• 제목/요약/키워드: p53 activation

검색결과 321건 처리시간 0.025초

언어영역의 기능적 자기공명영상 (Functional MRI of Language Area)

  • 유재욱;나동규;변홍식;노덕우;조재민;문찬홍;나덕렬;장기현
    • Investigative Magnetic Resonance Imaging
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    • 제3권1호
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    • pp.53-59
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    • 1999
  • 목적 : 언어기능의 지도화(language mapping) 및 우세반구 결정에 있어서 기능적 자기공명영상의 유용서을 알아보고자 하였다. 대상 및 방법 : 자원자 10명(남자 6명, 여자 4명, 오른손잡이 7명, 왼손잡이 3명)을 대상으로 단어생성 과제(명사만들기, 동사만들기)와 판단과제를 이용하여 언어영역의 활성화를 유도하였다. 1.5T 초진도 자기공명영상장치에서 EPI로 BOLD 기법을 이용하여 기능적 영상을 얻었으며, 여앙후처리는 SPM 분석 프로그램을 이용하였다. 기능적 영상은 2번의 활성기와 3번의 휴식기를 번갈아 시행하였고 스캔 시간은 각각30초였으며 총 영상획득시간은 162초였다. 유의수준 p<0.001을 기준ㅇ로 자극 과제에 따라 활성화된 뇌영역을 분석하였고 반구별로 활성화된 화소의 수를 측정하여 편재화지수(lateralization index)를 구하였다. 결과 : 왼손잡이 1명을 제외한 9명에서 성공적으로 기능적 영상을 얻었으며 양측 전운동영역(premotor area), 하전두회, 두정엽, 중측두회 등의 여러 영역에서 활성화 신호가 나타났다. 오른손잡이의 경우 편재화지수는 평균 0,64(0.16~1)로 모두 좌측으로 편재화 되었다. 과제별로는 동사만들기 과제가 명사만들기 및 판단 과제에 비해 언어 영역의 활성화가 많았고 편재화지수의 값도 높았다. 결론 : 기능적 자기공명영상은 언어영역의 뇌기능지도화 및 우세반구 결저에 있어서 유용한 검사 방법이 될 수 있으리라 생각된다.

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1,3-Dichloro-2-Propanol (1,3-DCP)에 의한 세포의 손상기전 (1,3-Dichloro-2-Propanol (1,3-DCP) Induced Cell Damage)

  • 정지학;신익재;신영민;박흥재;안원근
    • 한국환경과학회지
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    • 제16권2호
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    • pp.219-225
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    • 2007
  • Endocrine disrupting compounds (EDC's) are chemicals that either mimic endogenous hormones interfering with pharmacokinetics or act by other mechanisms. Some endocrine disrupters were reported to be chemical substances that cause apoptosis in cells. A number of reports have indicated that 1,3-DCP, one of the EDC's may act as an endocrine disrupter and also has possible carcinogenic effects. 1,3-DCP, present in commercial protein hydrolysates used for human nutrition, are genotoxic and 1,3-dichloro-2-propanol induced tumors in rats. In the present study, it was investigated whether 1,3-DCP induces ROS generation and apotosis in A549 adenocarcinoma cells. Here we show that 1,3-DCP inhibits the growth of lung cancer cell lines and generates reactive oxygen species (ROS), a major cause of DNA damage and genetic instability, It was investigated that 1,3-DCP increases G1 phase cells after 12 hours, thereafter abruptly draws A549 cells to G0 state after 24 hours by flow cytometric analysis. 1,3-DCP induces p53 and $p21^{Cip1/WAF1}$ activation time- and dose-dependently by 24 hours, while the level $p21^{Cip1/WAF1}$ was decreased after 48 hours. These results suggest that 1,3-DCP, an EDC's generates ROS and regulates genes involved with cell cycle and apoptosis.

The Role of Kif4A in Doxorubicin-Induced Apoptosis in Breast Cancer Cells

  • Wang, Hui;Lu, Changqing;Li, Qing;Xie, Jun;Chen, Tongbing;Tan, Yan;Wu, Changping;Jiang, Jingting
    • Molecules and Cells
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    • 제37권11호
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    • pp.812-818
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    • 2014
  • This study was to investigate the mechanism and role of Kif4A in doxorubicin-induced apoptosis in breast cancer. Using two human breast cancer cell lines MCF-7 (with wild-type p53) and MDA-MB-231 (with mutant p53), we quantitated the expression levels of kinesin super-family protein 4A (Kif4A) and poly (ADP-ribose) Polymerase-1 (PARP-1) by Western blot after doxorubicin treatment and examined the apoptosis by flow cytometry after treatment with doxorubicin and PARP-1 inhibitor, 3-Aminobenzamide (3-ABA). Our results showed that doxorubicin treatment could induce the apoptosis of MCF-7 and MDA-MB-231 cells, the down-regulation of Kif4A and upregulation of poly(ADP-ribose) (PAR). The activity of PARP-1 or PARP-1 activation was significantly elevated by doxorubicin treatment in dose- and time-dependent manners (P < 0.05), while doxorubicin treatment only slightly elevated the level of cleaved fragments of PARP-1 (P > 0.05). We further demonstrated that overexpression of Kif4A could reduce the level of PAR and significantly increase apoptosis. The effect of doxorubicin on apoptosis was more profound in MCF-7 cells compared with MDA-MB-231 cells (P < 0.05). Taken together, our results suggest that the novel role of Kif4A in doxorubicin-induced apoptosis in breast cancer cells is achieved by inhibiting the activity of PARP-1.

Inhibition of $NF-{\kappa}B$ Activation Increases Oxygen-Glucose Deprivation-Induced Cerebral Endothelial Cell Death

  • Lee, Jin-U;Kim, Chul-Hoon;Shim, Kyu-Dae;Ahn, Young-Soo
    • The Korean Journal of Physiology and Pharmacology
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    • 제7권2호
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    • pp.65-71
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    • 2003
  • Increasing evidences suggest that ischemia-induced vascular damage is an integral step in the cascade of the cellular and molecular events initiated by cerebral ischemia. In the present study, employing a mouse brain endothelioma-derived cell line, bEnd.3, and oxygen-glucose deprivation (OGD) as an in vitro stroke model, the role of nuclear factor kappa B (NF-${\kappa}B$) activation during ischemic injury was investigated. OGD was found to activate NF-${\kappa}B$ and to induce bEnd.3 cell death in a time-dependent manner. OGD phosphorylated neither 32 Ser nor 42 Tyr of $I{\kappa}B{\alpha}$. OGD did not change the amount of $I{\kappa}B{\alpha}$. The extents of OGD-induced cell death after 8 h, 10 h, 12 h and 14 h of OGD were 10%, 35%, 60% and 85%, respectively. Reperfusion following OGD did not cause additional cell death, indicating no reperfusion injury after ischemic insult in cerebral endothelial cells. Three known as NF-${\kappa}B$ inhibitors, including pyrrolidine dithiocarbamate (PDTC) plus zinc, aspirin and caffeic acid phenethyl ester (CAPE), inhibited OGD-induced NF-${\kappa}B$ activation and increased OGD-induced bEnd.3 cell death in a dose dependent manner. There were no changes in the protein levels of bcl-2, bax and p53 which are modulated by NF-${\kappa}B$ activity. These results suggest that NF-${\kappa}B$ activation might be a protective mechanism for OGD-induced cell death in bEnd.3.

탈핵 후 동결한 MII 난자의 활성화 시기가 체세포 핵치환 이후 소 난자의 체외발달에 미치는 영향 (In vitro Development of Somatic Cell Nuclear Transferred Bovine Embryos Following Activation Timing in Enucleated and Cryopreserved MII Oocytes)

  • 박세필;김은영;김선균;이영재;길광수;박세영;윤지연;이창현;정길생
    • 한국가축번식학회지
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    • 제26권3호
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    • pp.245-252
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    • 2002
  • 본 연구는 체세포 핵치환에 탈핵 후 통격한 소미수정란을 사용함에 있어서, MVC 초자화 동결방법과 탈핵난자의 활성화시기가 융해 후 생존율과 핵치환 이후 체외 발달에 미치는 영향을 조사하고자 실시하였다. 체외에서 20시간 동안 체외성숙된 소 미수정란은 수핵란으로 사용하기 위하여 5$\mu\textrm{g}$/$m\ell$ hoechst 처리 후, 형광현미경하에서 핵을 제거하였다. 본 실험은 세 그룹으로 나누어 실행되었다 Group I은 동결하지 않고 핵치환을 한 대조군이며, group III와 group II는 핵이 제거된 난자를 MVC 방법으로 동결하기 전과 후에 활성화 처리 (5$\mu\textrm{m}$의 ionomycin에 의해서 5분간 처리) 한 군이다. 초자화 동결을 위해서는 group II와 group III의 탈핵란은 EG10에서 5~10분간 전처리하고 EG30에서 30초간 노출하여 액체 질소에 침지하였다. 융해는 37$^{\circ}C$에서 4단계로 이루어졌다. 실험군은 모두 소 귀세포를 이용하여 핵치환을 실시하였으며, 전핵을 유도하기 위한 활성화를 위해서는 10$\mu\textrm{g}$/$m\ell$ cycloheximide와 2.5$\mu\textrm{g}$/$m\ell$ cytochalasin D)가 첨가된 CRlaa 배양액에서 1시간, 이후 10 $\mu\textrm{g}$/$m\ell$ cycloheximide가 들어있는 CRlaa 배양액에서 4시간동안 배양하였다. 활성화 처리가 끝난 난자들은 CRlaa 배양액에서 2일간 배양하여 난할이 유도된 난자만을 선별하여 난구세포와 7일 동안 공배양하였다. 동결 융해 이후 group II와 group III의 탈핵된 소 미수정란의 체외 생존율은 81.0%와 84.9%로 유의적인 차이가 없었다. 체세포와 수핵란과의 융합율도 각각 69.0%와 70.0%로 대조군 (75.2%) 과도 유의적인 차이를 나타내지 않았다. 난할율은 53.4%와 58.4%로 group II와 group III간에 유의적인 차이를 나타내지 않았지만 group II의 분할된 세포질을 가진 이상난자의 비율이 group III보다 유의하게 높게 나타났다 (P<0.05). 또한, morula 이상으로 발달율도 group II (8.6%) 에서 group III (15.6%)보다 낮은 결과를 얻었다 하지 만 group III (15.6%)의 체외 발달율은 대조군 (24.8%)과 유의한 차이를 없었다. 따라서, MVC 동결 방법은 탈핵된 소 미수정란을 동결하기에 적합한 방법이며, 탈핵 후 activation을 유도하고 초자화 동결한 난자는 동결하지 않은 신선란과 동일하게 체세포 핵치환에 유용하게 이용될 수 있으리라 사료된다.

베개 높이에 따른 SCM과 Upper trapezius의 근 두께, 근 긴장도, 근 활성화 측정비교 (Comparison of Thickness, Tension, and Activation of the Scm and Upper Trapezius Muscles According To The Pillow Height)

  • 김은미;박민지;유은정;이동엽;홍지헌;유재호;김진섭;남연교;김성길
    • 대한물리의학회지
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    • 제19권1호
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    • pp.53-60
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    • 2024
  • PURPOSE: The study aimed to analyze the effect of pillow height on upper trapezius and sternocleidomastoid (SCM) muscle activity and overall human body comfort to determine the optimal pillow height. METHODS: The study included 32 healthy college students, of both genders, who provided prior consent. It examined three pillow heights (flat, 6cm, 12cm) and measured the upper trapezius and SCM muscles using ultrasonography, myotone, and electromyography(EMG). Muscle activation, thickness, and fatigue were assessed. RESULTS: The study found significant differences in muscle thickness and muscle tone based on the pillow heights (flat, 6cm, and 12cm) with a p < .05. The SCM and upper trapezius muscles were thinnest at a pillow height of 6cm. Muscle tone in the SCM was lower at both 6cm and 12cm pillow heights. Post-hoc measurements showed significant differences in both the SCM and upper trapezius muscles thickness at the 6cm pillow height (p < .05). Also, significant differences in muscle tone were observed only in the SCM, particularly between the 6cm and 12cm pillow heights. CONCLUSION: The ultrasonography and myotone measurements showed a significant difference in muscle thickness and muscle tension, both of which were above 6cm, while there was no difference in muscle activation. Based on the strong correlation between muscle tension and muscle thickness with pillow height, this study concluded that the human body feels comfortable with a 6cm pillow height. Therefore, it is recommended to use a pillow height of 6cm when lying in a supine position.

인진(茵蔯)의 에탄올 추출물이 담도암 세포주 SNU-1196의 apoptosis에 미치는 효과에 관한 연구 (Study on the Pro-apoptotic Effect of Artemisiae Capillaris Herba Extracted with Ethanol on Biliary Tract Cancer Cell Line, SNU-1196)

  • 이경욱;우홍정
    • 대한한방내과학회지
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    • 제33권4호
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    • pp.587-598
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    • 2012
  • Objectives : This study was performed to elucidate the pro-apoptotic effect of Artemisiae capillaris herba extracted with ethanol on biliary tract cancer cells. Materials and Methods : The biliary tract cancer cell line SNU-1196 was used in this study. Cells were treated with different concentrations of Artemisiae capillaris herba for 24, 48 and 72 hours. After the treatment, cell viability, apoptosis, caspase activities and the mRNA expressions of the Bcl-2, Bax, P53, and P21 were measured by using MTT assay, cell cycle analysis, apoptosis assay, and RT-PCR. The cell cycle analysis was done by flow cytometry and apoptosis assay by cell death detection ELISA kit. Results : Artemisiae capillaris herba inhibited proliferation of SNU-1196 in long-time culture group with dose-dependent manner. All cells treated with Artemisiae capillaris herba showed increased apoptosis with dose- and time-dependent manner. Exposure of SNU-1196 to Artemisiae capillaris herba induced caspase-3 activation. However, apeoptosis was blocked when SNU-1196 was treated together with the pan-caspase inhibitor Z-VAD-FMK and the caspase-3 inhibitor Z-DEVE-FMK. After the treatment of Artemisiae capillaris herba, the mRNA expressions of caspase -3, -8, -9, p53, and p21 was increased in all cells. Artemisiae capillaris herba resulted in a significant decrease in Bcl-2 and an increase in Bax mRNA levels. Conclusions : These results suggest that Artemisiae capillaris herba would be beneficial in the treatment of biliary tract cancer.

천화분 약침액의 A549 폐암 세포주에서 apoptosis 유발효과 (The Induction Effect of Apoptosis in A549 Human Lung Cancer Cells by the Trichosanthes Kirilowii Pharmacopuncture Solution)

  • 최태연;이성원;류연희;반효정;서근영;김재효;안성훈;손인철
    • Korean Journal of Acupuncture
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    • 제27권4호
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    • pp.15-23
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    • 2010
  • Objectives : In order to confirm the anti-cancer effect of Trichosanthes kirilowii pharmacopuncture fluid, this study was proceeded. Methods : A549 lung cancer cells were cultured to be treated by Trichosanthes kirilowii pharmacopuncture fluid as dose dependent manner for 72 hours. And then the cell viability, nucleus fragmentaion, p21 and p53 protein expression, Bcl-2 and Bax protein expression, procaspase-3 PARP protein expression. Results : 1. Trichosanthes kirilowii pharmacopuncture fluid decrease A549 cell viability as dose dependent manner. 2. Trichosanthes kirilowii pharmacopuncture fluid induced the nucleus fragmentation in A549 lung cancer cells as dose dependent manner. 3. Trichosanthes kirilowii pharmacopuncture fluid increase the p21 and p53 protein expression. 4. Trichosanthes kirilowii pharmacopuncture fluid decrease the Bcl-2 protein expression but cannot affect the Bax protein expression. 5. Trichosanthes kirilowii pharmacopuncture fluid increase the activation of caspase-3 and PARP protein. Conclusions : As the above results, it was conclused the Trichosanthes kirilowii pharmacopuncture fluid had the anti-cancer effects to induce apoptosis.

Sinapic acid induces the expression of thermogenic signature genes and lipolysis through activation of PKA/CREB signaling in brown adipocytes

  • Hossain, Monir;Imran, Khan Mohammad;Rahman, Md. Shamim;Yoon, Dahyeon;Marimuthu, Vignesh;Kim, Yong-Sik
    • BMB Reports
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    • 제53권3호
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    • pp.142-147
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    • 2020
  • Lipid accumulation in white adipose tissue is the key contributor to the obesity and orchestrates numerous metabolic health problems such as type 2 diabetes, hypertension, atherosclerosis, and cancer. Nonetheless, the prevention and treatment of obesity are still inadequate. Recently, scientists found that brown adipose tissue (BAT) in adult humans has functions that are diametrically opposite to those of white adipose tissue and that BAT holds promise for a new strategy to counteract obesity. In this study, we evaluated the potential of sinapic acid (SA) to promote the thermogenic program and lipolysis in BAT. SA treatment of brown adipocytes induced the expression of brown-adipocyte activation-related genes such as Ucp1, Pgc-1α, and Prdm16. Furthermore, structural analysis and western blot revealed that SA upregulates protein kinase A (PKA) phosphorylation with competitive inhibition by a pan-PKA inhibitor, H89. SA binds to the adenosine triphosphate (ATP) site on the PKA catalytic subunit where H89 binds specifically. PKA-cat-α1 gene-silencing experiments confirmed that SA activates the thermogenic program via a mechanism involving PKA and cyclic AMP response element-binding protein (CREB) signaling. Moreover, SA treatment promoted lipolysis via a PKA/p38-mediated pathway. Our findings may allow us to open a new avenue of strategies against obesity and need further investigation.

다양한 각도의 경사로 횡단 조건에서 보행과 한발 서기 시 중둔근 활성도 (Gluteus Medius Muscle Activities According to Various Angle of Mediolateral Ramp During Cross Walking and One-leg Standing)

  • 김선칠;이상열
    • 대한물리의학회지
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    • 제12권2호
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    • pp.53-57
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    • 2017
  • PURPOSE: The purpose of study was to clear up the environmental risk factor that can be easily occurred unstability of hip during gait and one leg standing at various ramp angle. METHODS: Twenties healthy males of 69 subjects is participated in this study. Participants was measured activation on gluteus medius muscle during both conditions (walk across the ramp and one leg stand in the transverse direction) of seven different angle. The measured data were analyzed using one-way ANOVA to investigate the effect of muscle activation on the each condition. The statistical analyses were performed using SPSS ver. 18.0 and p-value less than .05 were considered significant for all cases. A post-hoc test was performed by Bonferoni method. RESULTS: The study showed that more muscle activities on gluteus medius is increased by increasing the ramp angle. Post-hoc analysis demonstrated that the peak and mean of muscle activity increased significantly with a ramp angle of $15^{\circ}$ and $25^{\circ}$ during gait and one-leg stand. CONCLUSION: According to the study results, impaired balance can be easily occurred when cross walk and one-leg stand on a ramp from higher than $15^{\circ}$, and highest risk was angle of $25^{\circ}$ or more. As a people with gluteus medius muscle weakness walks a ramp, the ramp angle has a cross relationship with the impaired balance. If people with gluteus medius weakness walk on the more than $10^{\circ}$ of ramp angle, they will need a lot of attention for prevent impaired balance.