• Title/Summary/Keyword: CK7

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Compound K, a ginsenoside metabolite, plays an antiinflammatory role in macrophages by targeting the AKT1-mediated signaling pathway

  • Lee, Jeong-Oog;Choi, Eunju;Shin, Kon Kuk;Hong, Yo Han;Kim, Han Gyung;Jeong, Deok;Hossain, Mohammad Amjad;Kim, Hyun Soo;Yi, Young-Su;Kim, Donghyun;Kim, Eunji;Cho, Jae Youl
    • Journal of Ginseng Research
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    • v.43 no.1
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    • pp.154-160
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    • 2019
  • Background: Compound K (CK) is an active metabolite of ginseng saponin, ginsenoside Rb1, that has been shown to have ameliorative properties in various diseases. However, its role in inflammation and the underlying mechanisms are poorly understood. In this report, the antiinflammatory role of CK was investigated in macrophage-like cells. Methods: The CK-mediated antiinflammatory mechanism was explored in RAW264.7 and HEK293 cells that were activated by lipopolysaccharide (LPS) or exhibited overexpression of known activation proteins. The mRNA levels of inflammatory genes and the activation levels of target proteins were identified by quantitative and semiquantitative reverse transcription polymerase chain reaction and Western blot analysis. Results: CK significantly inhibited the mRNA expression of inducible nitric oxide synthase and tumor necrosis factor-${\alpha}$ and morphological changes in LPS-activated RAW264.7 cells under noncytotoxic concentrations. CK downregulated the phosphorylation of AKT1, but not AKT2, in LPS-activated RAW264.7 cells. Similarly, CK reduced the AKT1 overexpression-induced expression of aldehyde oxidase 1, interleukin-$1{\beta}$, interferon-${\beta}$, and tumor necrosis factor-${\alpha}$ in a dose-dependent manner. Conclusion: Our results suggest that CK plays an antiinflammatory role during macrophage-mediated inflammatory actions by specifically targeting the AKT1-mediated signaling pathway.

A Clinical Analysis of 24 cases of Cardiac Contusion and Cardiac Concussion (둔상에 의한 심타박상과 심좌상의 임상적 고찰)

  • 이계선;정진악;금동윤;안정태;이재원;신제균
    • Journal of Chest Surgery
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    • v.32 no.3
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    • pp.270-275
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    • 1999
  • Background: In the patients with thoracic injury, we suspect simultaneous cardiac contusion or concussion. We analyzed the patients with possible cardiac injury by electrocardiography, serum creatine kinase (CK), creatine kinase isoenzyme fraction (CK-MB) screening, followed by two dimentional echocardiogram (2-DE) to access the severity of injury. Material and Method: From January 1997 to April 1998, 15-month retrospective study of suspicious myocardial injury was undertaken in including 24 patients admitted for suspected cardiac injury. All patients with history or signs of blunt chest injury were checked serially and the serial CK, CK-MB fraction, electrocardiography (EKG) analysis screening were followed by 2-DE. Result: The age range was between 20-40 years and were predominant male patients in(M:F=3:1). Most common causes of injury were traffic accidents, 15 patients(62.5%). Associated injuries involved multiple rib fractures, sternal fracture and such. EKG findings on the cardiac concussion were within normal limits, EKG findings on the cardiac contusion were nonspecific ST and T wave abnormality. In cardiac contusion patients, CK-MB fraction did not increase significantly on admission but on 2nd, 3rd, 4th hospital days, it increased significantly (p=0.0080, 0.0130, 0.0130). The average admission days were 9.22 in concussion and 26.18 in contusion patients(p=0.0075). Most common complication was the adult respiratory distress syndrome(7 cases), 5 out of the patients with ARDS were mechanically ventilated. There were no deaths. Conclusion: We believe the serial checks of CK-MB, EKG and subsquent two-dementional echocardiographic sector scanning are presently the most sensitive indicators available for structural and functional cardiac injury.

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Enhanced antidiabetic efficacy and safety of compound K/β-cyclodextrin inclusion complex in zebrafish

  • Nam, Youn Hee;Le, Hoa Thi;Rodriguez, Isabel;Kim, Eun Young;Kim, Keonwoo;Jeong, Seo Yule;Woo, Sang Ho;Lee, Yeong Ro;Castaneda, Rodrigo;Hong, Jineui;Ji, Min Gun;Kim, Ung-Jin;Hong, Bin Na;Kim, Tae Woo;Kang, Tong Ho
    • Journal of Ginseng Research
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    • v.41 no.1
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    • pp.103-112
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    • 2017
  • Background: 20(S)-Protopanaxadiol 20-O-D-glucopyranoside, also called compound K (CK), exerts antidiabetic effects that are mediated by insulin secretion through adenosine triphosphate (ATP)-sensitive potassium ($K_{ATP}$) channels in pancreatic ${\beta}$-cells. However, the antidiabetic effects of CK may be limited because of its low bioavailability. Methods: In this study, we aimed to enhance the antidiabetic activity and lower the toxicity of CK by including it with ${\beta}$-cyclodextrin (CD) (CD-CK), and to determine whether the CD-CK compound enhanced pancreatic islet recovery, compared to CK alone, in an alloxan-induced diabetic zebrafish model. Furthermore, we confirmed the toxicity of CD-CK relative to CK alone by morphological changes, mitochondrial damage, and TdT-UTP nick end labeling (TUNEL) assays, and determined the ratio between the toxic and therapeutic dose for both compounds to verify the relative safety of CK and CD-CK. Results: The CD-CK conjugate ($EC_{50}=2.158{\mu}M$) enhanced the recovery of pancreatic islets, compared to CK alone ($EC_{50}=7.221{\mu}M$), as assessed in alloxan-induced diabetic zebrafish larvae. In addition, CD-CK ($LC_{50} =20.68{\mu}M$) was less toxic than CK alone ($LC_{50}=14.24{\mu}M$). The therapeutic index of CK and CD-CK was 1.98 and 9.58, respectively. Conclusion: The CD-CK inclusion complex enhanced the recovery of damaged pancreatic islets in diabetic zebrafish. The CD-CK inclusion complex has potential as an effective antidiabetic efficacy with lower toxicity.

CK2 phosphorylates AP-2α and increases its transcriptional activity

  • Ren, Kaiqun;Xiang, Shuanglin;He, Fangli;Zhang, Wenfeng;Ding, Xiaofeng;Wu, Yanyang;Yang, Liping;Zhou, Jianlin;Gao, Xiang;Zhang, Jian
    • BMB Reports
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    • v.44 no.7
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    • pp.490-495
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    • 2011
  • Transcription factor AP-$2{\alpha}$ involves in the process of mammalian embryonic development and tumorigenesis. Many studies have shown that AP-$2{\alpha}$ functions in association with other interacting proteins. In a two-hybrid screening, the regulatory subunit ${\beta}$ of protein casein kinase 2 ($CK2{\beta}$) was identified as an interacting protein of AP-$2{\alpha}$; we confirmed this interaction using in-vitro GST pull-down and in-vivo co-immunoprecipitation assays; in an endogenous co-immunoprecipitation experiment, we further found the catalytic subunit ${\alpha}$ of protein casein kinase 2 ($CK2{\alpha}$) also exists in the complex. Phosphorylation analysis revealed that AP-$2{\alpha}$ was phosphorylated by CK2 kinase majorly at the site of Ser429, and such phosphorylation could be blocked by CK2 specific inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB) in a dose-dependent manner. Luciferase assays demonstrated that both $CK2{\alpha}$ and $CK2{\beta}$ enhanced the transcription activity of AP-$2{\alpha}$; moreover, $CK2{\beta}$ increased the stability of AP-$2{\alpha}$. Our data suggest a novel cellular function of CK-2 as a transcriptional co-activator of AP-$2{\alpha}$.

Cardiac Damage Biomarkers Following a Triathlon in Elite and Non-elite Triathletes

  • Park, Chan-Ho;Kim, Kwi-Baek;Han, Jin;Ji, Jin-Goo;Kwak, Yi-Sub
    • The Korean Journal of Physiology and Pharmacology
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    • v.18 no.5
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    • pp.419-423
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    • 2014
  • The purpose of the present study was to investigate cardiac damage biomarkers after a triathlon race in elite and non-elite athlete groups. Fifteen healthy men participated in the study. Based on performance, they were divided into elite athlete group (EG: n=7) and non-elite athlete group (NEG: n=8). Participants' blood samples were obtained during four periods: before, immediately, 2 hours and 7 days after finishing the race. creatine kinase (CK), creatine kinase-myoglobin (CK-MB), myoglobin, and lactate dehydrogenase (LDH) were significantly increased in both groups immediately after, and 2 hours after finishing the race (p<.05). CK, CK-MB, and myoglobin were completely recovered after 7 days (p<.05). Hematocrit (Hct) was significantly decreased in both groups (p<.05) 7 days after the race. LDH was significantly decreased in the EG (p<.05) only 7 days after the race. Homoglobin (Hb) was significantly decreased in the NEG (p<.05) only 2 hours after the race. Although cardiac troponin T (cTnT) was significantly increased in the EG but not in the NEG 2hours after the race (p<.05), there was no group-by-time interaction. cTnT was completely recovered in both groups 7 days after the race. In conclusion, cardiac damage occurs during a triathlon race and, is greater in elite than in non-elite. However, all cardiac damage markers return to normal range within 1 week.

Evolution of a dextransucrase gene for constitutive and hyper-production and for synthesis of new structure dextran

  • Gang, Hui-Gyeong;Kim, Do-Man;Jang, Seok-Sang
    • 한국생물공학회:학술대회논문집
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    • 2003.04a
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    • pp.545-549
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    • 2003
  • After irradiation of a cloned dextransucrase gene (dsrB742) with ultrasoft X-ray, an E. coli transformant (pDSRB742CK) was first developed for the expression of an extracellular dextransucrase, having increased activity and the synthesis of a highly branched dextran. Seven nucleotides of the parent gene (dsrB742) were changed in the nucleotide sequences of dsrB742ck. Among them, four nucleotides were changed at the ORF of dsrB742, resulting in a 30 amino acids deletion in the N-terminal of DSRB742 dextransucrase. The activity of DSRB742CK dextransucrase in culture supernatant was approximately 2.6 times higher (0.035 IU/ml) than that of the DSRB742 clone. The pDSRB742CK clone produced DSRB742CK dextransucrase when grown both on a sucrose medium (inducibly) and on a glucose medium (constitutively). The DSRB742 clone did not produce dextran constitutively on a glucose medium. DSRB742CK dextran had 15.6% branching and 2.7-times higher resistance to dextranase hydrolysis compared to DSRB742 dextran. $^{13}C-NMR$ showed that DSRB742CK dextran contained ${\alpha}-(1{\rightarrow}3)$ branch linkages that were not present in DSRB742 dextran.

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Protein Kinase CK2 Is Upregulated by Calorie Restriction and Induces Autophagy

  • Park, Jeong-Woo;Jeong, Jihyeon;Bae, Young-Seuk
    • Molecules and Cells
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    • v.45 no.3
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    • pp.112-121
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    • 2022
  • Calorie restriction (CR) and the activation of autophagy extend healthspan by delaying the onset of age-associated diseases in most living organisms. Because protein kinase CK2 (CK2) downregulation induces cellular senescence and nematode aging, we investigated CK2's role in CR and autophagy. This study indicated that CR upregulated CK2's expression, thereby causing SIRT1 and AMP-activated protein kinase (AMPK) activation. CK2α overexpression, including antisense inhibitors of miR-186, miR-216b, miR-337-3p, and miR-760, stimulated autophagy initiation and nucleation markers (increase in ATG5, ATG7, LC3BII, beclin-1, and Ulk1, and decrease in SQSTM1/p62). The SIRT1 deacetylase, AKT, mammalian target of rapamycin (mTOR), AMPK, and forkhead homeobox type O (FoxO) 3a were involved in CK2-mediated autophagy. The treatment with the AKT inhibitor triciribine, the AMPK activator AICAR, or the SIRT1 activator resveratrol rescued a reduction in the expression of lgg-1 (the Caenorhabditis elegans ortholog of LC3B), bec1 (the C. elegans ortholog of beclin-1), and unc-51 (the C. elegans ortholog of Ulk1), mediated by kin-10 (the C. elegans ortholog of CK2β) knockdown in nematodes. Thus, this study indicated that CK2 acted as a positive regulator in CR and autophagy, thereby suggesting that these four miRs' antisense inhibitors can be used as CR mimetics or autophagy inducers.

Expression of CD133, CD44, CK7, and OCT4 in Animal Cancers

  • Park, Jong-Ho;Cho, Eun-Sang;Ryu, Si-Yun;Jung, Ju-Young;Son, Hwa-Young
    • Korean Journal of Veterinary Research
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    • v.53 no.2
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    • pp.109-115
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    • 2013
  • Cancers are mainly sustained by a small pool of neoplastic cells, known as cancer stem cells or tumorinitiating cells. These cells possess the ability to self-renew and proliferate, and are thus able to form the tumor. In the present study cells that correspond to cancer stem cells in mammary and liver cancers in animals were identified by the expression of CD133, CD44, CK7, and OCT4 using immunochemistry. As a result, we found with CD133+ and CD44+ cancer stem cell-like phenotypes in mouse and canine hepatocellular carcinoma and canine mammary gland tumors. However, CK7+ and OCT4+ cells were not identified in animal mammary and liver cancer. CD133+ and CD44+ cells are wellknown stem cell lines and play key roles in development and metastasis in human cancer. These findings suggest that cancer stem cells are involved in animal tumorigenesis and may provide insight into mechanisms in cancer development as well as cancer diagnostics.

Extending shelf-life of Oriental Melon(Cucumis melo L.) by Modified Atmosphere Packaging (MA 포장기법에 의한 참외의 신선도 유지)

  • Park, Jong-Dae;Hong, Seok-In;Park, Hyung-Woo;Kim, Dong-Man
    • Korean Journal of Food Science and Technology
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    • v.32 no.3
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    • pp.481-490
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    • 2000
  • Modified atmosphere packaging was applied to oriental melon(Cucumis melo L. var. makuwa Mak.) to extend its freshness during distribution. Gas composition and ethylene content in the film bags changed rapidly at the early stage of storage. Within 10 days, weight loss of the unpackaged increased upto 7.68% while those of the packaged remained less than 1.0% except LDPE film modified by addition of 5%(w/w) zeolite with $20\;{\mu}m$ thickness(20CK, 2.38%). Firmness was effectively maintained in the LDPE film modified by addition of 5%(w/w) zeolite with $40\;{\mu}m$ thickness(40CK) and the LDPE film with $40\;{\mu}m$ thickness containing ethylene absorber sachet(40LP). Peel color of the fruit changed rapidly in control and a little in 40CK. Oriental melon packages using 40CK provided better visual and sensory quality retention compared with others. Results suggested that packaging treatment such as 40CK could be used for extending freshness of oriental melon during transport period at ambient temperature.

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A rare ginsenoside compound K (CK) induces apoptosis for breast cancer cells

  • Seun Eui Kim;Myoung-Hoon Lee;Hye-Myoung Jang;Wan-Taek Im;Joontaik Lee;Sang-Hwan Kim;Gwang Joo Jeon
    • Journal of Animal Reproduction and Biotechnology
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    • v.38 no.3
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    • pp.167-176
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    • 2023
  • Background: A breast cancer is the second leading cause of cancer death in women worldwide and among different types of breast cancers, triple-negative breast cancer (TNBC) has a poor prognosis. Methods: We investigated the potential of ginsenoside compound K (CK), an active ingredient in the bio-transformed ginsenoside, to be used as a therapeutic ingredient by examining the effects of CK on cell proliferation, apoptosis, and cancer-related gene expressions in breast cancer cells. Results: From the results of treating MCF-7, an ER and PR-positive breast cancer cells, and MDA-MB-231 (TNBC) with CK at a concentration of 0-100 µM, the half maximal inhibitory concentration (IC50) values for each cell were 52.17 µM and 29.88 µM, respectively. And also, it was confirmed that cell migration was inhibited above the IC50 concentration. In addition, fluorescence analysis of Apoptosis/Necrosis showed that CK induced apoptosis rather than necrosis of breast cancer cells. Through qPCR, it was confirmed that the expression of genes related to apoptosis and cell cycle arrest was increased in CK-treated breast cancer cells, and it acted more effectively on TNBC. However, the expression of genes related to tumor invasion and metastasis is also increased, so it is necessary to consider the timing of application of CK as a potential therapeutic anticancer compound. Conclusions: CK showed a stronger inhibitory effect in TNBC with poor prognosis but considering the high tumor invasion and metastasis-related gene expression, the timing of application of CK should be considered.