• 제목/요약/키워드: PD-L2

검색결과 283건 처리시간 0.022초

FGF-2 inhibits TNF-α mediated apoptosis through up-regulation of Bcl2-A1 and Bcl-xL in ATDC5 cells

  • Kim, Hey-Ryun;Heo, Youn-Moo;Jeong, Kyoung-Il;Kim, Yong-Min;Jang, Hae-Lan;Lee, Kwang-Yeol;Yeo, Chang-Yeol;Kim, Sung-Hoon;Lee, Hak-Kyo;Kim, Seung-Ryul;Kim, Eung-Gook;Choi, Joong-Kook
    • BMB Reports
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    • 제45권5호
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    • pp.287-292
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    • 2012
  • FGF-2 is involved in cell survival, proliferation, apoptosis, and angiogenesis in a wide variety of cells. FRGRs, PI3K and MAP kinases are well known mediators of FGF signaling. Despite its known roles during many developmental processes, including osteogenesis, there are few known targets of FGF-2. In the present study, we identified Bcl2-A1 and Bcl-xL as two prominent targets involved in promoting cell survival. Pretreatment of ATDC5 cells with FGF-2 increased cell survival, while siRNAs specific for Bcl2-A1 and Bcl-xL compromised the anti-apoptotic effect of FGF-2, sensitized the cells to apoptosis triggered by TNF-${\alpha}$. Chemical inhibition of FGFR, NFkB, and PI3K activity by PD173074, pyrrolidine dithiocarbamate, and LY294002 respectively abrogated the FGF-2-mediated induction of Bcl2-A1 and Bcl-xL expression. Taken together, our data demonstrate that a subset of Bcl2 family proteins are the targets of FGF-2 signaling that promotes the survival of ATDC5 cells.

L6 근육세포에서 포도당 수송능에 미치는 $CdCl_2$의 영향 (Effects of Cadmium on Glucose Transport in L6 Myocytes)

  • 강동희;길이룡;박광식;이병훈;문창규
    • Environmental Analysis Health and Toxicology
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    • 제20권1호
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    • pp.75-85
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    • 2005
  • This study was aimed to know the effect of cadmium chloride (CdCl₂) on glucose transport in L6 myotube and its action mechanism. CdCl₂ increased the 2-deoxy- (l-3H)-D-glucose (2-DOG) uptake 1.9 and 2.4 fold at 10 and 25 μM respectively. To investigate the stimulating-mechanism of glucose transport induced by CdCl₂, the wortmannin and PD98059 were used as PI3K (phosphatidylinositol 3-kinase) inhibitor and MAPK inhibitor respectively, which did not affect 2-DOG uptake. This fact suggests that CdCl₂ induced 2-DOG uptake may not be concerned to the insulin signalling pathway. Whereas nifedipine, a calcium channel blocker, and trifluoperazine, a calmodulin inhibitor, were found to inhibit the 2-DOG uptake stimulted by CdCl₂. In addition, we also measured the ROS (reactive oxygen species) production and GSH level in L6 myotube to investigate the correlation between the glucose uptake and ROS. CdCl₂(25 μM) increased ROS generation approximately 1.5 fold and changed the cellular GSH level, but GSSG/GSH ratio remained unchanged. CdCl₂ stimulated 2-DOG uptake and ROS generation were inhibited by N-acetylcystein. And BSO pretreatment, a potent inhibitor of γ-GCS, resulted in the dramatic decrease of 2-DOG uptake and also the increase of the sensitivity to cadmium cytotoxicity. The obtained results suggest that CdCl₂-stimulated glucose uptake might be based on the activation of HMP shunt as an antioxidant defense mechanism of the cells.

Nrf2 in TIME: The Emerging Role of Nuclear Factor Erythroid 2-Related Factor 2 in the Tumor Immune Microenvironment

  • Jialin Feng;Oliver J. Read;Albena T. Dinkova-Kostova
    • Molecules and Cells
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    • 제46권3호
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    • pp.142-152
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    • 2023
  • Nuclear factor erythroid 2-related factor 2 (Nrf2) mediates the cellular antioxidant response, allowing adaptation and survival under conditions of oxidative, electrophilic and inflammatory stress, and has a role in metabolism, inflammation and immunity. Activation of Nrf2 provides broad and long-lasting cytoprotection, and is often hijacked by cancer cells, allowing their survival under unfavorable conditions. Moreover, Nrf2 activation in established human tumors is associated with resistance to chemo-, radio-, and immunotherapies. In addition to cancer cells, Nrf2 activation can also occur in tumor-associated macrophages (TAMs) and facilitate an anti-inflammatory, immunosuppressive tumor immune microenvironment (TIME). Several cancer cell-derived metabolites, such as itaconate, L-kynurenine, lactic acid and hyaluronic acid, play an important role in modulating the TIME and tumor-TAMs crosstalk, and have been shown to activate Nrf2. The effects of Nrf2 in TIME are context-depended, and involve multiple mechanisms, including suppression of proinflammatory cytokines, increased expression of programmed cell death ligand 1 (PD-L1), macrophage colony-stimulating factor (M-CSF) and kynureninase, accelerated catabolism of cytotoxic labile heme, and facilitating the metabolic adaptation of TAMs. This understanding presents both challenges and opportunities for strategic targeting of Nrf2 in cancer.

Swellable Submicrospheres of Ionic Palladium(II) Complexes Containing Decylmethylbis(m-pyridyl)silane

  • Ryu, Yoon-Kyong;Kim, Cho-Rong;Kim, Chi-Won;Noh, Tae-Hwan;Jung, Ok-Sang
    • Bulletin of the Korean Chemical Society
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    • 제30권10호
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    • pp.2338-2340
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    • 2009
  • Ionic palladium(II) complex containing a long aliphatic chain, [(tmeda)$PdL]_2(PF_6)_4$ (tmeda = N,N,N',N'-tetramethylethylenediamine; L = decylmethylbis(m-pyridyl)silane) allowed to form a puckered submicrosphere morphology without any template or additive. The puckered spheres reversibly adsorb and desorb dioxane molecules. Coligand and cosolvent effects on the formation of submicrospherical morphology were observed.

Synthesis, Structures, and Catalytic Properties of Ionic Metallacyclodimeric Palladium(II) Complexes

  • Kim, Sung Min;Park, Kyung Hwan;Lee, Haeri;Moon, So Yun;Jung, Ok-Sang
    • Bulletin of the Korean Chemical Society
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    • 제33권12호
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    • pp.4069-4073
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    • 2012
  • Metallacyclodimeric complexes of $[(Me_4en)Pd(L)]_2(ClO_4)_4$ ($Me_4en$ = N,N,N',N'-tetramethylethylenediamine; L = dimethylbis(4-pyridyl)silane (dmps), methylvinylbis(4-pyridyl)silane (mvps)) have been synthesized, and their structures have been characterized by X-ray single crystallography. The skeletal structures consist of one 20-membered metallamacrocycle, two 5-membered metallacycles, and four pyridyl groups. The local geometry around the palladium(II) ion approximates to a typical square planar arrangement with four nitrogen donors. Delicate difference in catalytic effects on hydrogenation was investigated based on the structure of catalyst and substrates.

Hitting the complexity of the TIGIT-CD96-CD112R-CD226 axis for next-generation cancer immunotherapy

  • Jin, Hyung-seung;Park, Yoon
    • BMB Reports
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    • 제54권1호
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    • pp.2-11
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    • 2021
  • Antibody-based therapeutics targeting the inhibitory receptors PD-1, PD-L1, or CTLA-4 have shown remarkable clinical progress on several cancers. However, most patients do not benefit from these therapies. Thus, many efforts are being made to identify new immune checkpoint receptor-ligand pathways that are alternative targets for cancer immunotherapies. Nectin and nectin-like molecules are widely expressed on several types of tumor cells and play regulatory roles in T- and NK-cell functions. TIGIT, CD226, CD96 and CD112R on lymphoid cells are a group of immunoglobulin superfamily receptors that interact with Nectin and nectin-like molecules with different affinities. These receptors transmit activating or inhibitory signals upon binding their cognate ligands to the immune cells. The integrated signals formed by their complex interactions contribute to regulating immune-cell functions. Several clinical trials are currently evaluating the efficacy of anti-TIGIT and anti-CD112R blockades for treating patients with solid tumors. However, many questions still need to be answered in order to fully understand the dynamics and functions of these receptor networks. This review addresses the rationale behind targeting TIGIT, CD226, CD96, and CD112R to regulate T- and NK-cell functions and discusses their potential application in cancer immunotherapy.

Pseudodeficiency 및 potential late onset Pompe disease 보인자로 확인된 cis형 dual variant 돌연변이 두 개를 가진 여아 1례 (A Case of Pseudodeficiency in a Potential Late Onset Pompe Disease Carrier, with Double Dual Variant, Each in cis Formation)

  • 김승호;김구련;장영표;이동환
    • 대한유전성대사질환학회지
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    • 제22권2호
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    • pp.58-62
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    • 2022
  • 폼페병(PD, Pompe disease), 2형 당원축적병(Glycogen storage disease type II)은 보통염색체 열성 질환으로 용해소체 효소인 acid maltase (acid α-glucosidase, GAA) 결핍으로 인한 대사근육병이다. 한 종류의 효소 결핍에 의한 질환이지만, GAA의 결핍정도와 유전자형에 따라 임상양상이 다르게 나타난다. 발병 시기에 따라 크게 영아형 폼페병(infantile onset Pompe disease, IOPD), 성인형 폼페병(late onset Pompe disease, LOPD)으로 나눌 수 있다. 저자들은 신생아기 때 호흡곤란증후군을 진단받고 치료받은 후 잠시 혈중 CK 증가가 확인되었으나 다른 임상증상 없이 경과 관찰 후 호전되었고, LSD 스크리닝 검사 결과 상 GAA 수치가 0.58 umol/h/L로 감소되어 있음을 확인한 1례에 대해 보고하고자 한다. 해당 환아를 PD 의증으로 고려하여 시행한 GAA enzyme essay 상 total GAA level은 16.2 nmol/2hr/mg protein, GAA with acarbose level은 2.0 nmol/2hr/mg protein, acarbose/total level의 비율은 12.0%로 낮은 수치를 확인하였다. 환아의 유전자 검사 상 exon #4에서 두개의 likely pathogenic heterozygous mutation인 c.752C>T (p.Ser251Leu), c.761C>T (p.Ser254Leu), exon #12에서 heterozygous mutation인 c.1726G>A (p.Gly576Ser), exon #15에서 heterozygous mutation인 c.2065G>A (p.Glu689 Lys)이 확인되었다. 환아의 7세 오빠는 유전자 검사에서 정상으로 확인되었고, 아버지는 환아에서 동일하게 확인된 exon #12에서 heterozygous mutation인 c.1726G>A(p.Gly576Ser), exon #15에서 heterozygous mutation인 c.2065G>A (p.Glu689Lys)이, 어머니에서는 exon #4에서 두 개의 likely pathogenic heterozygous mutation인 c.752C>T (p.Ser251Leu), c.761C>T (p.Ser254Leu)가 확인되었다. Pathogenic한 유전자 두개가 있으면 보통 환자로 인식될 수 있으나 이 환아에서처럼 pathogenic한 유전자 두 개가 있더라도 cis 형태로 하나처럼 움직인 경우 PD 환자가 아니라 carrier 일 수 있다는 것을 경험한 증례였다. 이에 PD 환아의 유전검사 결과를 해석할 시 pathogenic variant 유전자가 두 개일지라도 혹시 cis 형태로 하나의 유전자인지를 확인하여, pseudodeficiency나 potential LOPD carrier일 수 있는 점을 고려하며 여러 임상 양상을 취합하여 진료를 시행하는 것이 필요하다.

배양림프구에서 Paraquat의 세포독성에 대한 Vitamin C와 Deferoxamine의 항산화 효과 (The Antioxidant Effect of Vitamin C and Deferoxamine on Paraquat-induced Cytotoxicity in Cultured Lymphocytes)

  • 어은경;김경희
    • 대한임상독성학회지
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    • 제4권1호
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    • pp.7-16
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    • 2006
  • Purpose: As basic information of antioxidant treatments for the patient with paraquat intoxication, in human peripheral lymphocytes, the cytotoxicity of paraquat was measured, and to evaluate the antioxidant effect of vitamin C and deferoxamine against this cytotoxicity, malondialdehyde (MDA), superoxide dismutase (SOD) activity and total antioxidant status (TAS) were measured. Methods: From 10 healthy adults, after obtaining a consent, 20ml peripheral blood was collected. Experimental groups were divided to (1) control group, the group treated with an identical amount of saline, (2) P group: the group treated with paraquat only, (3) PV group: the group treated with paraquat followed by vitamin C 30 minutes later, (4) PD group: the group treated with paraquat followed by deferoxamine 30 minutes later, (5) PVD group: the group treated with paraquat followed by vitamin C 30 minutes later and subsequently deferoxamine one hour later, and (6) PDV group: the group treated with paraquat followed by deferoxamine 30 minutes later and subsequently vitamin C 1 hour later, and thus to total 6 groups. In each group, 10 samples of peripheral blood was assigned and $100{\mu}M\;paraquat,\;100{\mu}M$ vitamin C, and $100{\mu}M$ deferoxamine were used as reagent. Lymphocytes were isolated, cultured, and cytotoxicity was measured by the Microculture Tetrazolium method (MTT assay), MDA and SOD activity, and TAS concentration were measured. Results: In regard to the cytotoxicity measured in each group, their cytotoxicity was decreased in the group treated with antioxidants, in comparison with the group treated with paraquat only. In the cases that the order of the treatment of these two antioxidants was altered, viability in the PDV group $(1.077{\pm}0.121)$ was increased more that the PVD group $(0.888{\pm}0.152)$ statistically significantly (p=0.018). Concerning the amount of MDA, in comparison with the P group $(6.78{\pm}0.93{\mu}mol/L)$, after the treatment of each antioxidant, the concentration of MDA was decreased statistically significantly (p<0.05). In the group treated with two antioxidants together, in comparison with the group treated only with one antioxidant, the amount of MDA was increased statistically significantly $(PV:\;3.96{\pm}0.98{\mu}mol/L,\;PD:\;4.92{\pm}1.50{\mu}mol/L,\;PVD:\;3.22{\pm}0.83{\mu}mol/L,\;and\;PDV:\;3.42{\pm}0.95{\mu}mol/L,\;p=0.007)$. The concentration of SOD measured in the blood in each group after the administration of paraquat, in comparison with the control group, a pattern of the elevation of SOD activity and subsequent decrease was detected, however, it was not statistically significant. In the comparison of the groups treated with antioxidants, in comparison with the P group $(1419.9{\pm}265.9{\mu}mol/L)$, SOD activity was decreased statistically significantly in only the PDV group $(1176.4{\pm}238.9{\mu}mol/L)$ (p=0.017). In regard to TAS measured in each group, in comparison with the P group $(0.87{\pm}0.05{\mu}mol/L)$, in all groups treated with the antioxidants, the PV group was $1.00{\pm}0.03{\mu}mol/L$ (p=0.005), the PD group was $9.01{\pm}0.24{\mu}mol/L$ was $4.64{\pm}3.98{\mu}mol/L$ (P=0.005), and the PDV group was $9.41{\pm}0.27{\mu}mol/La$ (p=0.005), and thus total antioxidant activity was increased statistically significantly In a multiple comparison test, the PDV group showed the highest total antioxidant activity (p<0.0001). Conclusion: The result of the assessment of the antioxidant effect of vitamin C and deferoxamine on paraquat-induced cytotoxicity showed that in regard to cytotoxicity, SOD activity and TAS measurement, the best result was observed in the PDV group. Therefore, it was found that vitamin C and deferoxamine were effective antioxidants for the paraquat-induced cytotoxicity, and it suggests that the administration of deferoxamine followed by vitamin C may improve their antioxidant effect more.

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L-carnitine에 의한 인간대장암세포주 증식억제 및 산화적손상 기전 규명 (The Anti-Proliferation and Oxidative Damage-Related Mechanism of L-Carnitine in Human Colorectal Cancer Cells)

  • 이주연;박정란;장애라;양세란
    • 한국식품위생안전성학회지
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    • 제34권3호
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    • pp.303-308
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    • 2019
  • L-carnitine은 라이신과 메티오닌으로 생합성되며 골격근과 심근을 포함한 다양한 동물조직에서 발견된다. L-carnitine이 포함된 식품으로는 양고기, 소고기, 돼지고기 등이 있고 근육발달에 도움을 주며 뼈를 강화하거나 대사작용을 도와주는 기능을 하여 영양 보조제로 많이 섭취하는 것으로 알려져 있다. 최근 L-carnitine은 제 2형 당뇨병, 골다공증, 대사성 신경증후군 등의 다양한 질병의 약물로도 연구 되고 있으며 암에서는 치료 보조제로 개발되어있다. 하지만 대장암에서의 L-carnitine에 대한 효과 및 기전에 대해서는 명확하지 않고 연구된 바가 없기 때문에 본 연구에서 저자들은 L-carnitine의 효능을 인간대장암세포주 HCT116에서 규명하고자 하였다. L-carnitine은 세포 내 활성산소종 (ROS)를 높은 수준으로 증가시켜 세포 증식을 억제하였다. 또한, 세포 증식과 죽음에 관련한 단백질 ERK1/2와 p38을 유의적으로 활성화 시킨다는 것을 입증하였다. 이때, ERK1/2 억제제(PD98059)를 처치하여 ERK1/2의 활성화가 활성산소종 발생 및 세포사멸에 중요하다는 것을 밝혔다. 따라서, 본 연구 결과는 L-carnitine이 대장암세포주의 증식을 억제 할 수 있고 이는 대장암의 치료에 있어 잠재적인 치료 물질이 될 수 있음을 시사하며 이 과정에 관여하는 신호전달기전을 조사하여 항암의 치료기전에서 활성산소종이나 ERK1/2, p38 단백질의 활성화의 중요성을 제시하였다.

핵융합 배가스 중 CQ4와 Q2O 처리공정 제안 및 HAZOP 분석 (Process Suggestion and HAZOP Analysis for CQ4 and Q2O in Nuclear Fusion Exhaust Gas)

  • 정우찬;정필갑;김정원;문흥만;장민호;윤세훈;우인성
    • Korean Chemical Engineering Research
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    • 제56권2호
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    • pp.169-175
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    • 2018
  • 본 연구는 핵융합 배가스 중 삼중수소가 포함된 화합물인 메탄($CQ_4$) 및 물($Q_2O$)로부터 수소동위원소를 회수하기 위한 공정에 관한 것이다(Q는 수소, 중수소, 삼중수소). 수증기-메탄 개질반응과 수성가스 전환반응을 이용하여 $CQ_4$$Q_2O$$Q_2$로 변환시키고, 후속하는 팔라듐 분리막으로 생성된 $Q_2$를 회수한다. 본 연구에서는 $CQ_4$$Q_2O$ 중 하나의 물질인 $CH_4$$H_2O$로부터 수소 회수를 위해 촉매반응기, 팔라듐 분리막, 순환펌프로 구성된 순환루프를 적용하였다. 촉매반응온도 및 순환유량을 변화시켜가며 $CH_4$$H_2O$의 전환율을 측정하였다. $CH_4$ 중 수소 회수는 촉매반응온도 $650^{\circ}C$, 순환유량 2.0 L/min 조건에서 99% 이상의 $CH_4$ 전환율을확인하였고, $H_2O$ 중수소 회수는촉매반응온도 $375^{\circ}C$, 순환유량 1.8 L/min 조건에서 96% 이상의 $H_2O$ 전환율을 확인하였다. 이와 더불어, 향후 핵융합 실증로(K-DEMO)에서의 $CQ_4$ 발생량을 예측하고, 이에 대한 처리공정을 제안하였으며, HAZOP (Hazard and Operability) 분석을 실시하여 공정의 위험요소와 운전상의 문제점을 도출하고 해결방안을 제시하였다.