• 제목/요약/키워드: cell apoptosis

검색결과 4,235건 처리시간 0.037초

배양심근세포의 산화적 손상에 대한 사물탕의 방어효과 (Protective Effects of Samul-tang on Oxidative Stress induced Death of H9c2 Cardioblast Cells)

  • 조권일;정승원;장재호;이대용;박세욱;이인;신선호;문병순
    • 대한한의학회지
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    • 제26권1호
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    • pp.174-186
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    • 2005
  • Objectives : The water extract of Samul-tang (SMT) has traditionally been used for treatment of ischemic heart and brain damage in oriental medicine. However, little is known about the mechanism by which the water extract of SMT rescues cells from these damages. Methods: This study was designed to investigate the protective mechanisms of SMT on oxidative stress-induced toxicity in H9c2 cardiomyoblast cells. Treatment with $H_2O_2$ markedly induced death of H9c2 cardiomyoblast cells in a dose-dependent manner. Results: The characteristics of H20z-induced death of H9c2 showed apparent apoptotic features such as DNA fragmentation and morphological change. However, SMT significantly reduced both H202-induced cell death and morphological change. The decrease of Bc-2 expression by High were inhibited by SMT. In addition, the increase of Bax expression was also inhibited by SMT. The cotreatment of SMT and $H_2O_2$ in H9c2 cells also induced the phosphorylation of ERK in a time-dependent manner. Moreover, PD98059, a specific inhibitor of ERK1/2 attenuated the protective effects of SMT on $H_2O_2-induced$ toxicity in H9c2 cardiomyoblast cells. These results suggest that both ERK1/2 signaling pathways play important roles in the protective effects of SMT on $H_2O_2-induced$ apoptotic death of H9c2 cells. Also, the expression profile of proteins in $H_2O_2$ cardiomyoblast cells were screened by using two-dimensional (2-D) gel electrophoresis. Among 300 spots resolved in 2-D gels, the comparison of control versus apoptosis cells revealed that signal intensity of 17 spots increased and 11 spots decreased. Conclusions: Taken together, this study suggests that the protectiw effects of the water extract of SMT against oxidative damages may be mediated by the modulation of Bc1-2 and Bax expression via the regulation of the ERK signaling pathway.

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한국인 위암에서 KLF6 단백 발현 양상 (Expression Pattern of KLF6 in Korean Gastric Cancers)

  • 조용구;김창재;박조현;김수영;남석우;이석형;유남진;이정용;박원상
    • Journal of Gastric Cancer
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    • 제5권1호
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    • pp.34-39
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    • 2005
  • 목적: KLF6는 모든 조직에서 발현되고 있는 zinc finger를 가진 종양억제유전자로 인체 여러 암에서 불활성화되어 있다. 연구자들은 KLF6 단백의 발현 변화가 위암의 발생에 관여하는 지를 알아보고자 하였다. 대상 및 방법: 85예의 파라핀 포매된 위암조직에서 암세포들으 각각 3군데에서 펀치하여 새로운 파라핀 블록으로 옮겨 위암의 tissue microarray를 제작하였다. Tissue microarray 절편에서 KLF6 단백에 대한 항체로 면역화학염색을 실시한 후 발현 양상을 병리 지표들인 조직학적 소견, 침습 정도, 림프절 전이 및 복막파종 등과의 연관성을 조사하였다. 결과: KLF6 단백은 위점막의 표면과 소와 상피세포에서 주로 발현되고 있었고 85예 중 28예($28.9\%$)에서 발현 소실이 관찰되었다. 흥미롭게도 KLF6 단백의 발현 소실은 림프절 전이와 통계적으로 연관성이 있었으나 조직학적 소견, 침습 정도와 복막파종과는 연관성이 없었다. 결론: 이러한 소견들은 KLF6 단백의 발현 소실이 위장관 상피세포의 비정상적인 성장과 분화를 유도하고 위암의 발생 및 진행에 관여한다는 것을 의미한다.

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위상피이형성과 위암종에서 FasL의 발현 및 Apoptosis에 관한 연구 (Study of the Expression of FasL and of Apoptosis in Gastric Epithelial Dysplasia and Gastric Adenocarcinomas)

  • 박건욱;한상영;이종훈;금동주;노명환;최석렬;김종성;노미숙
    • Journal of Gastric Cancer
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    • 제1권2호
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    • pp.83-91
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    • 2001
  • Purpose: This study was to observe whether the apoptotic function of tumor-infiltrating lymphocytes (TIL) is induced in human gastric epithelial dysplasia and gastric adenocarcinoma according to the role of FasL expression. Materials and Methods: A total of 56 gastric epithelial dysplasia and gastric adenocarcinoma patients were enrolled in this study: 9 cases of gastric epithelial dysplasia, 18 cases of early gastric carcinomas (EGC) and 29 cases of advanced gastric carcinomas (AGC). Immunohistochemical staining was performed for FasL and CD45, and the terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) method was used to detect cell death in tumor-infiltrating lymphocytes. Results: 1) Positive reactions of FasL to neoplastic cells were $88.9\%$ (8/9) in gastric epithelial dysplasia, $83.3\%$ (15/18) in EGC, and $75.9\%$ (22/29) in AGC. 2) Expression of TIL was decreased in the FasL positive region and was increased in the FasL negative region, and significant expression of TIL was observed in the AGC group (P=0.001). 3) Expression of apoptotic TIL was very similar to the FasL expression, and $100\%$ expression was observed in gastric epithelial dysplasia group. 4) Expression of apoptotic TIL was increased in the FasL positive region and decreased in the FasL negative region, and significant apoptotic expression was observed in the gastric epithelial dysplasia and EGC groups (P=0.0420, P=0.0263, respectively). Conclusion: These results suggest that FasL is a prevalent mediator of immune privilege in epithelial dysplasia and cancer of the stomach.

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Ellagic acid가 대식세포의 면역조절작용에 미치는 영향과 Toll-like receptor 4 관련 작용기전 연구 (Study on the Immunomodulatory Effects of Ellagic Acid and their Mechanisms Related to Toll-like Receptor 4 in Macrophages)

  • 남궁승;김예진;김태성;손은화
    • 한국자원식물학회지
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    • 제25권5호
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    • pp.561-567
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    • 2012
  • 본 연구는 EA에 의한 대식세포의 활성화를 매개로 한 항암효과와 항암작용과 관련된 대식세포의 면역조절효과를 확인하였다. 연구 결과 EA에 의해 RAW264.7세포 및 peritoneal macrophage 모두에서 항암효과가 증가하였으며, 증가된 대식세포의 항암효과는 TLR4 signaling을 blocking하는 CLI-095을 함께 처리하였을 때 일부 감소되었다. 이는 EA에 의한 항암 효과가 부분적으로 TLR4를 경유하는 기전으로 나타나는 것을 의미한다. 또한, EA에 대한 대식세포의 NO 분비조절효과를 측정하였으며, EA는 대식세포의 NO 생성을 증가시켰으나, 인위적으로 염증을 유발시켜 NO를 과도하게 분비한 상태에서는 NO 분비를 오히려 억제시키는 결과를 나타내었다. 이와 같이 EA에 의한 NO조절에 대한 이중 효과는 인체에 면역증강과 항염증 효과라는 긍정적인 효과를 나타내는 방향으로 조절하고 있으므로 EA를 이용한 항암요법의 보조제 및 면역보조제로써의 활용에 유익할 것으로 사료된다. 향후 EA에 대한 항암 작용 및 NO 조절에서 세포내 신호전달 작용기전에 대한 심도 있는 연구가 진행되어야 할 것으로 보인다.

직자(直刺), 영수(迎隨) 및 염전수기법(捻轉手技法)에 따라 시행한 경거(經渠)${\cdot}$복류(復溜) 침자(鍼刺)가 중대뇌동맥(中大腦動脈) 폐새(閉塞)에 의하여 유발(誘發)된 국소(局所) 뇌허혈(腦虛血) 백서(白鼠) hippocampus의 항세포자멸사(抗細胞自滅死) 및 복경보호(福經保護)에 미치는 영향(影響) (Effects of acupuncture at the $LU8{\cdot}K17$ on Anti-apoptotic cell death and neuroprotection in Rat hippocampus following focal brain ischemic injury induced by Intraluminal Filament insertion in Rats)

  • 윤대환;변정윤;최찬헌;백진웅;정지연;정연진;나창수
    • Korean Journal of Acupuncture
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    • 제24권3호
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    • pp.205-221
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    • 2007
  • Objectives : Aims of this study is to investigate the effects of $LU8{\cdot}KI7$ in rat induced by experimental focal ischemia. Materials and methods : The focal ischemia was induced by intraluminal filament insertion into middle cerebral artery. The groups divided into 6groups, control; no therapy group after ischemia-induced, AT1; acupuncture therapy group at $LU8{\cdot}KI7$ after ischemia-induced, AT2; acupuncture therapy at $LU8{\cdot}KI7$ bilaterally and the needle was twirled and rotated forward with the thumb of the right hand 9times, AT3; acupuncture therapy at $LU8{\cdot}KI7$ bilaterally and the needle was twirled and rotated forward with the forefinger of the right hand 9times, AT4; acupuncture therapy at$LU8{\cdot}KI7$ bilaterally and the needle was inserted to the direction following the flowing route of the meridian(digital direction), AT5; acupuncture therapy at $LU8{\cdot}KI7$ bilaterally, the needle was inserted to the direction following the flowing route of the meridian(digital direction) and the needle was twirled and rotated forward with the thumb of the right hand 9times. Acupuncture therapy was carried out 7times during 2weeks after focal ischemia-induced. The anti-apoptotic and neuroprotective effects of acupuncture are observed by Bax, Bcl-2, mGluR5, cytochrome c, Cresyl violet and ChAT-stain. Results : The intensity of Bax was decreased in AC1, AC4, AC5 group, was increased in AC2, AC3 group. The intensity of Bcl-2 was increased in AC2, AC3, AC4, AC5 group. The intensity of mGluR5 was decreased in AC1 group, was increased in AC4, AC5 group. The intensity of Cytochrome c was increased in ACI, AC2 group, was decreased in AC4, AC5 group. The density of neurons stained by Cresyl violet was increased in all group without control group. The density of ChAT was increased in AC2, ACS group. Conclusions : Our study suggests that AC5 group show anti-apoptotic and neuroprotective effects on cholinergic neuron in focal cerebral ischemia of the stroke in rats.

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인간 전립선암세포에 있어서 칼슘조절을 통한 mifepristone의 세포독성효과 (Cytotoxicity of Mifepristone via Calcium Modulation In Human Prostate Cancer Cells)

  • 송휘준;김병기
    • 생명과학회지
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    • 제19권7호
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    • pp.892-898
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    • 2009
  • Mifepristone (MIF)은 프로게스테론 유사체이며, 강한 항프로게스테론 효과 때문에 전립선암 치료에 사용되고 있다. 본 연구에서는 MIF의 세포독성효과가 세포 내 칼슘농도 조절에 의한 것임을 밝힌다. 5-40 $\mu$M의 MIF를 처리 시 LNCaP 전립선암세포의 성장이 농도와 시간의존적으로 감소하였다. 반대로, 세포 내 칼슘의 레벨은 MIF의 처리시간과 농도도 의존적으로 증가하였다. MIF를 처리한 세포를 PI 혹은 Hoechst로 염색한 결과, 전형적인 세포자살의 징후인 응축된 염색질과 핵 조각단편들이 관찰되었다. 이들 세포자살징후 역시 MIF의 처리시간과 농도가 증가 할수록 심화되었다. 세포자살에 직접적으로 관여하는 중요한 단백질인 Bcl-2 그룹 단백질의 발현을 조사해 본 결과, 세포자살 억제단백질인 Bcl-2의 발현은 MIF처리시 치명적으로감소하였고, 대신에 세포자살 촉진단백질인 Bax의 발현은 2배로 증대되었다. 이상의 결과로 보아 MIF의 세포독성효과는 세포 내의 칼슘조절에 따른 세포자살에 의한 것으로 생각된다.

한우 육질등급이 난포란의 배반포 체외생산에 미치는 영향 (Correlation of Hanwoo (Korean Native Cattle) Carcass Classification and Oocyte Donor for Blastocyst Production In Vitro)

  • 김강식;이홍철;박용수;김소섭;박흠대
    • 한국수정란이식학회지
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    • 제30권3호
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    • pp.161-170
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    • 2015
  • These studies were conducted to establish the practical Hanwoo (Korean native cattle) improvement system through the combining of embryo transfer technology and confirming individual Hanwoo oocyte culture system and to investigate that correlation of Hanwoo carcass classification (intramuscular marbling) and oocyte donor for blastocyst production in vitro. In case of Hanwoo, the carcass meat quality grades were divided to grade $1^{{+}{+}}$, $1^{+}$, 1, 2, and 3 depends on fat distribution of longest muscle cross-sectional surface. As results, the numbers of follicular oocytes collected from individual fundamentally-registered Hanwoo yielded $1^{{+}{+}}$, $1^{+}$, 1, 2 and 3 meat quality were 9.5, 9.4, 8.5, 8.8 and 8.8 per ovary, respectively. The numbers of retrieval oocyte from follicles were significantly higher in the cattle yield $1^{{+}{+}}$, $1^{+}$ meat quality than in the cattle yield 1, 2 and 3 meat quality (p<0.05). The rates of blastocyst formation were 18.2, 21.3, 29.4, 30.9, and 31.5% in the cattle yield $1^{{+}{+}}$, $1^{+}$, 1, 2 and 3 meat quality of after in vitro maturation, respectively. It was significantly lower in the cattle yield $^{{+}{+}}$ and $1^{+}$ meat quality than in the cattle yield 1, 2 and 3 meat quality (p<0.05). In order to evaluate embryos quality, TUNNEL assay was conducted for each meat quality grade using blastocyst stage embryo on day 8. The results showed that apoptosis cell number was higher tendency in the cattle yield $1^{{+}{+}}$and $1^{+}$ meat quality (81 and 79, respectively) than in the cattle yield 1, 2 and 3 meat quality (51, 48 and 50, respectively) but there was no statistical significance in each group. After embryo transfer, the conception rate of recipient was 53.5 (23 out of 43), 52.1 (38 out of 73) and 58.0% (58 out of 100) in the meat quality of 1, $1^{+}$ and $1^{{+}{+}}$, respectively. These results showed that the conception rate was significantly higher in the cattle yield 1 meat quality than in the cattle yield $1^{{+}{+}}$, $1^{+}$, 2, and 3 meat quality (p<0.05). In summary, these results indicate that the application of confirming Hanwoo individual oocyte culture system and embryo transfer technology can make good use of the genetic resources conservation and improvement of Hanwoo. Relevance of the meat quality grade and reproductive ability of carcasses of Hanwoo will be considered to be one of the effective means for the associated research with obesity and reproduction.

Therapeutic Benefits of Mesenchymal Stromal Cells in a Rat Model of Hemoglobin-Induced Hypertensive Intracerebral Hemorrhage

  • Ding, Rui;Lin, Chunnan;Wei, ShanShan;Zhang, Naichong;Tang, Liangang;Lin, Yumao;Chen, Zhijun;Xie, Teng;Chen, XiaoWei;Feng, Yu;Wu, LiHua
    • Molecules and Cells
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    • 제40권2호
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    • pp.133-142
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    • 2017
  • Previous studies have shown that bone marrow mesenchymal stromal cell (MSC) transplantation significantly improves the recovery of neurological function in a rat model of intracerebral hemorrhage. Potential repair mechanisms involve anti-inflammation, anti-apoptosis and angiogenesis. However, few studies have focused on the effects of MSCs on inducible nitric oxide synthase (iNOS) expression and subsequent peroxynitrite formation after hypertensive intracerebral hemorrhage (HICH). In this study, MSCs were transplanted intracerebrally into rats 6 hours after HICH. The modified neurological severity score and the modified limb placing test were used to measure behavioral outcomes. Blood-brain barrier disruption and neuronal loss were measured by zonula occludens-1 (ZO-1) and neuronal nucleus (NeuN) expression, respectively. Concomitant edema formation was evaluated by H&E staining and brain water content. The effect of MSCs treatment on neuroinflammation was analyzed by immunohistochemical analysis or polymerase chain reaction of CD68, Iba1, iNOS expression and subsequent peroxynitrite formation, and by an enzyme-linked immunosorbent assay of pro-inflammatory factors (IL-$1{\beta}$ and TNF-${\alpha}$). The MSCs-treated HICH group showed better performance on behavioral scores and lower brain water content compared to controls. Moreover, the MSC injection increased NeuN and ZO-1 expression measured by immunochemistry/immunofluorescence. Furthermore, MSCs reduced not only levels of CD68, Iba1 and pro-inflammatory factors, but it also inhibited iNOS expression and peroxynitrite formation in perihematomal regions. The results suggest that intracerebral administration of MSCs accelerates neurological function recovery in HICH rats. This may result from the ability of MSCs to suppress inflammation, at least in part, by inhibiting iNOS expression and subsequent peroxynitrite formation.

암종양유전자 SETDB1과 FosB 발현에 대한 p53의 음성 조절기작 (Negative Regulation of Tumor Suppressor p53 at the Promoter Regions of Oncogenic SETDB1 and FosB Genes)

  • 윤현지;나한흠;김근철
    • 생명과학회지
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    • 제30권12호
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    • pp.1070-1077
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    • 2020
  • 암세포에 항암제를 처리하게 되면, 세포증식, 이동성 또는 약물 내성과 관련된 많은 유전자들의 발현 변화가 발생하며, 유전자 발현 변화는 상호간의 조절 네트워크에 의해 밀접하게 연결될 수도 있다고 추측된다. 본 연구에서 p53 유전자 유무가 다른 A549와 H1299 인간 폐암세포에 독소루비신을 처리하면, 원종양유전자인 FosB의 발현은 증가하지만, 원종양유전자인 SETDB1의 발현은 감소하지만, 단백질 발현의 양적인 차이가 발생한다는 사실을 알 수 있었다. TF motif binding 분석 프로그램을 이용하여 SETDB1과 FosB 프로모터지역에서의 p53단백질의 결합가능성을 분석한 결과, SETDB1의 경우 18부위, FosB의 경우 21 부위의 p53 결합부위를 예측할 수 있었다. SETDB1과 FosB 프로모터의 subcloning하여 luciferase 분석을 수행한 결과, p53은 SETDB1과 FosB을 음성적으로 조절한다는 사실을 알 수 있었다. 또한, H1299 세포에 p53의 과발현은 SETDB1 과 FosB의 발현을 감소시킬 수 있음을 RT-PCR, western blot, qPCR, 면역염색 실험을 통해 확인하였다. 이러한 결과를 종합하여 본다면, p53에 의한 SETDB1과 FosB 유전자 발현 조절은 항암제 처리과정에서 나타나는 암세포의 사멸과 생존에 대한 기능적 조절 네트워크로 사료된다.

The antioxidant icariin protects porcine oocytes from age-related damage in vitro

  • Yoon, Jae-Wook;Lee, Seung-Eun;Park, Yun-Gwi;Kim, Won-Jae;Park, Hyo-Jin;Park, Chan-Oh;Kim, So-Hee;Oh, Seung-Hwan;Lee, Do-Geon;Pyeon, Da-Bin;Kim, Eun-Young;Park, Se-Pill
    • Animal Bioscience
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    • 제34권4호
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    • pp.546-557
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    • 2021
  • Objective: If fertilization does not occur within a specific period, the quality of unfertilized oocytes in the oviduct (in vivo aging) or in culture (in vitro aging) will deteriorate over time. Icariin (ICA), found in all species of Epimedium herbs, has strong antioxidant activity, and is thought to exert anti-aging effects in vitro. We asked whether ICA protects oocytes against age-related changes in vitro. Methods: We analyzed the reactive oxygen species (ROS) levels and expression of antioxidant, maternal, and estrogen receptor genes, and along with spindle morphology, and the developmental competence and quality of embryos in the presence and absence of ICA. Results: Treatment with 5 μM ICA (ICA-5) led to a significant reduction in ROS activity, but increased mRNA expression of glutathione and antioxidant genes (superoxide dismutase 1 [SOD1], SOD2, peroxiredoxin 5, and nuclear factor erythroid 2-like 2), during aging in vitro. In addition, ICA-5 prevented defects in spindle formation and chromosomal alignment, and increased mRNA expression of cytoplasmic maturation factor genes (bone morphogenetic protein 15, cyclin B1, MOS proto-oncogene, serine/threonine kinase, and growth differentiation factor-9). It also prevented apoptosis, increased mRNA expression of antiapoptotic genes (BCL2-like 1 and baculoviral IAP repeat-containing 5), and reduced mRNA expression of pro-apoptotic genes (BCL2 antagonist/killer 1 and activation of caspase-3). Although the maturation and cleavage rates were similar in all groups, the total cell number per blastocyst and the percentage of apoptotic cells at the blastocyst stage were higher and lower, respectively, in the control and ICA-5 groups than in the aging group. Conclusion: ICA protects oocytes against damage during aging in vitro; therefore, it can be used to improve assisted reproductive technologies.