• Archives of Pharmacal Research
• /
• 제27권4호
• /
• pp.361-370
• /
• 2004

The discovery of insulin receptor substrate (IRS) proteins and their role to link cell surface receptors to the intracellular signaling cascades is a key step to understanding insulin and insulin-like growth factor (IGF) action. Moreover, IRS-proteins coordinate signals from the insulin and IGF receptor tyrosine kinases with those generated by proinflammatory cytokines and nutrients. The IRS2-branch of the insulin/IGF signaling cascade has an important role in both peripheral insulin response and pancreatic $\beta$-cell growth and function. Dysregulation of IRS2 signaling in mice causes the failure of compensatory hyperinsulinemia during peripheral insulin resistance. IRS protein signaling is down regulated by serine phosphorylation or protea-some-mediated degradation, which might be an important mechanism of insulin resistance during acute injury and infection, or chronic stress associated with aging or obesity. Under-standing the regulation and signaling by IRS1 and IRS2 in cell growth, metabolism and survival will reveal new strategies to prevent or cure diabetes and other metabolic diseases.

• Journal of Korean Neurosurgical Society
• /
• 제29권6호
• /
• pp.731-737
• /
• 2000

목 적 : 종양세포의 세포면에서는 성장인자 수용체들이 과발현되고 이들이 성장인자들과 결합함으로서 세포의 성장을 촉진하게 된다. 원발성 악성 뇌종양에 대한 새로운 치료법 중 하나가 면역독소를 사용하는 방법이다. 독소는 대상 세포의 세포면에 있는 수용체를 통해 세포질로 이행되며, 면역독소가 선택적인 항종양작용을 나타내기 위해서는 수용체가 과발현되어야 한다. 강력한 세포독성의 효과가 있음에도 불구하고 면역독소를 환자에 투여하였을 때 종양을 완치시키지는 못하였는데, 면역독소의 효과에 영향을 미치는 여러 인자들에 대한 더 많은 연구가 요구된다. 이러한 연구에 사용되어질 뇌종양세포주들에서 성장인자수용체들의 발현 여부를 알아보기 위해 본 연구를 시행하였다. 대상 및 방법 : 한 개의 수모세포종 세포주(Daoy)와 두 개의 교모세포종 세포주(U373 MG, T98 G)에서, transferrin 수용체, insulin-like growth factor-1 수용체, 그리고 interleukin-4 수용체들의 발현을 flow cytometric analysis를 이용하여 조사하였다. 결 과 : Transferrin 수용체와 interleukin-4 수용체는 Daoy, U373 MG, 그리고 T98 G 모두에서 발현되었다. Insulin-like growth factor-1 수용체는 Daoy와 U373 MG에서는 발현되었지만 T98 G에서는 발현되지 않았다. 결 론 : Transferrin 수용체와 interleukin-4 수용체는 면역독소 치료에 적합한 것으로 보인다. 본 실험의 결과는 상기의 세포주를 사용하여 면역독소와 관련된 실험을 하는데 참고가 되어야하며, 면역독소 치료에 있어서 적절한 면역독소를 선택하는 문제 등 치료 모델을 확립하는데 고려되어야 할 것이다.

• 한국응용곤충학회지
• /
• 제61권1호
• /
• pp.85-90
• /
• 2022

인슐린(insulin)과 insulin-like growth factor-1 (IGF-1)은 척추동물에서 대사, 생장, 수명 등의 여러 생리대사를 조절하는 중요한 호르몬이다. 곤충에서도 IGF-1과 구조적으로 유사한 insulin-like peptide (ILP)들이 존재하며 이들이 곤충 생리 조절에 중요하게 관여함이 밝혀졌다. 이번 총설에서 곤충 ILP 및 초파리(Drosophila melanogaster) 유전체 분석을 통해 척추동물에 존재하는 인슐린 및 IGF-1 수용체 신호전달계와 유사하다고 확인된 ILP 수용체 신호전달계에 대해 설명하고자 한다. 추가적으로, 곤충 체내의 영양 상태에 따라 조절되는 뇌에서의 ILP의 합성과 분비, ILP에 의한 대사의 생리적 조절에 대해 논한다. 또한 ILP가 생장, 발달, 생식, 휴면에 기여하는 바도 논의하고, 마지막으로 ILP 수용체 신호전달계 제어를 통한 해충 방제에의 이용 가능성에 대해 제안하고자 한다.

• Asian-Australasian Journal of Animal Sciences
• /
• 제33권10호
• /
• pp.1674-1682
• /
• 2020

Objective: This study aimed to elucidate the effect of miR-140 on the proliferation of porcine fetal fibroblasts (PFFs) and identify the target genes of miR-140 in PFFs. Methods: In this study, bioinformatics software was used to predict and verify target genes of miR-140. Quantitative polymerase chain reaction and western blot were used to detect the relationship between miR-140 and its target genes in PFFs. Dual luciferase reporter gene assays were performed to assess the interactions among miR-140, type 1 insulin-like growth factor receptor (IGF1R), and SRY-box 4 (SOX4). The effect of miR-140 on the proliferation of PFFs was measured by CCK-8 when PFFs were transfected with a miR-140 mimic or inhibitor. The transcription factor SOX4 binding to promoter of IGF1R was detected by chromatin immunoprecipitation assay (ChIP). Results: miR-140 directly targeted IGF1R and inhibited proliferation of PFFs. Meanwhile, miR-140 targeted transcription factor SOX4 that binds to promoter of porcine IGF1R to indirectly inhibit the expression of IGF1R. In addition, miR-140 inhibitor promoted PFFs proliferation, which is abrogated by SOX4 or IGF1R knockdown. Conclusion: miR-140 inhibited PFFs proliferation by directly targeting IGF1R and indirectly inhibiting IGF1R expression via SOX4, which play an important role in the development of porcine fetal.

• Natural Product Sciences
• /
• 제27권2호
• /
• pp.134-139
• /
• 2021

A new cipadesin limonoid, i.e. 3-epi-cipadonoid C (1), and a new tirucallane triterpene, i.e. hispidol B 3-palmitate (3), have been isolated from the seeds and fruit peels extract of Sandoricum koetjape, respectively. Along with these compounds the known limonoid, cipaferen G (2), and two pentacyclic triterpenes, bryonolic (4) and bryononic (5) acids, were also isolated. The strucrures of the new compounds were elucidated by the analysis of NMR and mass spectral data. Compounds 1 - 5 were evaluated as the inhibitor of receptor tyrosine kinases (EGFR, Epidermal Growth Factor Receptor; HER2, HER4, Human Epidermal growth factor Receptor 2, -4; IGFR, Insulin-like Growth Factor Receptor; InsR, Insulin Receptor; KDR, Kinase insert Domain Receptor; PDGFRα, and PDGFRβ, Platelet-Derived Growth Factor Receptor-α and -β). The results showed only 1 and 3 that have weak activity against InsR.

• BMB Reports
• /
• 제52권1호
• /
• pp.70-85
• /
• 2019

Reduction of insulin/insulin-like growth factor 1 (IGF1) signaling (IIS) extends the lifespan of various species. So far, several longevity mouse models have been developed containing mutations related to growth signaling deficiency by targeting growth hormone (GH), IGF1, IGF1 receptor, insulin receptor, and insulin receptor substrate. In addition, p70 ribosomal protein S6 kinase 1 (S6K1) knockout leads to lifespan extension. S6K1 encodes an important kinase in the regulation of cell growth. S6K1 is regulated by mechanistic target of rapamycin (mTOR) complex 1. The v-myc myelocytomatosis viral oncogene homolog (MYC)-deficient mice also exhibits a longevity phenotype. The gene expression profiles of these mice models have been measured to identify their longevity mechanisms. Here, we summarize our knowledge of long-lived mouse models related to growth and discuss phenotypic characteristics, including organ-specific gene expression patterns.

• Fisheries and Aquatic Sciences
• /
• 제21권2호
• /
• pp.4.1-4.5
• /
• 2018

Insulin-like growth factors (IGFs), along with IGF-binding protein and IGF receptor, are well-known regulators in the growth and survival of vertebrates. In this study, we investigated the involvement of IGFs and protein variation during embryonic development of the olive flounder (Paralichthys olivaceus). Morphological stages were divided into six main developments as blastula, gastrula, cephalization, cranial regionalization, tail lift, and hatch. During embryonic development, protein variation was investigated using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrospray ionization quadrupole time-of-flight mass spectrometry/mass spectrometry. In addition, the mechanism of signaling of IGF-I receptor was examined using immuno-blot analysis. We found marked changes in protein expression at four stages of embryonic development and identified proteins as belonging to the vitellogenin 2 family. As development progresses, expression of IGF-II, phosphotyrosine, and phospho-Akt increased, while expression of growth factor receptor-bound protein 2 (GRB2) and one of guanine-nucleotide-binding proteins (Ras) decreased. These results provide basic information on the IGF system in the embryonic development of the olive flounder.

• BMB Reports
• /
• 제48권6호
• /
• pp.342-347
• /
• 2015

The expression of epidermal growth factor receptor (EGFR) is an important diagnostic marker for triple-negative breast cancer (TNBC) cells, which lack three hormonal receptors: estrogen and progesterone receptors as well as epidermal growth factor receptor 2. EGFR transactivation can cause drug resistance in many cancers including TNBC, but the mechanism underlying this phenomenon is poorly defined. Here, we demonstrate that insulin treatment induces EGFR activation by stimulating the interaction of EGFR with insulin-like growth factor receptor 1 (IGF-1R) in the MDA-MB-436 TNBC cell line. These cells express low levels of EGFR, while exhibiting high levels of IGF-1R expression and phosphorylation. Low-EGFRexpressing MDA-MB-436 cells show high sensitivity to insulinstimulated cell growth. Therefore, unexpectedly, insulin stimulation induced EGFR transactivation by regulating its interaction with IGF-1R in low-EGFR-expressing TNBC cells. [BMB Reports 2015; 48(6): 342-347]

• 한국식품영양과학회지
• /
• 제32권3호
• /
• pp.437-443
• /
• 2003

선행연구에서 라이코펜이 HT-29세포의 증식을 억제하는 것을 관찰하였기 때문에 본 연구는 그 기전을 연구하기 위하여 수행되 었다. 라이코펜이 HT-29 세포의 사멸을 유도하는지 조사하기 위해서 여러 농도의 라이코펜이 포함된 배지에서 세포를 4일 동안 배양하였다. 라이코펜 농도의 증가에 따라 사멸되는 세포에서 나타나는 특징의 하나인 DNA fragmentation이 증가하는 것을 관찰하였다. Western blot을 수행하여 얻은 결과에 의하면 라이코펜이 IGF-IR, IRS-1, PI3K, Akt와 같은 IGF-IR pathway에 속하는 단백질의 수준을 감소시켰다. IGF-IR의 인산화를 유도하기 위해서 라이코펜이 포함된 배지에서 세포를 배양하고 IGF-I을 첨가하여 0, 5, 10, 60분간 배양한 다음 IGF-IR antibody를 이용하여 immunoprecipitation을 수행하였다. 라이코펜은 IGF-I에 의한 IGF-IR, IRS-1의 인산화와 IGF-IR와 PI3K의 결합을 감소하고 인산화된 Akt를 감소시켰다. 이와 같은 IGF-IR signaling의 억제는 이 대장암세포에 존재하는 IGF-II의 autocrine loop을 억제하는 원인이 될 수 있어, 라이코펜의 암세포증식을 억제하는 기전 중의 하나가 될 수 있다. 라이코펜은 토마토와 그 가공품에 많이 존재하는 물질로 자연적인 식사를 통해 많이 섭취할 수 있는 물질이다. 라이코펜의 항암 기전을 밝혀냄으로써 미래 암예방과 치료를 위한 중요한 기능성 영양소를 생산할 수 있는 기초를 마련해줄 수 있을 것으로 기대된다.

• Journal of Periodontal and Implant Science
• /
• 제25권3호
• /
• pp.518-528
• /
• 1995

The immunohistochemical study has been performed on the distribution of receptors for various growth factors in the newly forming granulation tissues following the guided tissue regeneration procedures. Two specimens from 2 different patients were collected from the newly forming granulation tissues at 2 weeks following GTR procedures using Gore-tex menbrane and rubber dam, respectively. For immunohistochemical localization of each recptor, anti-platelet-derived growth factor $receptor-{\alpha}$, anti-platelet-derived growth factor $receptor-{\beta}$. anti-insulin-like growth factor receptor, anti-basic fibroblast growth factor receptor, anti-transforming growth $factor-{\beta}$ receptor and anti-fibronectin receptor were incubated onto the specimens as primary antibodies. After the reaction, FITC-conjugated second antibodies have been applied. When the total numbers of immunoreactive cells and the true positive cells were counted, there were high variability among receptors tested in the present study. The mean number of immunoreactive cells were highest in the case for anti-IFG-1 receptor. However the number of true positive cells were highest in the case for $TGF-{\beta}$ receptor. The present investigation indicated that the receptor for $TGF-{\beta}$ were stongly expressed in the newly forming granulation tissues following the guided tissue regeneration therapy.