• 한국동물학회지
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• 제30권2호
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• pp.177-192
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• 1987

온열처리가 근세포의 분화에 어떤 영향을 미치는 지를 알아보기 위하여 배양한 근세포에 여러가지 온열처리를 한 다음, 단백질 합성, 세포증식, 융합지수, creatine kinase(CK)의 활성 및 cholesterol 함량의 변화를 조사하였다. 배양한지 24시간지나 45$^{\circ}C$에서 1 hr의 온열처리를 하면 근세포의 융합과 CK 활성이 지연되었으며, 55시간지나 같은 온열처리를 하면 세포막내(세포내 양의 95% 이상)의 chloesterol 양이 일시적으로 증가함과 아울러 세포융합이 지연되었다. 그러나 세포증식은 대조군과 뚜렷한 차이가 없었다. 이상과 같은 실험 결과로부터 온열처리가 분화에 미치는 영향은 온열처리를 받게되는 근원세포의 분화정도에 따라 차이가 있으며 온열처리에 따른 chloesterol 양의 일시적인 증가가 근세포 융합에 영향을 미칠 수 있다는 가능성이 제시되었다. 한편, 근세포는 온열처리를 받으면 평소의 단백질 합성 수준이 떨어짐과 더불어 heat shock protein(HSP)합성이 증대 내지는 유도 되었으며 HSP 합성의 유도는 actinomycin D의 처리로 억제되었다. 또한 온열처리로 근세포는 열내성을 얻어 세포융하과 CK 활성은 동일한 온열처리를 4시간 간격으로 두번 주어도 한번 주었을 경우와 차이가 없었으며 두번째 온열처리에 의해서는 새로운 HSP 합성이 유도되지도 않았다.

• Journal of Ginseng Research
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• 제43권1호
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• pp.95-104
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• 2019

Background: Oxidized low-density lipoprotein (ox-LDL) causes vascular endothelial cell inflammatory response and apoptosis and plays an important role in the development and progression of atherosclerosis. Ginsenoside compound K (CK), a metabolite produced by the hydrolysis of ginsenoside Rb1, possesses strong anti-inflammatory effects. However, whether or not CK protects ox-LDL-damaged endothelial cells and the potential mechanisms have not been elucidated. Methods: In our study, cell viability was tested using a 3-(4, 5-dimethylthiazol-2yl-)-2,5-diphenyl tetrazolium bromide (MTT) assay. Expression levels of interleukin-6, monocyte chemoattractant protein-1, tumor necrosis factor-${\alpha}$, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 were determined by enzyme-linked immunosorbent assay and Western blotting. Mitochondrial membrane potential (${\Delta}{\Psi}m$) was detected using JC-1. The cell apoptotic percentage was measured by the Annexin V/ propidium iodide (PI) assay, lactate dehydrogenase, and caspase-3 expression. Apoptosis-related proteins, nuclear factor $(NF)-{\kappa}B$, and mitogen-activated protein kinases (MAPK) signaling pathways protein expression were quantified by Western blotting. Results: Our results demonstrated that CK could ameliorate ox-LDL-induced human umbilical vein endothelial cells (HUVECs) inflammation and apoptosis, $NF-{\kappa}B$ nuclear translocation, and the phosphorylation of p38 and c-Jun N-terminal kinase (JNK). Moreover, anisomycin, an activator of p38 and JNK, significantly abolished the anti-apoptotic effects of CK. Conclusion: These results demonstrate that CK prevents ox-LDL-induced HUVECs inflammation and apoptosis through inhibiting the $NF-{\kappa}B$, p38, and JNK MAPK signaling pathways. Thus, CK is a candidate drug for atherosclerosis treatment.

• Asian Pacific Journal of Cancer Prevention
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• 제13권10호
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• pp.5233-5236
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• 2012

CK2 is a serine threonine kinase that participates in a variety of cellular processes with more than 300 defined substrates. This critical enzyme is known to be upregulated in cancers, but the role of this upregulation in carcinogenesis is not yet fully understood but c-myc, one of the defined CK2 substrates, is a well-known proto-oncogene that is normally essential in developmental process but is also involved in tumor development. We evaluated the optimal enzyme and substrate concentrations for CK2 activity in both neoplastic and non-neoplastic human lung tissues using the c-$myc^{424-434}$ peptide (EQKLISEEDL) as a substrate. The activities measured for the neoplastic tissue were 600-750 U/mg protein while those for the control tissue was in the range of 650-800 U/mg. $K_m$ value for c-myc peptide was determined as $0.33{\mu}M$ in non-neoplastic tissue and $0.18{\mu}M$ in neoplastic tissue. In this study, we did not observe an increased activity in the neoplastic tissue when compared with the non-neoplastic lung tissue, but we recorded two times higher affinity for c-$myc^{424-434}$ in cancer tissue. Considering the metabolic position of c-$myc^{424-434}$, our results suggest that phosphorylation by CK2 may be important in dimerization and thus it might affect the regulation of c-myc in cancer tissues.

• Nutrition Research and Practice
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• 제10권3호
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• pp.259-264
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• 2016

BACKGROUND/OBJECTIVES: Stromal cell-derived growth factor 1 (SDF-1), also known as chemokine ligand 12, and chemokine receptor type 4 are involved in cancer cell migration. Compound K (CK), a metabolite of protopanaxadiol-type ginsenoside by gut microbiota, is reported to have therapeutic potential in cancer therapy. However, the inhibitory effect of CK on SDF-1 pathway-induced migration of glioma has not yet been established. MATERIALS/METHODS: Cytotoxicity of CK in C6 glioma cells was determined using an EZ-Cytox cell viability assay kit. Cell migration was tested using the wound healing and Boyden chamber assay. Phosphorylation levels of protein kinase C $(PKC){\alpha}$ and extracellular signal-regulated kinase (ERK) were measured by western blot assay, and matrix metallopeptidases (MMP) were measured by gelatin-zymography analysis. RESULTS: CK significantly reduced the phosphorylation of $PKC{\alpha}$ and ERK1/2, expression of MMP9 and MMP2, and inhibited the migration of C6 glioma cells under SDF-1-stimulated conditions. CONCLUSIONS: CK is a cell migration inhibitor that inhibits C6 glioma cell migration by regulating its downstream signaling molecules including $PKC{\alpha}$, ERK1/2, and MMPs.

• Molecules and Cells
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• 제42권11호
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• pp.773-782
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• 2019

Cellular senescence is an irreversible form of cell cycle arrest. Senescent cells have a unique gene expression profile that is frequently accompanied by senescence-associated heterochromatic foci (SAHFs). Protein kinase CK2 (CK2) downregulation can induce trimethylation of histone H3 Lys 9 (H3K9me3) and SAHFs formation by activating SUV39h1. Here, we present evidence that the PI3K-AKT-mTOR-reactive oxygen species-p53 pathway is necessary for CK2 downregulation-mediated H3K9me3 and SAHFs formation. CK2 downregulation promotes SUV39h1 stability by inhibiting its proteasomal degradation in a p53-dependent manner. Moreover, the dephosphorylation status of Ser 392 on p53, a possible CK2 target site, enhances the nuclear import and subsequent stabilization of SUV39h1 by inhibiting the interactions between p53, MDM2, and SUV39h1. Furthermore, $p21^{Cip1/WAF1}$ is required for CK2 downregulation-mediated H3K9me3, and dephosphorylation of Ser 392 on p53 is important for efficient transcription of $p21^{Cip1/WAF}$. Taken together, these results suggest that CK2 downregulation induces dephosphorylation of Ser 392 on p53, which subsequently increases the stability of SUV39h1 and the expression of $p21^{Cip1/WAF1}$, leading to H3K9me3 and SAHFs formation.

• The Korean Journal of Physiology and Pharmacology
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• 제24권4호
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• pp.311-317
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• 2020

In the present experimental study, cecal ligation and puncture significantly increased the myocardial injury assessed in terms of excess release of creative kinase-MB (CK-MB), cardiac troponin I (cTnI), interleukin (IL)-6 and decrease of IL-10 in the blood following 12 h of laparotomy procedure as compared to normal control. Also, a significant increase in protein expression levels of high-mobility group box 1 (HMGB1) and decreased phosphorylation of glycogen synthase kinase-3β (GSK-3β) was observed in the myocardial tissue as compared to normal control. A single independent administration of telmisartan (2 and 4 mg/kg) and AR-A014418 (1 and 2 mg/kg) substantially reduced sepsis-induced myocardial injury in terms of decrease levels of CK-MB, cTnI and IL-6, HMGB1, GSK-3β and increase in IL-10 and p-GSK-3β in the blood in sepsis- subjected rats. The effects of telmisartan at dose 4 mg/kg and AR-A014418 at a dose of 2 mg/kg were significantly higher than the telmisartan at a dose of 2 mg/kg and AR-A014418 1 mg/kg respectively. Further, no significant effects on different parameters were observed in the sham control group in comparison to normal. Therefore it is plausible to suggest that sepsis may increase the levels of angiotensin II to trigger GSK-3β-dependent signaling to activate the HMGB1/receptors for advanced glycation end products, which may promote inflammation and myocardial injury in sepsis-subjected rats.

• 운동영양학회지
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• 제23권2호
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• pp.1-6
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• 2019

[Purpose] Strenuous exercise often induces skeletal muscle damage, which results in impaired performance. Sphingolipid metabolism contributes to various cellular processes, including apoptosis, stress response, and inflammation. However, the relationship between exercise-induced muscle damage and ceramide (a key component of sphingolipid metabolism), is rarely studied. The present study aimed to explore the regulatory role of sphingolipid metabolism in exercise-induced muscle damage. [Methods] Mice were subjected to strenuous exercise by treadmill running with gradual increase in intensity. The blood and gastrocnemius muscles (white and red portion) were collected immediately after and 24 h post exercise. For 3 days, imipramine was intraperitoneally injected 1 h prior to treadmill running. [Results] Interleukin 6 (IL-6) and serum creatine kinase (CK) levels were enhanced immediately after and 24 h post exercise (relative to those of resting), respectively. Acidic sphingomyelinase (A-SMase) protein expression in gastrocnemius muscles was significantly augmented by exercise, unlike, serine palmitoyltransferase-1 (SPT-1) and neutral sphingomyelinase (N-SMase) expressions. Furthermore, imipramine (a selective A-SMase inhibitor) treatment reduced the exercise-induced CK and IL-6 elevations, along with a decrease in cleaved caspase-3 (Cas-3) of gastrocnemius muscles. [Conclusion] We found the crucial role of A-SMase in exercise-induced muscle damage.

• Journal of Microbiology and Biotechnology
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• 제17권10호
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• pp.1712-1716
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• 2007

To generate new scaffold candidates as highly selective and potent cyelin-dependent kinase (CDK) inhibitors, structure-based drug screening was performed utilizing 3D pharmacophore conformations of known potent inhibitors. As a result, CR229 (6-bromo-2,3,4,9-tetrahydro-carbolin-1-one) was generated as the hit-compound. A computational docking study using the X-ray crystallographic structure of CDK2 in complex with CR229 was evaluated. This predicted binding mode study of CR229 with CDK2 demonstrated that CR229 interacted effectively with the Leu83 and Glu81 residues in the ATP-binding pocket of CDK2 for the possible hydrogen bond formation. Furthermore, biochemical studies on inhibitory effects of CR229 on various kinases in the human cervical cancer HeLa cells demonstrated that CR229 was a potent inhibitor of CDK2 ($IC_{50}:\;3\;{\mu}M$), CDKI ($IC_{50}:\;4.9\;{\mu}M$), and CDK4 ($IC_{50}:\;3\;{\mu}M$), yet had much less inhibitory effect ($IC_{50}:>20\;{\mu}M$) on other kinases, such as casein kinase 2-${\alpha}1$ (CK2-${\alpha}1$), protein kinase A (PKA), and protein kinase C (PKC). Accordingly, these data demonstrate that CR229 is a potent CDK inhibitor with anticancer efficacy.

• Clinical and Experimental Pediatrics
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• 제53권2호
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• pp.228-234
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• 2010

목 적 : 가와사끼병에서 1차 치료로 고용량 정맥용 면역글로불린(IVIG)의 사용이 가장 효과적인 것으로 알려져 있으나 이 중 약 10-20% 정도는 반응을 보이지 않아 발열이 지속되어 관상동맥의 합병증의 위험이 높아진다고 알려져 있다. 1차 치료에 반응하지 않은 가와사끼병 환자를 조기에 찾기 위한 검사실 지표에 대한 연구가 있으나 일관된 결과를 보이지 않고 있다. 본 연구에서는 IVIG 재 투여를 받은 재 치료군의 임상소견과 검사실 지표분석을 통해 재 치료군의 특징적인 검사 소견을 찾아 보고자 한다. 방 법 : 2003년 3월부터 2008년 2월까지 만 5년간 전남대학교병원 소아청소년과에서 입원하여 치료받았던 가와사끼병 환아 118명을 대상으로 후향적으로 조사하였고 IVIG에 반응을 보인 군(반응군, responder group, n=110)과 IVIG 1회 투여로 반응을 보이지 않아 재 치료 한 군(재 치료군, nonresponder group, n=8)을 비교 평가하였다. 정맥용 면역글로불린(2.0 g/kg) 투여전, 투여 48시간 후, 투여 14일 후의 백혈구 수, 혈색소 수치, 혈소판 수치, ESR, CRP, 총 단백, 알부민, AST, ALT, lactate dehydronase (LDH), BUN, creatinine, creatine kinase (CK), CK-MB 등의 검사실 지표와 나이, 성별, 발열에서 IVIG 투여하기까지 기간 등을 비교 측정하였다. 결 과 : 초기치료에 반응하지 않아 재 치료 한 경우는 118례 중 8례(6.8%) 였다. 이 군에서 IVIG 투여 전 낮은 CK (P =0.03), 높은 총 단백 수치(P <0.01)를 보였고 IVIG 투여 2일 후 높은 백혈구 수치(P =0.04), 중성구 분획(P <0.01)이 통계학적으로 의미 있는 결과로 나타났다. 또한 중성구 분획(P <0.01)과 CK (P =0.01)의 경우 IVIG 투여 전 비해 투여 2일 후 반응군에서 재 치료군보다 큰 폭의 감소를 보였다. 결 론 : 가와사끼병 환아 중 IVIG 투여 전 낮은 CK, 높은 총단백 수치와 IVIG 투여 48시간 후 높은 백혈구 수치, 높은 중성구 분획 보인 환아에서 재 치료 가능성이 높았고, 재 치료군에 비해 반응군에서 CK 등의 감소폭이 큰 점이 특징적이었으며 이의 관련성에 대한 향후 추가적인 연구가 필요할 것으로 생각된다.

• 한국식품영양학회지
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• 제19권2호
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• pp.169-175
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• 2006

단세포 조류 생물인 Chlorella vulgaris(클로렐라)는 다양한 생리 활성을 가진 기능성 소재로 이용되고 있다. 본 연구에서는 강제 수영 부하 실험과 혈액 생화학적 지표에 대한 클로렐라의 효과에 대해 연구하였다. 혈액 생화학적 지표로는 Blood urea nitrogen(BUN), creatine kinase(CK), lactic dehydrogenase(LDH), glucose(Glc), total protein(TP), albumin을 혈액 생화학적 지표로 측정하였다. 매일 0.05, 0.1, 0.15 g/kg 농도의 클로렐라를 각각 실험 군별로 마우스에 구강 투여했다. 클로렐라를 투여한지 3일, 7일째 되는 날 강제 수영 부하 실험을 시행한 결과 0.15 g/kg 클로렐라를 투여한 그룹에서 유의적으로 부동시간을 감소시켰다. 또한 혈청 중 BUN 수치를 낮췄으며, CK, LDH 수치는 감소하는 경향을 나타냈다. 클로렐라 투여 시 혈 중 Glc 수치는 높아졌으나, TP 와 albumin 수치는 변화가 없었다. 이상의 결과들은 클로렐라가 육체적 지구력 향상 효과가 있는 것을 시사하고 있다.