• Title/Summary/Keyword: Response Localization

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Iron-Saturated Lactoferrin Stimulates Cell Cycle Progression through PI3K/Akt Pathway

  • Lee, Shin-Hee;Pyo, Chul-Woong;Hahm, Dae Hyun;Kim, Jiyoung;Choi, Sang-Yun
    • Molecules and Cells
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    • v.28 no.1
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    • pp.37-42
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    • 2009
  • Iron binding lactoferrin (Lf) is involved in the control of cell cycle progression. However, the molecular basis underlying the effects of Lf on cell cycle control, as well as its target genes, remains incompletely understood. In this study, we have demonstrated that a relatively low level of ironsaturated Lf, Lf($Fe^{3+}$), can stimulate S phase cell cycle entry, and requires Akt activation in MCF-7 cells. Lf($Fe^{3+}$) immediately induced Akt phosphorylation at Ser473, which subsequently induced the phosphorylation of two G1-checkpoint Cdk inhibitors, $p21^{Cip/WAF1}$ and $p27^{kip1}$. The Lf($Fe^{3+}$)-induced phosphorylation of Cdk inhibitors impaired their nuclear import behavior, thereby inducing cell cycle progression. However, the treatment of cells with a PI3K inhibitor, LY294002, almost completely blocked Lf($Fe^{3+}$)-stimulated cell cycle progression. LY294002 treatment abrogated Lf($Fe^{3+}$)-induced Akt activation, and prevented the cytoplasmic localization of $p27^{kip1}$. Higher levels of $p21^{Cip/WAF1}$ were also detected in the cytoplasmic sub-cellular compartment as a measure of cellular response to Lf($Fe^{3+}$). Consequently, the degree of phosphorylation of retinoblastoma protein was enhanced in response to Lf($Fe^{3+}$). Therefore, we conclude that Lf($Fe^{3+}$), as a potential antagonist of Cdk inhibitors, can facilitate the functions of E2F during progression to S phase via the Akt signaling pathway.

Changes in Cell Ca2+ Distribution in Loquat Leaves and Its Effects on Cold Tolerance

  • Zheng, Guohua;Pan, Dongming;Niu, Xianqian;Wu, Hanwen;Zhang, Jinbiao
    • Horticultural Science & Technology
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    • v.32 no.5
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    • pp.607-613
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    • 2014
  • Calcium has been associated with improved cold tolerance in many crops. The aim of this study was to investigate the changes in leaf cell $Ca^{2+}$ distribution and cell organelle ultrastructure of loquat (Eriobotrya japonica Lindl.) plants in response to cold stress at $-3^{\circ}C$, using transmission electron microscopy (TEM). Two loquat accessions, Zaozhong 6 (a commercial cultivar) and oakleaf loquat (a wild relative) were used. Cold tolerance, as measured by leaf browning rate, was higher in oakleaf plants, and calcium treatment improved cold tolerance in both species. Cold stress first induced inward transport of $Ca^{2+}$ from the intracellular space. Then, the imported $Ca^{2+}$ was aggregated around the chloroplast membrane, finally entering the chloroplast. This pattern of $Ca^{2+}$ distribution in leaf cells occurred earlier in Zaozhong 6 than in the wild loquat. With increasing time of cold exposure, the chloroplast membranes of Zaozhong 6 leaves were damaged, blurred and even disappeared, while those of wild oakleaf loquat leaves maintained their structure longer. In Zaozhong 6, cold stress induced a clear cavity between poorly structured granal thylakoids and vesicles appearing inside the chloroplast, while in oakleaf leaves cold stress had little effect on the ultrastructure of chloroplasts (although chloroplast membranes looked blurred). Loquat leaves accumulated free calcium ions around chloroplasts in response to cold stress, with earlier calcium accumulation occurring in the cold-sensitive cultivar Zaozhong 6 than in wild oakleaf loquat. These results demonstrate that these two loquat species have differences in both cold tolerance and calcium accumulation dynamics.

Histone Deacetylase-3/CAGE Axis Targets EGFR Signaling and Regulates the Response to Anti-Cancer Drugs

  • Kim, Hyuna;Kim, Youngmi;Goh, Hyeonjung;Jeoung, Dooil
    • Molecules and Cells
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    • v.39 no.3
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    • pp.229-241
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    • 2016
  • We have previously reported the role of miR-326-HDAC3 loop in anti-cancer drug-resistance. CAGE, a cancer/testis antigen, regulates the response to anti-cancer drug-resistance by forming a negative feedback loop with miR-200b. Studies investigating the relationship between CAGE and HDAC3 revealed that HDAC3 negatively regulated the expression of CAGE. ChIP assays demonstrated the binding of HDAC3 to the promoter sequences of CAGE. However, CAGE did not affect the expression of HDAC3. We also found that EGFR signaling regulated the expressions of HDAC3 and CAGE. Anti-cancer drug-resistant cancer cell lines show an increased expression of $pEGFR^{Y845}$. HDAC3 was found to negatively regulate the expression of $pEGFR^{Y845}$. CAGE showed an interaction and co-localization with EGFR. It was seen that miR-326, a negative regulator of HDAC3, regulated the expression of CAGE, $pEGFR^{Y845}$, and the interaction between CAGE and EGFR. miR-326 inhibitor induced the binding of HDAC3 to the promoter sequences in anti-cancer drug-resistant $Malme3M^R$ cells, decreasing the tumorigenic potential of $Malme3M^R$ cells in a manner associated with its effect on the expression of HDAC3, CAGE and $pEGFR^{Y845}$. The down-regulation of HDAC3 enhanced the tumorigenic, angiogenic and invasion potential of the anti-cancer drug-sensitive Malme3M cells in CAGE-dependent manner. Studies revealed that $PKC{\delta}$ was responsible for the increased expression of $pEGFR^{Y845}$ and CAGE in $Malme3M^R$ cells. CAGE showed an interaction with $PKC{\delta}$ in $Malme3M^R$ cells. Our results show that HDAC3-CAGE axis can be employed as a target for overcoming resistance to EGFR inhibitors.

Recent Update of Advanced Imaging for Diagnosis of Cardiac Sarcoidosis: Based on the Findings of Cardiac Magnetic Resonance Imaging and Positron Emission Tomography

  • Chang, Suyon;Lee, Won Woo;Chun, Eun Ju
    • Investigative Magnetic Resonance Imaging
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    • v.23 no.2
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    • pp.100-113
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    • 2019
  • Sarcoidosis is a multisystem disease characterized by noncaseating granulomas. Cardiac involvement is known to have poor prognosis because it can manifest as a serious condition such as the conduction abnormality, heart failure, ventricular arrhythmia, or sudden cardiac death. Although early diagnosis and early treatment is critical to improve patient prognosis, the diagnosis of CS is challenging in most cases. Diagnosis usually relies on endomyocardial biopsy (EMB), but its diagnostic yield is low due to the incidence of patchy myocardial involvement. Guidelines for the diagnosis of CS recommend a combination of clinical, electrocardiographic, and imaging findings from various modalities, if EMB cannot confirm the diagnosis. Especially, the role of advanced imaging such as cardiac magnetic resonance (CMR) imaging and positron emission tomography (PET), has shown to be important not only for the diagnosis, but also for monitoring treatment response and prognostication. CMR can evaluate cardiac function and fibrotic scar with good specificity. Late gadolinium enhancement (LGE) in CMR shows a distinctive enhancement pattern for each disease, which may be useful for differential diagnosis of CS from other similar diseases. Effectively, T1 or T2 mapping techniques can be also used for early recognition of CS. In the meantime, PET can detect and quantify metabolic activity and can be used to monitor treatment response. Recently, the use of a hybrid CMR-PET has introduced to allow identify patients with active CS with excellent co-localization and better diagnostic accuracy than CMR or PET alone. However, CS may show various findings with a wide spectrum, therefore, radiologists should consider the possible differential diagnosis of CS including myocarditis, dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy, amyloidosis, and arrhythmogenic right ventricular cardiomyopathy. Radiologists should recognize the differences in various diseases that show the characteristics of mimicking CS, and try to get an accurate diagnosis of CS.

Matrix metalloproteinases: expression and regulation in the endometrium during the estrous cycle and at the maternal-conceptus interface during pregnancy in pigs

  • Inkyu Yoo;Soohyung Lee;Yugyeong Cheon;Hakhyun Ka
    • Animal Bioscience
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    • v.36 no.8
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    • pp.1167-1179
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    • 2023
  • Objective: Matrix metalloproteinases (MMPs) are a family of endoproteases produced by various tissues and cells and play important roles in angiogenesis, tissue repair, immune response, and endometrial remodeling. However, the expression and function of MMPs in the pig endometrium during the estrous cycle and pregnancy have not been fully elucidated. Thus, we determined the expression, localization, and regulation of MMP2, MMP8, MMP9, MMP12, and MMP13 in the endometrium throughout the estrous cycle and at the maternal-conceptus interface during pregnancy in pigs. Methods: Endometrial tissues during the estrous cycle and pregnancy and conceptus and chorioallantoic tissues during pregnancy were obtained and the expression of MMPs was analyzed. The effects of steroid hormones and cytokines on the expression of MMPs were determined in endometrial explant cultures. Results: Expression levels of MMP12 and MMP13 changed during the estrous cycle, while expression of MMP2, MMP9, MMP12, and MMP13 changed during pregnancy. Expression of MMP2, MMP8, and MMP13 mRNAs was cell type-specific at the maternal-conceptus interface. Gelatin zymography showed that enzymatically active MMP2 was present in endometrial tissues. In endometrial explant cultures, estradiol-17β induced the expression of MMP8 and MMP12, progesterone decreased the expression of MMP12, interleukin-1β increased the expression of MMP2, MMP8, MMP9, and MMP13, and interferon-γ increased the expression of MMP2. Conclusion: These results suggest that MMPs expressed in response to steroids and cytokines play an important role in the establishment and maintenance of pregnancy by regulating endometrial remodeling and processing bioactive molecules in pigs.

Ammonium Excess Promotes Proline Synthesis but Inhibits Glutathione Synthesis in Oilseed Rape (Brassica napus L.)

  • Hyunjae Lee;Seon-Hye Baek;Tae-Hwan Kim
    • Journal of The Korean Society of Grassland and Forage Science
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    • v.43 no.2
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    • pp.109-115
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    • 2023
  • Ammonium (NH4+) serves as a nitrogen source, but its elevated levels can hinder plant growth and production. Excess NH4+ with α-ketoglutarate is assimilated into glutamate, a precursor of proline and glutathione (GSH). This study aimed to investigate the effects of excessive NH4+ on the regulation of proline and GSH synthesis. Detached leaves from oilseed rape (Brassica napus L.) were fed with 0, 50, 100, 500, and 1000 mM NH4Cl for 16 h. As the NH4+ concentrations increased, the leaves exhibited progressive wilting and yellowing. Furthermore, total carotenoid and chlorophyll concentrations declined in response to all NH4+ treatments, with the lowest levels observed in 1000 mM NH4+ treatment. Hydrogen peroxide (H2O2) concentration showed a minor increase at low NH4+ concentration (50 and 100 mM) treatments but a significant increase at high NH4+ (500 and 1000 mM), which was consistent with the localization of H2O2. Amino acid concentrations increased with increasing in NH4+ concentration, while the protein concentration displayed the opposite trend. Proline and cysteine concentrations exhibited a gradual increase in response to increasing NH4+ concentrations. However, GSH concentrations rose only in the 50 mM NH4+ treatment and decreased in the 500 and 1000 mM NH4+ treatments. These results indicate that excessive NH4+ is primarily assimilated into proline, while GSH synthesis is adversely affected.

Caveolin-1, Through its Ability to Negatively Regulate TLR4, is a Crucial Determinant of MAPK Activation in LPS-challenged Mammary Epithelial Cells

  • Wang, Xiao-Xi;Wu, Zheng;Huang, Hui-Fang;Han, Chao;Zou, Wei;Liu, Jing
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2295-2299
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    • 2013
  • Background: To explore the role of caveolin-1(CAV-1) gene silencing on MAPK activation in lipopolysaccharide (LPS)-challenged human mammary epithelial cells. Methods: We established a MCF-10ACE of CAV-1 gene silencing from human mammary epithelial cell line MCF-10A by RNAi technology. DNA Microarray were used to detect the expression of inflammation-associated genes in MCF10ACE. Western blotting was used to examine the activation of MAPK in lipopolysaccharide(LPS)-challenged MCF-10A and MCF-10ACE. Moreover, immunofluorescence and Western bloting were performed to detect the co-localization of CAV-1 and toll-like receptor 4 (TLR4) in human mammary epithelial cells. Results: MCF-10ACE exhibited significant increases in inflammation-associated gene expression, especially IL-6 (~7-fold) and IL6R (~17-fold). In addition, LPS-induced p38 MAPK and JNK MAPK activation was significantly increased in MCF-10ACE. Furthermore, CAV-1 co-localized with TLR4 and appeared a negative correlation trend. Conclusion: CAV-1 gene silencing promotes MAPK activation via TLR4 signaling in human mammary epithelial cells response to LPS.

Atomistic simulation of surface passivated wurtzite nanowires: electronic bandstructure and optical emission

  • Chimalgi, Vinay U.;Nishat, Md Rezaul Karim;Yalavarthi, Krishna K.;Ahmed, Shaikh S.
    • Advances in nano research
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    • v.2 no.3
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    • pp.157-172
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    • 2014
  • The three-dimensional Nano-Electronic Modeling toolkit (NEMO 3-D) is an open source software package that allows the atomistic calculation of single-particle electronic states and optical response of various semiconductor structures including bulk materials, quantum dots, impurities, quantum wires, quantum wells and nanocrystals containing millions of atoms. This paper, first, describes a software module introduced in the NEMO 3-D toolkit for the calculation of electronic bandstructure and interband optical transitions in nanowires having wurtzite crystal symmetry. The energetics (Hamiltonian) of the quantum system under study is described via the tight-binding (TB) formalism (including $sp^3$, $sp^3s^*$ and $sp^3d^5s^*$ models as appropriate). Emphasis has been given in the treatment of surface atoms that, if left unpassivated, can lead to the creation of energy states within the bandgap of the sample. Furthermore, the developed software has been validated via the calculation of: a) modulation of the energy bandgap and the effective masses in [0001] oriented wurtzite nanowires as compared to the experimentally reported values in bulk structures, and b) the localization of wavefunctions and the optical anisotropy in GaN/AlN disk-in-wire nanowires.

Modeling of individual head-related impulse responses using a set of general basis functions (보편적인 기저함수를 이용한 개인의 머리전달함수 모델링)

  • Hwang, Sung-Mok;Park, Young-Jin;Park, Youn-Sik
    • Proceedings of the Korean Society for Noise and Vibration Engineering Conference
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    • 2007.11a
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    • pp.1430-1436
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    • 2007
  • A principal components analysis (PCA) of the median head-related impulse responses (HRIRs) in the CIPIC HRTF database reveals that the individual HRIRs can be adequately reconstructed by a linear combination of 12 orthonormal basis functions. These basis functions can be used generally to model arbitrary HRIRs, which are not included in the process to obtain the basis functions. To clarify whether these basis functions can be used to model other set of arbitrary HRIRs, an numerical error analysis for modeling and a series of subjective listening tests were carried out using the measured and modeled HRIRs. The results showed that the set of individual HRIRs, which were measured in our lab using different measurement conditions, techniques, and source positions, can be well modeled with reasonable accuracy. Furthermore, all subjects reported not only the accurate vertical perception but also the front-back discrimination with the modeled HRIRs based on 12 basis functions. However, as less basis functions were used for HRIR modeling, the modeling accuracy and localization performance deteriorated.

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A Trial of Data Editing Using Fellegi-Holt Techniques and Its Analysis (Fellegi-Holt 기법을 이용한 에디팅의 시도 및 분석)

  • Lee, Eui-Kyoo;Shim, Kyu-Ho
    • The Korean Journal of Applied Statistics
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    • v.22 no.4
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    • pp.697-707
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    • 2009
  • In actual statistical surveys, the inconsistencies within the record are often occurred due to incorrect response. The users may be confused and statistical agencies may have a problem of reliability on statistical data in this case. It is needed to detect and correct the unconvinced record without any special reasons. However, it is not simple to determine which item should be corrected in every failed record. In this paper we briefly introduce Fellegi-Holt method, apply to a business survey, and then discuss the problems for this trial editing.