• Title/Summary/Keyword: Insulin-like growth factor-1

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Insulin-like Growth Factor-1 (IGF-1) Gene Expression Is Enhanced under Hypothermia but Depressed under Additional Ischemic Stimulus

  • Kwon, O-Yu;Kwon, Kisang;Yu, Kweon;Kim, Seung-Whan
    • Biomedical Science Letters
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    • v.21 no.2
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    • pp.126-130
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    • 2015
  • There are several studies that show hypothermia improves cellular ischemia damages on experimental and clinical bases. However, its exact molecular mechanisms are unclear. In this study, we demonstrate that hypothermia induced insulin-like growth factor 1 (IGF1) gene expression, and its expression was dramatically decreased under ischemic insults. It was also demonstrated that hypothermia activated endoplasmic reticulum (ER) stress sensors especially both the phosphorylation of $eIF2{\alpha}$ (eukaryotic translation initiation factor 2 alpha) and ATF6 (activating transcription factor-6) proteolytic cleavage. However, the factors of apoptosis and autophagy were not associated with hypothermia. We suggest that hypothermia-treated IGF1 gene expression after ischemia may show a good possibility for the development of treatments and diagnostic methods in cerebral ischemic damages.

Knock-in Vector for Expression of Insulin-like Growth Factor 1 on the Bovine β-casein Gene Locus (소 β-casein 유전자 영역에서 소 Insulin-like Growth Factor 1을 생산하기 위한 Knock-in Vector)

  • Kim, Sang Young;Park, Da Som;Kim, Se Eun;Koo, Deog-Bon;Kang, Man-Jong
    • Reproductive and Developmental Biology
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    • v.41 no.3
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    • pp.51-55
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    • 2017
  • The production of therapeutic protein from transgenic domestic animal is the major technology of biotechnology. Insulin-like growth factor-1 (IGF-1) is known to play an important role in the growth of the animal. The objective of this study is construction of knock-in vector that bovine IGF-1 gene is inserted into the exon 7 locus of ${\beta}$-casein gene and expressed using the gene regulatory DNA sequence of bovine ${\beta}$-casein gene. The knock-in vector consists of 5' arm region (1.02 kb), bIGF-1 cDNA, CMV-EGFP, and 3' arm region (1.81 kb). To express bIGF-1 gene as transgene, the F2A sequence was fused to the 5' terminal of bIGF-1 gene and inserted into exon 7 of the ${\beta}$-casein gene. As a result, the knock-in vector is confirmed that the amino acids are synthesized without termination from the ${\beta}$-casein exon 7 region to the bIGF-1 gene by DNA sequence. These knock-in vectors may help to create transgenic dairy cattle expressing bovine bIGF-1 protein in the mammary gland via the expression system of the bovine ${\beta}$-casein gene.

Hypothermia Regulates Insulin-like Growth Factor 1 Gene Expression in PC12 Cells

  • Yoo, Bo-Kyung;Kwon, Kisang;Lee, Eun Ryeong;Kim, Seung-Whan;Yu, Kweon;Kwon, O-Yu
    • Biomedical Science Letters
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    • v.23 no.1
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    • pp.39-43
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    • 2017
  • In this study, we evaluated the effects of various hypothermic conditions ($32^{\circ}C$), including lithium chloride treatment, on insulin-like growth factor 1 (IGF-1) gene expression in PC12 cells. The results show that short-term hypothermic treatment (<1 day) resulted in relatively higher IGF-1 gene expression than did longer-term treatment (>1 day). Repeated switching between normal temperature and hypothermia every 2 h increased IGF-1 gene expression approximately 3-4-fold. These findings indicate that hypothermia dynamically regulates IGF-1 gene expression. This study could be helpful for the development of treatment and diagnostic strategies for ischemia.

Hypopituitarism and Legg-Calve-Perthes disease related to difficult delivery

  • Bas, Veysel Nijat;Uytun, Salih;Vurdem, Umit Erkan;Torun, Yasemin Altuner
    • Clinical and Experimental Pediatrics
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    • v.58 no.7
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    • pp.270-273
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    • 2015
  • Legg-Calve-Perthes (LCP) disease is characterized by idiopathic avascular osteonecrosis of the epiphysis of the femur head. The main factor that plays a role in the etiology of the disease is decreased blood flow to the epiphysis. Many predisposing factors have been suggested in the etiology of LCP disease, and most have varying degrees of effects. Here we present the case of a boy aged 4 years and 10 months with complaints of short stature and a diagnosis of multiple hypophyseal hormone deficiency, in whom LCP disease and difficult birth-related pituitary stalk interruption syndrome were identified by anamnesis. The present case revealed that LCP disease and hypophyseal hormone deficiency could be secondary to difficult birth and that LCP disease could be secondary to insulin-like growth factor 1 deficiency. Additionally, to the best of our knowledge there is no published case on the relation between LCP disease and insulin-like growth factor 1 deficiency. Therefore, we believe that this case is worthy of presentation.

Growth Factor Receptor Expression on Brain Tumor Cell Lines : Preliminary Study for in vitro and in vivo Experiments of Immunotoxin Therapy (뇌종양세포주에서의 성장인자수용체의 발현 : 면역독소 치료의 연구를 위한 예비실험)

  • im, Ki-Uk;Ni, Hsiao-Tzu;Low, Walter C.;Hall, Walter A.
    • Journal of Korean Neurosurgical Society
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    • v.29 no.6
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    • pp.731-737
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    • 2000
  • Objective : Growth factor receptors on the tumor cells are known to be expressed highly allowing the tumor cells to bind growth factors to stimulate cellular division. Immunotoxin therapy is one of the novel approaches to the primary malignant brain tumor, and expression of cell-surface receptor is essential for the immunotoxin to have specific anti-tumor activity. Despite promising cytotoxic activity of immunotoxin, tumor responses are not curative on clinical trials, and additional studies are needed regarding various factors influencing the efficacy of the immunotoxin. The purpose of this study is to detect the expression of various growth factor receptors on brain tumor cell lines which are going to be used in these studies. Materials and Methods : The authors detected transferrin receptor(TR), insulin-like growth factor-1 receptor(IGF-1R), and interleukin-4 receptor(IL-4R) on medulloblastoma cell line(Daoy) and glioblastoma cell lines(U373 MG and T98 G) by flow cytometric analysis. Results : TR was expressed on Daoy, U373 MG, and T98 G. IGF-1R was expressed on Daoy and U373 MG, but not on T98 G. IL-4R was expressed on all cell lines tested. Conclusion : The transferrin and interleukin-4 receptors might be good targets for immunotoxin therapy. The results should be considered in additional in vitro and in vivo studies regarding immunotoxin and in establishing the proper treatment model of the immunotoxin therapy including selection of the adequate immunotoxin.

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Serum and seminal plasma insulin-like growth factor-1 in male infertility

  • Lee, Hyo Serk;Park, Yong-Seog;Lee, Joong Shik;Seo, Ju Tae
    • Clinical and Experimental Reproductive Medicine
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    • v.43 no.2
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    • pp.97-101
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    • 2016
  • Objective: Growth hormone and its mediator, insulin-like growth factor-1 (IGF-1), have been suggested to exert gonadotropic actions in both humans and animals. The present study was conducted to assess the relationship between serum IGF-1 concentration, seminal plasma concentration, and sperm parameter abnormalities. Methods: A total of 79 men were enrolled in this study from December 2011 to July 2012 and were prospectively analyzed. Patient parameters analyzed included age, body mass index, smoking status, urological history, and fertility history. Patients were divided into four groups based on their semen parameters: normal (A, n=31), abnormal sperm motility (B, n=12), abnormal sperm morphology (C, n=20), and two or more abnormal parameters (D, n=16). Patient seminal plasma and serum IGF-1 concentrations were determined. Results: Patient baseline characteristics were not significantly different between any of the groups. The serum IGF-1 levels in groups B, C, and D were significantly lower than the levels in group A; however, the seminal plasma IGF-1 levels were not significantly different between any of the groups. Conclusion: Men with abnormal sperm parameters had significantly lower levels of serum IGF-1 compared with men with normal sperm parameters. Seminal plasma IGF-1 levels, however, did not differ significantly between the groups investigated here. Further investigations will be required to determine the exact mechanisms by which growth hormone and IGF-1 affect sperm quality.

Effect of Insulin-like Growth Factor-1 on Bone Morphogenetic Protein-2 Expression in Hepatic Carcinoma SMMC7721 Cells through the p38 MAPK Signaling Pathway

  • Xu, Guan-Jun;Cai, Sheng;Wu, Jian-Bing
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.4
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    • pp.1183-1186
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    • 2012
  • Objective: To observe the effect of insulin-like growth factor-1 (IGF-1) on bone morphogenetic protein (BMP)-2 expression in hepatocellular carcinoma SMMC7721 cells. Methods: Cells were divided into blank control, IGF-1, IGF-1 + SB203580, and SB203580 groups. SB203580 was used to block the p38 MAPK signaling pathway. Changes in the expression of BMP-2, p38 MAPK, and phosphorylated p38, MERK, ERK and JNK were determined using reverse transcription polymerase chain reactions (RT-PCR) and Western blot analysis. Results: Protein expression of phosphorylated BMP-2, MERK, ERK, and JNK was significantly up-regulated by IGF-1 compared with the control group ($1.138{\pm}0.065$ vs. $0.606{\pm}0.013$, $0.292{\pm}0.005$ vs. $0.150{\pm}0.081$, $0.378{\pm}0.006$ vs. $0.606{\pm}0.013$, and $0.299{\pm}0.015$ vs. $0.196{\pm}0.017$, respectively; P<0.05). Levels of BMP-2 and phosphorylated MERK and JNK were significantly reduced after blocking of the p38MAPK signaling pathway ($0.494{\pm}0.052$ vs. $0.165{\pm}0.017$, $0.073{\pm}0.07$ vs. $0.150{\pm}0.081$, and $0.018{\pm}0.008$ vs. $0.196{\pm}0.017$, respectively; P<0.05), but such a significant difference was not observed for phosphorylated ERK protein expression ($0.173{\pm}0.07$ vs. $0.150{\pm}0.081$, P>0.05). Conclusion: IGF-1 can up-regulate BMP-2 expression, and p38 MAPK signaling pathway blockage can noticeably reduce the up-regulated expression. We can conclude that the up-regulatory effect of IGF-1 on BMP-2 expression is realized through the p38 MAPK signaling pathway.

Insulin-like growth factor-1 improves diabetic cardiomyopathy through antioxidative and anti-inflammatory processes along with modulation of Akt/GSK-3β signaling in rats

  • Wang, Cheng Yu;Li, Xiang Dan;Hao, Zhi Hong;Xu, Dongyuan
    • The Korean Journal of Physiology and Pharmacology
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    • v.20 no.6
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    • pp.613-619
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    • 2016
  • Diabetic cardiomyopathy (DCM), a serious complication of diabetes mellitus, is associated with changes in myocardial structure and function. This study sought to explore the ability of insulin-like growth factor-1 (IGF-1) to modulate DCM and its related mechanisms. Twenty-four male Wistar rats were injected with streptozotocin (STZ, 60 mg/kg) to mimic diabetes mellitus. Myocardial fibrosis and apoptosis were evaluated by histopathologic analyses, and relevant proteins were analyzed by Western blotting. Inflammatory factors were assessed by ELISA. Markers of oxidative stress were tested by colorimetric analysis. Rats with DCM displayed decreased body weight, metabolic abnormalities, elevated apoptosis (as assessed by the bcl-2/bax ratio and TUNEL assays), increased fibrosis, increased markers of oxidative stress (MDA and SOD) and inflammatory factors (TNF-${\alpha}$ and IL-$1{\beta}$), and decreased phosphorylation of Akt and glycogen synthase kinase (GSK-$3{\beta}$). IGF-1 treatment, however, attenuated the metabolic abnormalities and myocardial apoptosis, interstitial fibrosis, oxidative stress and inflammation seen in diabetic rats, while also increasing the phosphorylation levels of Akt and GSK-$3{\beta}$. These findings suggest that IGF-1 ameliorates the pathophysiological progress of DCM along with an activation of the Akt/GSK-$3{\beta}$ signaling pathway. Our findings suggest that IGF-1 could be a potential therapeutic choice for controlling DCM.

Molecular Characterization and Expression Analysis of Insulin-like Growth Factor-1 and Insulin-like Growth Factor Binding Protein-1 Genes in Qinghai-Tibet Plateau Bos grunniens and Lowland Bos taurus

  • Chen, Ya-bing;Fu, Mei;Lan, Dao-liang;Li, Jian
    • Asian-Australasian Journal of Animal Sciences
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    • v.28 no.1
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    • pp.20-24
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    • 2015
  • Insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-1 (IGFBP-1) play a pivotal role in regulating cellular hypoxic response. In this study, we cloned and characterized the genes encoding IGF-1 and IGFBP-1 to improve the current knowledge on their roles in highland Bos grunniens (Yak). We also compared their expression levels in the liver and kidney tissues between yaks and lowland cattle. We obtained full-length 465 bp IGF-1 and 792 bp IGFBP-1, encoding 154 amino acids (AA) IGF-1, and 263 AA IGFBP-1 protein, respectively using reverse transcriptase-polyerase chain reaction (RT-PCR) technology. Analysis of their corresponding amino acid sequences showed a high identity between B. grunniens and lowland mammals. Moreover, the two genes were proved to be widely distributed in the examined tissues through expression pattern analysis. Real-time PCR results revealed that IGF-1 expression was higher in the liver and kidney tissues in B. grunniens than in Bos taurus (p<0.05). The IGFBP-1 gene was expressed at a higher level in the liver (p<0.05) of B. taurus than B. grunniens, but it has a similar expression level in the kidneys of the two species. These results indicated that upregulated IGF-1 and downregulated IGFBP-1 are associated with hypoxia adaptive response in B. grunniens.