• Asian Pacific Journal of Cancer Prevention
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• 제15권10호
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• pp.4353-4358
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• 2014

Background: PI3/AKT and NF-kB signaling pathways are constitutively active in acute myeloid leukemia and cross-talk between the two has been shown in various cancers. However, their role in acute myeloid leukemia has not been completely explored. We therefore used cell penetrating inhibitor peptides to define the contributions of AKT and NF-kB to survival and multi drug resistance (MDR) in HL-60 cells. Materials and Methods: Inhibition of AKT and NF-kB activity by AKT inhibitor peptide and NBD inhibitor peptide, respectively, resulted in decreased expression of mRNA for the MDR1 gene as assessed by real time PCR. In addition, treatment of HL-60 cells with AKT and NBD inhibitor peptides led to inhibition of cell viability and induction of apoptosis in a dose dependent manner as detected by flow cytometer. Results: Finally, co-treatment of HL-60 cells with sub-optimal doses of AKT and NBD inhibitor peptides led to synergistic apoptotic responses in AML cells. Conclusions: These data support a strong biological link between NF-kB and PI3-kinase/AKT pathways in the modulation of antiapoptotic and multi drug resistant effects in AML cells. Synergistic targeting of these pathways using NF-kB and PI3-kinase/AK inhibitor peptides may have a therapeutic potential for AML and possibly other malignancies with constitutive activation of these pathways.

• BMB Reports
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• 제41권12호
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• pp.840-845
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• 2008

Nucleophosmin/B23, a major nucleolar phosphoprotein, is overexpressed in actively proliferating cells. In this study, we demonstrate that B23 exclusively localizes in the nucleolus, whereas ATP depletion results in the redistribution of B23 throughout the whole nucleus and destabilizes B23 via caspase-3 mediated cleavage. Interestingly, ATP binding precedes PI(3,4,5)P3 binding at lysine 263 and ATP binding mutants fail to restore the anti-apoptotic functions of B23 in PC12 cells. Thus, the ATP-B23 interaction is required for the stability of the B23 protein and regulates cell survival, confining B23 within the nucleolus in PC12 cells.

• 생명과학회지
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• 제19권8호
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• pp.1073-1080
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• 2009

비스테로이드성 항염증약(nonsteroidal anti-inflammatory drugs; NSAIDs)은 항염 및 진통효과를 나타내며, 염증억제 외에 다양한 신호전달 분자를 통해 여러 가지 세포생리활성을 조절하며, 암세포에서는 세포사멸 유도를 통한 항암제 효과를 보이고 있다. 본 연구에서는 NSAIDs가 암세포사멸프로그램을 작동시키는데 있어 phosphatidyl inositol 3-kinase (PI3K)-Akt/protein kinase B (PKB) 그리고 MEK1/2-ERK1/2 신호 전달계과 같은 anti-apoptotic program이 NSAIDs의 효과를 경감시키는 것으로 예상하고, 이들 항세포사멸 프로그램을 억제하였을 경우, NSAIDs의 세포사멸 유도작용이 증가되는지 그 가능성을 조사하였다. 세포사멸은 Hoeschst 33342으로 핵응축과 핵 쪼개짐을 염색하여 확인하였다. Western blotting을 통해 단백질 발현과 역전사중합효소연쇄반응을 통해 mRNA 발현을 확인하였다. NSAIDs 처리와 동시에 PI3K-Akt/PKB와 MEK-ERK1/2 신호전달계의 억제제를 함께 처리했을 때, NSAIDs의 세포사멸유도작용이 증가함을 확인하였다. 또한 PI3K와 MEKl/2 신호전달계의 상위에 존재하는 receptor tyrosine kinases (RTKs)의 억제제인 genistein을 함께 처리하였을 때에도 유사한 효과가 나타남을 확인하였다. 그리고 이들 복합처리에 의해 NAG-1 발현이 증가하며 NAG-1 interference 하였을 경우 복합처리에 의한 세포사멸증진 효과가 사라짐을 확인하였다. 본 연구결과는 암세포에 활성화 되어 있는 세포생존프로그램을 제어하는 물질(genistein 혹은 LY294002+U0126)을 복합처방함으로써 NSAIDs의 항암작용을 증진시킬 수 있음을 보여준다.

• Biomolecules & Therapeutics
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• 제24권3호
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• pp.268-282
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• 2016

In the present study, we investigated the anti-inflammatory properties of Eucommia ulmoides Oliv. Bark. (EUE) in lipopolysaccharide (LPS)-stimulated microglial BV-2 cells and found that EUE inhibited LPS-mediated up-regulation of pro-inflammatory response factors. In addition, EUE inhibited the elevated production of pro-inflammatory cytokines, mediators, and reactive oxygen species (ROS) in LPS-stimulated BV-2 microglial cells. Subsequent mechanistic studies revealed that EUE suppressed LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs), phosphoinositide-3-kinase (PI3K)/Akt, glycogen synthase $kinase-3{\beta}$ ($GSK-3{\beta}$), and their downstream transcription factor, nuclear factor-kappa B ($NF-{\kappa}B$). EUE also blocked the nuclear translocation of $NF-{\kappa}B$ and inhibited its binding to DNA. We next demonstrated that EUE induced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulated heme oxygenase-1 (HO-1) expression. We determined that the significant up-regulation of HO-1 expression by EUE was a consequence of Nrf2 nuclear translocation; furthermore, EUE increased the DNA binding of Nrf2. In contrast, zinc protoporphyrin (ZnPP), a specific HO-1 inhibitor, blocked the ability of EUE to inhibit NO and $PGE_2$ production, indicating the vital role of HO-1. Overall, our results indicate that EUE inhibits pro-inflammatory responses by modulating MAPKs, PI3K/Akt, and $GSK-3{\beta}$, consequently suppressing $NF-{\kappa}B$ activation and inducing Nrf2-dependent HO-1 activation.

• Parasites, Hosts and Diseases
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• 제54권3호
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• pp.247-252
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• 2016

This study was conducted to investigate the occurrence of oxidative stress in the heart tissue of rats infected with Trypanosoma evansi. Rats were divided into 2 groups (A and B) with 12 animals each, and further subdivided into 4 subgroups (A1 and A2, 6 animals/each; and B1 and B2, 6 animals/each). Animals in the groups B1 and B2 were subcutaneously inoculated with T. evansi. Thiobarbituric acid reactive substances (TBARS), superoxide dismutase activity (SOD), glutathione S-transferase activity (GST), reduced glutathione activity (GSH), and non-protein thiols (NPSH) in the heart tissue were evaluated. At day 5 and 15 post-infection (PI), an increase in the TBARS levels and a decrease in the SOD activity (P<0.05) were observed. GSH and GST activities were decreased in infected animals at day 15 PI (P<0.05). Considering the proper functioning of the heart, it is possible that the changes in the activity of these enzymes involved in the oxidative stress may be related, at least in part, in the pathophysiology of rats infected with T. evansi.

• Molecules and Cells
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• 제28권1호
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• pp.13-17
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• 2009

Basic fibroblast growth factor (bFGF) plays an important role in angiogenesis. However, the underlying mechanisms are not clear. $Mg^{2+}$ is the most abundant intracellular divalent cation in the body and plays critical roles in many cell functions. We investigated the effect of bFGF on the intracellular $Mg^{2+}$ concentration ($[Mg^{2+}]_i$) in human umbilical vein endothelial cells (HUVECs). bFGF increased ($[Mg^{2+}]_i$) in a dose-dependent manner, independent of extracellular $Mg^{2+}$. This bFGF-induced $[Mg^{2+}]_i$ increase was blocked by tyrosine kinase inhibitors (tyrphostin A-23 and genistein), phosphatidylinositol 3-kinase (PI3K) inhibitors (wortmannin and LY294002) and a phospholipase $C{\gamma}$ ($PLC{\gamma}$) inhibitor (U73122). In contrast, mitogen-activated protein kinase inhibitors (SB202190 and PD98059) did not affect the bFGF-induced $[Mg^{2+}]_i$ increase. These results suggest that bFGF increases the $[Mg^{2+}]_i$ from the intracellular $Mg^{2+}$ stores through the tyrosine kinase/PI3K/$PLC{\gamma}$-dependent signaling pathways.

• Journal of Plant Biology
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• 제35권1호
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• pp.25-36
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• 1992

Chlorella 엽록체에서 인지질 생합성과 그의 지방산 조성에 미치는 amphotericin B($150\;\mu\textrm{g}/ml$)와 cycloheximide($10\;\mu\textrm{g}/ml$)의 영향을 분석하였다. Total lipid와 인지질 함량(PC, PE, PI)은 항생제 처리구가 대조구에 비하여 낮았다. Whole cell system에서의 주요 지방산은 대조구에서는 palmitic acid(31.96%)와 linoleic acid(16.96%)로 나타났으나 amphotericin B 처리구에서는 palmitic acid(36.15%)와 linolenic acid(16.71%)로 분석되었다. 또한 cycloheximide 처리구에서는 palmitic acid(31.90%)와 stearic acid(15.32%)가 인지질 형성에 이용되었다. 분리한 엽록체의 대조구(33.75%, 18.90)와 amphotericin B 처리(36.75%, 9.46%)에서 분리한 엽록체에서 인지질 형성에 이용되는 주요 지방산은 palmitic acid와 linolenic aicd였으나 cycloheximide 처리구에서는 palmitic acid(28.01%)와 oleic acid(19.27%)가 인지질생합성에 도입된 것으로 분석되었다.

• 한국전자파학회논문지
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• 제13권2호
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• pp.123-129
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• 2002

5-bit 광대역 MMIC(Monolithic Microwave Integrated Circuit) 위상 변위기를 설계 및 제작하였다. 광대역 동작 특성을 위해서 11.25$^{\circ}$, 22.5$^{\circ}$, 45$^{\circ}$, 90$^{\circ}$ bit는 Lange 커플러를 이용한 reflection 형태로 설계되었으며, 180 $^{\circ}$bit 는 Lange 커플러를 사용한 shorted coupled line과 전송선을 $\pi$-network 형태로 만든 구조를 이용하여 구현되었고, Lange 커플러로 인한 전체 회로의 크기가 커지는 것을 막기 위해서 커플러를 크게 구부려 회고의 크기를 작게 하였다. 또한 손실이 작은 PIN 다이오드를 사용하여 각 bit에서 스위치로 사용하였다. 제작된 5-bit 광대역 위상 변위기는 5개의 주요 위상에 대하여 RMS 위상 오차 3.5$^{\circ}$, 최대 삽입손실 12.5 dB, 최대 입.출력 반사 손실 7 dB와 10 dB의 측정결과를 되였다. 제작된 위상 변위기 회로의 크기는 6.5$\times$5.3 $ extrm{mm}^2$ 이다.

• International Journal of Industrial Entomology and Biomaterials
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• 제23권1호
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• pp.107-113
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• 2011

Infection effect of $Nosema$ $bombyics$ on the midgut of silkworm $Bombyx$ $mori$ and subsequent appearance of spores and the performance of larvae was studied. Autopsy of larvae showed white pustules on the surface of midgut at 5 days of post infection (pi). At later stage, important organs like midgut, silk gland and gonads reduced in size and all these organs showed white pustules. Light microscope observation of pustules revealed enormous spores. Spore multiplication was at a faster rate in young larvae. Infection of the adult larvae resulted in pebrinized pupa and moths. Larval weight, cocoon weight and cocoon shell ratio reduced as the post infection period increased. Transverse sections of midgut showed $N.$ $bombycis$ infection limited to a few columnar cells at 3-5 days of pi. At 7 days pi, cell volume increased, cells were swollen and elongated. Heavily infected cells looked like sacks filled with parasite and the apical region of certain cells were bulging into the gut lumen. Later at 8-9 days of pi, spores or its developing stages leaked into the lumen either freely or enclosed within the globules of host cytoplasm. Besides columnar cells, development of $N.$ $bombycis$ was observed in the regenerative cells and rarely in goblet cells. Development of $N.$ $bombycis$ was also observed in both longitudinal and circular muscles at the late pi period. The histopathological changes, deformities and spore production time in the host were all influenced by the spore dosage and age of the host.

• 생명과학회지
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• 제31권8호
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• pp.729-735
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• 2021

제 2 형 당뇨병은 조직의 포도당 흡수 능력에 이상이 있을 때 발생하며, 인슐린에 의한 포도당 섭취와 신진대사는 혈당을 유지하는 기본 활동이며 포도당 섭취는 인슐린이 세포 표면의 수용체에 결합하여 시작되는 다양한 신호 단계를 거친다. 본 연구는 Ecklonia cava에서 분리된 활성 화합물 인 2,7-phloroglucinol-6,6-bieckol이 3T3-L1 지방 세포에서 인슐린 신호전달체계에 따른 포도당 흡수 증가에 미치는 영향에 대한 것이다. 2,7-phloroglucinol-6,6-bieckol 은 3T3-L1 지방 세포에서 농도의존적으로 GLUT4의 발현을 증가시켜 원형질막에서의 glucose uptake 를 증가시켰다. 이는 인슐린 신호 전달 경로에서 2,7-phloroglucinol-6,6-bieckol 에 의한 IRS-1, AKT의 인산화 및 PI3K 활성화에 의한 것이다. PHB는 또한 AMPK 인산화와 활성화를 자극했다. 2,7-phloroglucinol-6,6-bieckol에 의한 PI3K/AKT 및 AMPK 경로의 인산화 및 활성화는 wortmannin (PI3K 억제제) 및 화합물 C (AMPK 억제제)를 사용하여 확인하였다. 본 연구에서 2,7-phloroglucinol-6,6-bieckol 이 3T3-L1 지방 세포에서 PI3K 및 AMPK 경로를 통해 원형질막으로의 GLUT4 전위를 촉진함으로써 포도당 흡수를 증가시킬 수 있음을 나타내었다. 이러한 결과는 2,7-phloroglucinol-6,6-bieckol 가 인슐린 감수성을 개선하는 데 도움이 될 수 있음을 시사한다.