. However, the weakening of proteolysis is one downside of natural peptide drugs. But, peptidomimetics may help resolve this issue. In this review, peptide and peptide-based drug discovery were summarized to target one key entry mechanism of severe coronavirus pulmonary emboli syndrome (SARS-CoV-2), which encompasses the association of the host angiotensin-converting enzyme-2 (ACE2) receptor and viral spike (S) protein. Furthermore, the benefits of proteins, peptides and other possible actions that have been studied for COVID-19 through new peptide-based treatments are discussed in the review. Lastly, an overview of the peptide-based drug therapy environment is comprised of an evolutionary viewpoint, structural properties, operational thresholds, and an explanation of the therapeutic area.

Expression of H-ras, RLIP76 mRNA and Protein, and Angiogenic Receptors in Corpus Luteum Tissues during Estrous Cycles (난소 내 황체조직에서 발정주기별 H-Ras, RLIP76, Angiogenic Receptors mRNA와 Protein의 발현)

  • Kim, Minseong;Lee, Sang-Hee;Lee, Seunghyung
    • Korean Journal of Clinical Laboratory Science
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    • v.50 no.4
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    • pp.457-461
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    • 2018
  • Corpus luteum (CL) is a transient endocrinal tissue that undergoes repeated formation and regression during the estrous cycle. In this study, we hypothesized that the functional and structural mechanism of angiogenesis is similar between CL and tumor formation. First, we measured mRNA and protein expression of angiogenic receptors (vascular endothelial growth factor receptor-2, VEGFR2; Tie 2) in the early, middle, and late phase CL tissues during the estrous cycle. Ral-interacting protein of 76 kDa (RLIP76) and H-ras mRNA and protein were also expressed in the CL tissues. VEGFR2 and Tie 2 mRNA and protein were expressed in the early and middle phase CLs and decreased in the late phase. H-ras mRNA and protein were expressed in the early and middle phase CLs, but not in the late phase. RLIP76 mRNA was expressed in all phase CLs, and the protein expression was highest in early phase CLs. We suggest that RLIP76 and H-ras, an oncogenic gene, regulate the function of the CL during the estrous cycle, and the proteins will play an important role in the angiogenic mechanism of the CL.

Natural and synthetic pathogen associated molecular patterns modulate galectin expression in cow blood

  • Asiamah, Emmanuel Kwaku;Ekwemalor, Kingsley;Adjei-Fremah, Sarah;Osei, Bertha;Newman, Robert;Worku, Mulumebet
    • Journal of Animal Science and Technology
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    • v.61 no.5
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    • pp.245-253
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    • 2019
  • Pathogen-associated Molecular Patterns (PAMPs) are highly conserved structural motifs that are recognized by Pathogen Recognition receptors (PRRs) to initiate immune responses. Infection by these pathogens and the immune response to PAMPS such as lipopolysaccharide (LPS), Peptidoglycan (PGN), bacterial oligodeoxynucleotides [CpG oligodeoxynucleotides 2006 (CpG ODN2006) and CpG oligodeoxynucleotides 2216 (CpG ODN2216)], and viral RNA Polyinosinic-Polycytidylic Acid (Poly I:C), are associated with infectious and metabolic diseases in animals impacting health and production. It is established that PAMPs mediate the production of cytokines by binding to PRRs such as Toll-like receptors (TLR) on immune cells. Galectins (Gal) are carbohydrate-binding proteins that when expressed play essential roles in the resolution of infectious and metabolic diseases. Thus it is important to determine if the expression of galectin gene (LGALS) and Gal secretion in blood are affected by exposure to LPS and PGN, PolyI:C and bacterial CpG ODNs. LPS increased transcription of LGALS4 and 12 (2.5 and 2.02 folds respectively) and decreased secretion of Gal 4 (p < 0.05). PGN increased transcription of LGALS-1, -2, -3, -4, -7, and -12 (3.0, 2.3, 2.0, 4.1, 3.3, and 2.4 folds respectively) and secretion of Gal-8 and Gal-9 (p < 0.05). Poly I:C tended to increase the transcription of LGALS1, LGALS4, and LGALS8 (1.78, 1.88, and 1.73 folds respectively). Secretion of Gal-1, -3, -8 and nine were significantly increased in treated samples compared to control (p < 0.05). CpG ODN2006 did not cause any significant fold changes in LGALS transcription (FC < 2) but increased secretion of Gal-1, and-3 (p < 0.05) in plasma compared to control. Gal-4 was however reduced in plasma (p < 0.05). CpG ODN2216 increased transcription of LGALS1 and LGALS3 (3.8 and 1.6 folds respectively), but reduced LGALS2, LGALS4, LGALS7, and LGALS12 (-1.9, -2.0, -2.0 and; -2.7 folds respectively). Secretion of Gal-2 and -3 in plasma was increased compared to control (p < 0.05). Gal-4 secretion was reduced in plasma (p < 0.05). The results demonstrate that PAMPs differentially modulate galectin transcription and translation of galectins in cow blood.

Coronaviruses: SARS, MERS and COVID-19 (코로나바이러스: 사스, 메르스 그리고 코비드-19)

  • Kim, Eun-Joong;Lee, Dongsup
    • Korean Journal of Clinical Laboratory Science
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    • v.52 no.4
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    • pp.297-309
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    • 2020
  • Coronaviruses were originally discovered as enzootic infections that limited to their natural animal hosts, but some strains have since crossed the animal-human species barrier and progressed to establish zoonotic diseases. Accordingly, cross-species barrier jumps resulted in the appearance of SARS-CoV, MERS-CoV, and SARS-CoV-2 that manifest as virulent human viruses. Coronaviruses contain four main structural proteins: spike, membrane, envelope, and nucleocapsid protein. The replication cycle is as follows: cell entry, genome translation, replication, assembly, and release. They were not considered highly pathogenic to humans until the outbreaks of SARS-CoV in 2002 in Guangdong province, China. The consequent outbreak of SARS in 2002 led to an epidemic with 8,422 cases, and a reported worldwide mortality rate of 11%. MERS-CoVs is highly related to camel CoVs. In 2019, a cluster of patients infected with 2019-nCoV was identified in an outbreak in Wuhan, China, and soon spread worldwide. 2019-nCoV is transmitted through the respiratory tract and then induced pneumonia. Molecular diagnosis based on upper respiratory region swabs is used for confirmation of this virus. This review examines the structure and genomic makeup of the viruses as well as the life cycle, diagnosis, and potential therapy.

The Effect of Low Molecule Collagen Peptide on Skin Anti-glycation and Collagen Synthesis as a Skin Aging Therapy (피부 노화 치료로서 저분자콜라겐펩타이드의 피부 항당화와 콜라겐 합성 효과)

  • Kim, Hong Seok;Hong, Won Kyu;Lee, Mun Hoe;Kim, Hyeong Min;Chung, Hee Chul;Lee, Jin Hee
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.47 no.2
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    • pp.147-153
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    • 2021
  • Collagen hydrolysate (CH) is known to prevent skin aging by stimulating skin dermal fibroblasts to promote synthesis of extracellular matrix such as collagen and elastin. Recently, among the various factors that cause skin aging, advanced glycation end products (AGEs) have received particular attention. However, the effect of CH on AGE accumulation has not been studied. Since CH could affect AGE accumulation by promoting production of skin structural proteins, clinical trial was performed using low molecule collagen peptide (LMCP), which were CH containing 25% tripeptide and 4% Gly-Pro-Hyp. Skin autofluorescence (SAF) values were measured using an AGE reader to evaluate accumulation of AGE in skin. As a result of applying 0.5% and 1.0% LMCP solutions to the subject's forearm for 8 weeks, the SAF value at the test site significantly decreased compared to the control site. Additionally, in vitro test was performed using CCD-986sk to evaluate the promotion of collagen synthesis in skin fibroblasts by LMCP. As a result, 800 ㎍/mL of LMCP significantly increased synthesis of human pro-collagen Iα1 (COL1A1) in CCD-986sk. Through this study, we have confirmed that tropical LMCP applications can promote collagen synthesis to help anti-glycation effects, suggesting that LMCP has potential as an anti-aging cosmetic material.

3D Printing-Based Ultrafast Mixing and Injecting Systems for Time-Resolved Serial Femtosecond Crystallography (시간 분해 직렬 펨토초 결정학을 위한 3차원 프린팅 기반의 초고속 믹싱 및 인젝팅 시스템)

  • Ji, Inseo;Kang, Jeon-Woong;Kim, Taeyung;Kang, Min Seo;Kwon, Sun Beom;Hong, Jiwoo
    • Korean Chemical Engineering Research
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    • v.60 no.2
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    • pp.300-307
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    • 2022
  • Time-resolved serial femtosecond crystallography (TR-SFX) is a powerful technique for determining temporal variations in the structural properties of biomacromolecules on ultra-short time scales without causing structure damage by employing femtosecond X-ray laser pulses generated by an X-ray free electron laser (XFEL). The mixing rate of reactants and biomolecule samples, as well as the hit rate between crystal samples and x-ray pulses, are critical factors determining TR-SFX performance, such as accurate image acquisition and efficient sample consumption. We here develop two distinct sample delivery systems that enable ultra-fast mixing and on-demand droplet injecting via pneumatic application with a square pulse signal. The first strategy relies on inertial mixing, which is caused by the high-speed collision and subsequent coalescence of droplets ejected through a double nozzle, while the second relies on on-demand pneumatic jetting embedded with a 3D-printed micromixer. First, the colliding behaviors of the droplets ejected through the double nozzle, as well as the inertial mixing within the coalesced droplets, are investigated experimentally and numerically. The mixing performance of the pneumatic jetting system with an integrated micromixer is then evaluated by using similar approaches. The sample delivery system devised in this work is very valuable for three-dimensional biomolecular structure analysis, which is critical for elucidating the mechanisms by which certain proteins cause disease, as well as searching for antibody drugs and new drug candidates.

Current Status of Korean Ginseng Research (한국인삼론(韓國人蔘論))

  • Han, Byung-Hoon
    • Korean Journal of Pharmacognosy
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    • v.3 no.3
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    • pp.151-160
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    • 1972
  • Recent achievements of scientific research on the pharmacologic activities and the chemical problems of dammalene glycosides, which are considered to be effective principles of Korean ginseng, are reviewed and analyzed in view of structure-activity relationship. 1) S. Shibata and his co-workers detected 12 glycoside spots of dammalene series on the two dimensional T.L.C. of total glycoside fraction from Japanese ginseng, and designated them Ginsenoside Rx(x=a, b, c, g, h, etc.) in the order of increasing Rf-value. The aglycones of those glycosides were characterized to be protopanaxadiol for the Ginsenoside $Rx(x=a,\;b_{1},\;b_{2},\;c,\;d,\;e,\;f)$ and protopanaxatriol for the Ginsenoside $Rx(x=g_{1},\;g_{2},\;g_{3},\;h_{1}\;'h_{2})$. Using Korean ginseng as the material for our study, the author and his coworkers isolated a new dammalene glycoside(Panax Saponin C), which comes under the category of protopanaxadiol glycosides based on the classification of S. Shibata et al., and characterized this saponin to be the glycoside of protopanaxatriol series. Furthermore, Panax Saponin C dissociated into $two\;components(C_{1}\;and\;C_{2}-acetate)$ by acetylation, both of which returned to original Panax Saponin C by deacetylation. Based on this result, more than 13 glycoside components of dammalene series will be expected in the Korean ginseng. 2) The structures of protopanaxadiol and protopanaxatriol, the genuine aglycones of dammalene glycosides, are fully established to be structural analogues by S. Shibata and his co-workers, therefore antagonistic and/or analogical activities will be expected for the pharmacologic activities of these glycoside series of structural analogues. K. Takaki and his co-workers found central nervous system (CNS) stimmulant activity from the glycosides of protopanaxatriol series and CNS-depressant activity from the glycosides of protopanaxadiol series. On the other hand, the author and his co-workers found stimmulating activity on the protein synthesis from both the series of dammalene glycosides with delayed and long-lasting characteristics. This delayed and long-lasting characteristics were also observed in the anti-inflammatory activity of glycosides of protopanaxatriol series on their time course tendency. For the convenience's sake of argument, pluralistic pharmacologic activities of dammalene glycosides, which were observed by many workers at various pharmacologic site, may be classified into two main categories; one is pan-cellular activity and the other is organ specific activity to the certain tissue which is a mass of cells differentiated to a certain direction for their special functions in the body. Based on the data of K. Takaki and those of the authors, following assumption will be probable; Pharmacologic activities of both series of glycosides of protopanaxadiol and protopanaxatriol aglycones may be antagonistic on their tissue-specific activities and analogic on their pan-cellular activities. Therefore, the mixture of these two series of glycosides in an appropriate ratio, as the case of total extract of Korean ginseng, will be probably beneficial to the host by increasing the synthesis of some functional proteins, due to the additive action of pan-cellular activity, and with the disappearance of any significant behavioral symptoms due to the antagonism of tissue specific activity. This fact will probably be the main reason why classical trials of pharmacologists failed in re-discovering the efficacy of Korean ginseng with their behavioral test. 3) The author and his co-workers achieved the synthesis of $C^{14}-labelled\;Panax\;Saponin\;A\;on\;C_{25}-C_{27}\;position\;of\;aglycone$ in the interest of tracer studies in vivo. The method will be applicable to other dammalene glycosides regardless of their chemical structure. 4) The author and his co-workers converted chemically betulafolienetriol, a triterpene component of Betula platyphylla, to the protopanaxadiol, one of genuine aglycone of dammalene glycosides.

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