• 제목/요약/키워드: Death receptor

검색결과 396건 처리시간 0.035초

The role of ginseng total saponin in transient receptor potential melastatin type 7 channels

  • Kim, Byung Joo
    • Animal cells and systems
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    • 제16권5호
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    • pp.376-384
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    • 2012
  • Although ginsenosides have a variety of physiologic or pharmacologic functions in various regions, there are only a few reports on the effects of transient receptor potential melastatin 7 (TRPM7) channels. Here, we showed evidence suggesting that TRPM7 channels play an important role in ginseng total saponin (GTS)-mediated cellular injury. The combination techniques of electrophysiology, pharmacological analysis, small interfering RNA (siRNA) method and cell death assays were used. GTS depolarized the resting membrane potentials and decreased the amplitude of pacemaker potentials in cultured interstitial cells of Cajal (ICCs) in gastrointestinal (GI) tract. The TRPM7-like currents in single ICCs and the overexpressing TRPM7 in HEK293 cells were inhibited by GTS. However, GTS had no effect on $Ca^{2+}$-activated $Cl^-$ conductance. GTS inhibited the survival of human gastric (AGS) and brea (MCF-7) adenocarcinoma cells. Also, GTS inhibited the TRPM7-like currents in AGS and MCF-7 cells. The GTS-mediated cytotoxicity was inhibited by TRPM7-specific siRNA. In addition, we showed that overexpression of TRPM7 channels in HEK293 cells was inhibited by GTS. Thus, TRPM7 channels are involved in GTS-mediated cell death in AGS and MCF-7 cells, and these channels may represent a novel target for physiological disorders where GTS plays an important role.

Involvement of melastatin type transient receptor potential 7 channels in ginsenoside Rd-induced apoptosis in gastric and breast cancer cells

  • Kim, Byung Joo
    • Journal of Ginseng Research
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    • 제37권2호
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    • pp.201-209
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    • 2013
  • Ginsenoside, one of the active ingredients of Panax ginseng, has a variety of physiologic and pharmacologic effects. The purpose of this study was to explore the effects of ginsenoside Rd (G-Rd) on melastatin type transient receptor potential 7 (TRPM7) channels with respect to the proliferation and survival of AGS and MCF-7 cells (a gastric and a breast cancer cell line, respectively). AGS and MCF-7 cells were treated with different concentrations of G-Rd, and caspase-3 activities, mitochondrial depolarizations, and sub-G1 fractions were analyzed to determine if cell death occurred by apoptosis. In addition, human embryonic kidney (HEK) 293 cells overexpressing TRPM7 channels were used to confirm the role of TRPM7 channels. G-Rd inhibited the proliferation and survival of AGS and MCF-7 cells and enhanced caspase-3 activity, mitochondrial depolarization, and sub-G1 populations. In addition, G-Rd inhibited TRPM7-like currents in AGS and MCF-7 cells and in TRPM7 channel overexpressing HEK 293 cells, as determined by whole cell voltage-clamp recordings. Furthermore, TRPM7 overexpression in HEK 293 cells promoted G-Rd induced cell death. These findings suggest that G-Rd inhibits the proliferation and survival of gastric and breast cancer cells by inhibiting TRPM7 channel activity.

The serine threonine kinase RIP3: lost and found

  • Morgan, Michael J.;Kim, You-Sun
    • BMB Reports
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    • 제48권6호
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    • pp.303-312
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    • 2015
  • Receptor-interacting protein kinase-3 (RIP3, or RIPK3) is an essential protein in the "programmed", or "regulated" necrosis cell death pathway that is activated in response to death receptor ligands and other types of cellular stress. Programmed necrotic cell death is distinguished from its apoptotic counterpart in that it is not characterized by the activation of caspases; unlike apoptosis, programmed necrosis results in plasma membrane rupture, thus spilling the contents of the cell and triggering the activation of the immune system and inflammation. Here we discuss findings, including our own recent data, which show that RIP3 protein expression is absent in many cancer cell lines. The recent data suggests that the lack of RIP3 expression in a majority of these deficient cell lines is due to methylation-dependent silencing, which limits the responses of these cells to pro-necrotic stimuli. Importantly, RIP3 expression may be restored in many cancer cells through the use of hypomethylating agents, such as decitabine. The potential implications of loss of RIP3 expression in cancer are explored, along with possible consequences for chemotherapeutic response. [BMB Reports 2015; 48(6): 303-312]

Effect of Ethanol on Mouse Brain Cell

  • Jang, Hyung Seok
    • 대한임상검사과학회지
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    • 제47권1호
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    • pp.51-58
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    • 2015
  • Ethanol has long been implicated in triggering apoptotic neurodegeneration. Alcohol also may indirectly harm the fetus by imparing the mother's physiology. We examined the effects of ethanol on immature brain of mice. Three-weeks-old female ICR strain mice daily intraperitoneally injected with ethanol at the concentration of 4 and 20% in saline for 0, 6, and 24 hours and 1 and 4 weeks. The mice were weighted and sacrificed, and the brains were ectomized for the present histological, immunohistochemical and TUNEL assays. Based on the histologic hematoxylin and eosin stain, immunohistochemical expression of glutamate receptor protein and neuronal cell adhesion molecule (NCAM) were evaluated. The cerebral cortex of the ethanol-treated group showed few typical symptoms of apoptosis such as chromosome condensation and disintegration of the cell bodies. TUNEL staining revealed DNA fragmentation in the 6 and 24 hours. This results demonstrated that acute ethanol administration causes neuronal cell death. I found that either glutamate receptor inhibition or activation could induce cerebellar degeneration as ethanol effect. Neuronal death also can be induced by excess activity of certain neurotransmitter, including glutamate. Neurons must establish cell-to-cell contact during growth and development in order to survive, migrate to their final destination, and develop appropriate connections with neighboring cell. Purkinje cell in cerebellar are especially vulnerable to the cell death and degeneration. After ethanol treatment in cerebellar, NCAM had decreased by 4 weeks. This result suggest that apoptosis seems to be involved in the slow elimination of neuron and cerebellar degeneration.

Protopanaxadiol ameliorates palmitate-induced lipotoxicity and pancreatic β-cell dysfunction in INS-1 cells

  • Dahae Lee;Sungyoul Choi;Ki Sung Kang
    • Journal of Ginseng Research
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    • 제47권4호
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    • pp.572-582
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    • 2023
  • Background: Free fatty acid-induced lipotoxicity is considered to play an important role in pancreatic β-cell dysfunction. The effect of ginsenosides on palmitic acid-induced pancreatic beta-cells cell death and failure of glucose-stimulated secretion of insulin (GSIS) was evaluated in this study. Methods: Enzyme-linked immunosorbent assay kit for a rat insulin was used to quantify glucose-stimulated insulin secretion. Protein expression was examined by western blotting analysis. Nuclear condensation was measured by staining with Hoechst 33342 stain. Apoptotic cell death was assessed by staining with Annexin V. Oil Red O staining was used to measure lipid accumulation. Results: We screened ginsenosides to prevent palmitic acid-induced cell death and impairment of GSIS in INS-1 pancreatic β-cells and identified protopanaxadiol (PPD) as a potential therapeutic agent. The protection effect of PPD was likely due to a reduction in apoptosis and lipid accumulation. PPD attenuated the palmitic acid-induced increase in the levels of B-cell lymphoma-2-associated X/B-cell lymphoma 2, poly (ADP-ribose) polymerase and cleaved caspase-3. Moreover, PPD prevented palmitic acid-induced impairment of insulin secretion, which was accompanied by an increase in the activation of phosphatidylinositol 3-kinase, peroxisome proliferator-activated receptor γ, insulin receptor substrate-2, serine-threonine kinase, and pancreatic and duodenal homeobox-1. Conclusion: Our results suggest that the protective effect of PPD on lipotoxicity and lipid accumulation induced by palmitic acid in pancreatic β-cells.

A549 인체폐암세포에서 상백피 메틸렌클로라이드 추출물에 의한 Apoptosis 및 Autophagy 유발 (Apoptosis and Autophagy Induction of A549 Human Lung Cancer Cells by Methylene Chloride Extracts of Morus alba L.)

  • 박신형;지규용;최영현;엄현섭
    • 동의생리병리학회지
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    • 제24권6호
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    • pp.942-949
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    • 2010
  • Morus alba L., a kind of Oriental medicinal herbs, has been traditionally used to treat pulmonary asthma and congestion. According to recent studies, extracts of M. alba L. have showed anti-inflammatory, anti-oxidant, anti-tumor and hypoglycemic effects. However, the molecular mechanisms on how it acts as a death-inducer in cancer cells have not been fully understood. In this study, we investigated the cell death effects of methylene chloride extracts of M. alba L. (MEMA) in A549 human lung carcinoma cells. It was shown that MEMA induced the apoptotic cell death proved by increased sub-G1 phase cell population, apoptotic body formation and chromatin condensation. MEMA treatment induced the expression of death receptor-related proteins such as death receptor (DR) 4, DR5, Fas and FasL, which further triggered the activation of caspase-8 and the cleavage of Bid in a concentration-dependent manner. However, MEMA reduced anti-apoptotic Bcl-2 and Bcl-xL expression which contributed to the loss of mitochondrial membrane potential (MMP), and the activations of caspase-9 and caspase-3. Meanwhile, the morphological study indicated a characteristic finding of autophagy, such as the formation of autophagosomes in MEMA-treated cells. Furthermore, markers of autophagy, namely, the increased MDC-positive cells, conversion of microtubule-associated protein light chain 3 (LC3)-I to LC3-II and increased beclin-1 accumulation, were observed. Taken together, these findings demonstrated that MEMA triggered both autophagy and apoptosis in A549 cancer cells. They might suggest that M. alba L. could be a prospective clinical application to treat human lung cancers.

FADD 과발현 평활근세포에서 분비하는 Turner Necrosis Factor-α의 작용 (Biological Activity of Tumor Necrosis Factor-α Secreted from Smooth Muscle Cell Overexpressing FADD)

  • 김선미;이경아;김관회
    • 생명과학회지
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    • 제17권1호
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    • pp.45-50
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    • 2007
  • 세포 배양액에 tetracycline이 없는 경우 FADD를 발현하면서 사멸하는 평활근세포 (FADD-SMC)에서 분비하는 $TNF-\alpha$의 활성을 조사하였다. 배양액에 tetracycline이 없는 경우 FADD-SMC는 약 1000 pg/ml의 $TNF-\alpha$를 분비하였다. $TNF-\alpha$를 포함하는 배양액을 분리하고, 이 배양액을 정상세포에 처리한 결과 인산화한 p38 MAPK와 nuclear, factor, kappa B (NF-kB)의 활성이 증가하였다. 또한 이 배양액을 L929 세포에 처리하는 경우 세포독성이 발생하였다. NF-kB, p38 MAPK 그리고 L929 세포에 대찬 효과는 배양액에서 suluble TNF receptor를 이용하여 $TNF-\alpha$를 제거하는 경우 감소하였다.

성장호르몬수용체 유전자를 지닌 형질전환생쥐의 세대전달율 및 치사율 (Transmission and Death Rates in Transgenic Mice Containing Growth Hormone Receptor Gene)

  • Kim, H.J.;Jin, D.I.
    • 한국가축번식학회지
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    • 제25권1호
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    • pp.85-90
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    • 2001
  • 본 연구는 growth hormone receptor(GHR) gene의 동물생리에 미치는 영향을 연구하기 위해 metallothionein promoter와 GHR gene을 이용하여 생쥐의 1-cell 수정란에 DNA 미세주입법에 의해 형질전환생쥐를 생산하였다. 세마리의 형질전환생쥐가 생산되었는데 DNA 분석결과 4~8 copy의 GHR 유전자를 지닌 것으로 확인되었다 이들 세 마리의 GHR 형질전환생쥐를 정상 형질전환생쥐와 교미시켜 F$_1$과 F$_2$ 새끼를 생산하였는데 이들의 전달율은 F$_1$에서 20~50%였고 F$_2$에서는 약 50%를 나타내어 모자익형태로 유전자가 정착되었음을 확인할 수 있었다. 3주령까지의 사망률은 Fl과 F2 새끼에서 약 10~30%를 나타내어 GHR유전자의 발현이형질전환생쥐의 초기 사망에 영향을 미치는 것으로 나타났다.

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