• Title/Summary/Keyword: IGF-I

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Signal Transduction of the Protective Effect of Insulin Like Growth Factor-1 on Adriamycin-Induced Apoptosis in Cardiac Muscle Cells

  • Chae, Han-Jung;Kim, Hyung-Ryong;Bae, Jee-hyeon;Chae, Soo-Uk;Ha, Ki-Chan;Chae, Soo-Wan
    • Archives of Pharmacal Research
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    • v.27 no.3
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    • pp.324-333
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    • 2004
  • To determine whether Insulin-like growth factor (IGF-I) treatment represents a potential means of enhancing the survival of cardiac muscle cells from adriamycin (ADR)-induced cell death, the present study examined the ability of IGF-I to prevent cell death. The study was performed utilising the embryonic, rat, cardiac muscle cell line, H9C2. Incubating cardiac muscle cells in the presence of adriamycin increased cell death, as determined by MTT assay and annexin V-positive cell number. The addition of 100 ng/mL IGF-I, in the presence of adriamycin, decreased apoptosis. The effect of IGF-I on phosphorylation of PI, a substrate of phosphatidylinositol 3-kinase (PI 3-kinase) or protein kinase B (AKT), was also examined in H9C2 cardiac muscle cells. IGF-I increased the phosphorylation of ERK 1 and 2 and $PKC{\;}{\zeta}{\;}kinase$. The use of inhibitors of PI 3-kinase (LY 294002), in the cell death assay, demonstrated partial abrogation of the protective effect of IGF-I. The MEK1 inhibitor-PD098059 and the PKC inhibitor-chelerythrine exhibited no effect on IGF-1-induced cell protection. In the regulatory subunit of PI3K-p85- dominant, negative plasmid-transfected cells, the IGF-1-induced protective effect was reversed. This data demonstrates that IGF-I protects cardiac muscle cells from ADR-induced cell death. Although IGF-I activates several signaling pathways that contribute to its protective effect in other cell types, only activation of PI 3-kinase contributes to this effect in H9C2 cardiac muscle cells.

Serum Levels of Insulin-Like Growth Factor-I in Flounder, Parlichthys olivaceus (넙치 (Parlichthys olivaceus) 혈액중 Insulin-like growth factor-I의 함유수준)

  • NAM Taek-Jeong;PARK Kie-Young;LEE Young-Don;KIM Yong-Uk
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.29 no.2
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    • pp.150-156
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    • 1996
  • Insulin-like growth factor-1 (IGF-I) is a mitogenic peptide with molecular mass of 7kDa. It is produced mainly in the liver and has important functions in the regulation of development and somatic growth. Recently, several investigations were undertaken to examine the biological actions and structures of IGF-I in fish. In this study, the serum levels of IGF-I were estimated from flounder, Parlichthys oilvaceus, before, during and after fasting, and the levels were accounted for 47 ng/ml, 40 ng/ml and 45 ng/ml, respectively. These results suggest that food deprivation primarily reduces IGF-I level in the blood.

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Role of cAMP, EGF, IGF-I and Protein Phosphorylation in Mammary Development II. Interaction Effects of EGF, IGF-I and Photoreactive Cyclic AMP on DNA Synthesis and Protein Phosphorylation (유선발달에 있어서 cAMP, EGF, IGF-I 및 단백질 인산화 작용의 역할 II. EGF, IGF-I 및 Photoreactive Cyclic AMP의 상호작용과 단백질 인산화 작용)

  • 여인서
    • Korean Journal of Animal Reproduction
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    • v.19 no.2
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    • pp.95-104
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    • 1995
  • Mouse mammary epithelial cells(NMuMG) were maintained onto 6-well plates (3$\times$105 cells/well) or chambered slide (1$\times$104 cells/well), in DMEM supplemented with 10% fetal calf serum. After serum starvation for 24 hours, DMNB (1$\mu$M) was added and exposed to UV light (300nm, 3 second pulse) after 2 hours from DMNB addition in order to activate DMNB which induces a rapid transient increase in intracellular cAMP upon UV irradiation. EGF (100ng/ml) and/or IGF-I (10ng/ml) were treated at the time of UV irradiation. Nuclear labeling index was estimated as percent of nuclear labeled cells(percent of S phase of cells) by incorporation of 3H-thymidine into DNA(1 hour pulse with 1$\mu$Ci/ml). DMNB(1$\mu$M), EGF (100ng/ml) and/or IGF-I (10ng/ml) signifciantly increased nuclear labeling index than those of control (P<0.05). Addition of DMNB+EGF or DMNB+EGF+IGF-I showed the interaction effect in nuclear labeling index (P<0.05). Protein kinase A activities by addition of EGF, IGF-I or EGF+IGF-I were 10.5, 9.8 or 9.4 unit/mg protein, respectively, and no statistical difference was found in comparison with control (P>0.05). Additon of DMNB+EGF showed the moderate interaction effect on tyrosyl kinase activity (P<0.1). In the fluorography analysis, there were no specific protein phosphorylation patterns were found at 1 or 15 minute by addition of DMNB. EGF and/or IGF-I. These results suggest that the interaction effect in nuclear labeling index by addition DMNB and EGF could be mediated through the modulation of tyrosyl kinase activity by cAMP.

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Effects of forskolin on secretion of insulin like growth factor-I in the perfused rat liver model (백서 간 관류모델에서 forskolin이 Insulin like growth factor-I의 분비에 미치는 효과)

  • Kang, Chang-won;Lee, Dae-yeol;Lee, Ho-il
    • Korean Journal of Veterinary Research
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    • v.39 no.5
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    • pp.938-944
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    • 1999
  • The insulin-like growth factor-I(IGF-I) is an important metabolic factor involved in cell growth and metabolism. Although secretion of IGF-I in rat liver is regulated by growth hormone, the effects of forskolin, adenylate cyclase activator, on secretion of IGF-I have not been reported. Therefore, a modified perfused rat liver model was used to investigate the regulatory effects of forskolin on IGF-I secretion in this experiment. The results were summerized as follows : 1. Modified perfused rat liver model was not changed to aspartate aminotransferase(AST), alanine aminotransferase(ALT) and lactic dehydrogenase(LDH) secretion in time. 2. The IGF-I secretion in hepatic cell was increased by forskolin($10^{-5}$, $10^{-6}$ and $10^{-7}M$) in a dose-dependent manner as compared with those of the controls, and significantly increased by $10^{-5}$ and $10^{-6}$ forskolin(p < 0.05). 3. Secretion of glucose in hepatic cell significantly was decreased by $10^{-5}$ forskolin as compared with those of controls(p < 0.05). These results suggest that forskolin may be involved in the regulation of IGF-I secretion in the perfused rat liver.

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Correlation of Cord Serum Adiponectin and IGF-I with Fetal Growth in Healthy Term Neonates (제대혈 Adiponectin과 IGF-I이 태아성장에 미치는 영향)

  • Kim, Ji-Young;Cho, Su-Jin;Kim, Hae-Soon;Park, Hye-Sook;Park, Eun-Ae
    • Neonatal Medicine
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    • v.15 no.1
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    • pp.38-43
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    • 2008
  • Purpose : The purpose of this study was to evaluate the relationship between cord serum adiponectin (APN) and IGF-I concentrations and fetal growth. Methods : Umbilical cord serum APN and IGF-I concentrations were measured in healthy term singleton deliveries (n=72). The association of cord serum APN and IGF-I concentrations was evaluated in relation to birth weight, height, head circumference, gender, ponderal index, placental weight, feto-placental (F/P) weight ratio, maternal weight gain, and maternal body mass index (BMI). Results : The mean cord serum APN was 29.2${\pm}$10.46 $\mu$g/mL. The cord serum APN and birth weight demonstrated a bell-shape relationship. The cord serum APN concentration was higher in females than males (P=0.001). The cord serum APN was negatively correlated with maternal BMI (r=-0.301, P=0.027), but the mean cord serum APN concentration was not correlated with birth height, birth head circumference, ponderal index, placental weight, F/P ratio, or maternal weight gain. The mean cord serum concentrations of IGF-I was 51.26${\pm}$21.54 ng/mL. The cord serum IGF-I concentration was positively correlated with birth weight (r=0.312, P=0.009), but not birth height, ponderal index, placental weight, F/P weight ratio, or maternal BMI. Conclusion : APN demonstrated a bell-shaped relationship with birth weight in healthy term infants. IGF-I was highly correlated with fetal growth, especially birth weight.

Evaluation of Serum Insulin-Like Growth Factor(IGF)-I, Insulin-Like Growth Factor Binding Protein(IGFBP)-2 and IGFBP-3 Levels in Healthy Korean Children (정상 어린이에서 혈청 인슐린양 성장인자-I과 인슐린양 성장인자 결합단백-2 및 -3의 농도 분석)

  • Yang, Gi Hoon;Jung, Hye Lim;Kim, Deok Soo;Shim, Jae Won;Shim, Jung Yeon;Park, Moon Soo
    • Clinical and Experimental Pediatrics
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    • v.48 no.3
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    • pp.298-305
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    • 2005
  • Purpose : We performed this study to evaluate the mean serum levels of insulin-like growth factor (IGF)-I, insulin-like growth factor binding protein(IGFBP)-2 and IGFBP-3 in healthy Korean children according to age and sex. Methods : Ninety two healthy children, consisting of 42 boys and 50 girls, were classified into five groups according to age : neonate; infancy; early childhood; late childhood; and adolescence. We measured serum levels of IGF-I, IGFBP-2 and IGFBP-3 by enzyme-linked immunosorbent assay(ELISA) and analysed the serum levels according to sex and age group. Results : For boys, the mean serum levels of IGF-I(ng/mL) in neonate, infancy, early childhood, late childhood and adolescence were $41.1{\pm}3.6$, $70.9{\pm}33.7$, $103.5{\pm}97.2$, $89.8{\pm}46.5$ and $51.4{\pm}27.8$, respectively. Those of IGFBP-2(ng/mL) were $8.2{\pm}3.4$, $5.8{\pm}0.4$, $9.3{\pm}4.0$, $9.5{\pm}1.1$ and $7.0{\pm}0.5$, respectively. Those of IGFBP-3(ng/mL) were $559.2{\pm}215.2$, $1,333.3{\pm}692.5$, $2,254.6{\pm}1,513.8$, $2,447.1{\pm}1,464.2$, $1,533.6{\pm}807.4$, respectively. For girls, the mean serum levels of IGF-I(ng/mL) according to five age groups were $53.3{\pm}9.5$, $99.3{\pm}45.8$, $69.6{\pm}51.1$, $106.2{\pm}67.0$ and $145.1{\pm}127.8$, respectively. Those of IGFBP-2 (ng/mL) were $9.1{\pm}7.4$, $5.3{\pm}0.9$, $6.9{\pm}2.0$, $10.5{\pm}3.0$ and $7.9{\pm}1.3$, respectively. Those of IGFBP-3(ng/mL) were $858.2{\pm}433.4$, $1,834.8{\pm}851.3$, $1,404.3{\pm}570.2$, $2,203.5{\pm}899.4$ and $2,029.3{\pm}1,316.7$, respectively. There were significant positive correlations observed between IGF-I and IGFBP-3 levels(r=0.589, P=0.000). Conclusion : IGF-I and IGFBP-3 levels increased as children get older. The peak level of IGFBP-3 was observed in late childhood for both boys and girls, suggesting a current trend of children reaching peak growth velocity before adolescence. The IGFBP-2 level was higher in neonates compare to infancy, suggesting that IGFBP-2 is an important substance for fetal growth.

The Effect of Estrogen on the Transcription of the Insulin-like Growth Factor-I Gene in the Uterus (자궁 내 insulin-like growth factor-I 유전자 발현에 미치는 에스트로겐의 영향)

  • Kwak, In-Seok
    • Journal of Life Science
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    • v.19 no.5
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    • pp.593-597
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    • 2009
  • The uterus plays a critical role in pregnancy and steroid hormones, and both estrogen (E2) and progesterone (P4) especially play important roles in the cross-talk between embryos and uterus to support the pregnancy. E2 stimulates uterine growth during early pregnancy to prepare for implantation of embryos. This cross-talk during the implantation period involves hormones (E2 and P4) and growth factors, including insulin-like growth factor-I (IGF-I). In the uterus of a pregnant pig, the action of E2 is mediated by estrogen receptor-${\beta}$ (ER-${\beta}$). The expression of ER-a was much higher in early pregnancy than in mid- and late- pregnancy, suggesting E2 secretion from embryos enhances transcription of ER-a during early pregnancy. In order to prove whether IGF-I is an E2 target gene, quantitative real-time PCR was performed on ovariectomized murine uterus with E2 and/or P4 treatment(s). Increased IGF-I mRNA expression was observed with E2 treatment, however, it was not significantly induced by P4 treatment, which clearly demonstrates that, in mice, E2 depends on the activation of uterine IGF-I gene expression. The expression of IGF-I in the uterus of pigs was much higher in early pregnancy than in mid- and late- pregnancy and these data exhibited the same expression pattern with the ER-${\beta}$ gene expression in the uterus. It suggests that a positive co-relationship between IGF-I and ER-${\beta}$ expression exists in the uterus, and that both gene expressions of IGF-I and ER-${\beta}$ are regulated by E2. It further suggests that uterine the IGF-I gene expression might be initiated by E2 secreted from embryos to increase ER-${\beta}$ gene expression, and that this increased ER-${\beta}$ further stimulates the expression of IGF-I in the uterus during early pregnancy.

Effects of Carassius carassius Hot-Water Extracts on Serum Insulin-like Growth Factor-I(IGF-I) and IGF-Binding Proteins in Rats (붕어육의 단백질 열수추출물이 흰쥐의 혈청중 Insulin-like Growth Factor-I(IGF-I)과 IGF-Binding Proteins에 미치는 영향)

  • 남택정;권미진;류홍수;김경숙;변재형
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.28 no.3
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    • pp.685-690
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    • 1999
  • The insulin like growth factors(IGFs) are bound to several binding proteins(IGFBPs) that appear to regulate IGF transfort, receptor binding, and its action. The concentrations of these peptides are regulated by quantity and nutritional quality of dietary proteins. The aim of this study was to compare the effects of two diets, which differed in their protein source, Carassius carassius(CC), Carassius carassius hot water extract(CCHE), for 4 weeks. Body weight was significantly increased in the CC group(74.14$\pm$12.00 to 266.31$\pm$36.62g; p<0.01). Likewise, IGF I concentration of CC group(101.76$\pm$15.90 ng/ml) was significantly higher than that of CCHE group(38.50$\pm$ 11.20ng/ml; p<0.05). By western immunoblot analysis, especially IGFBP 1, 2 levels are increased, whereas IGFBP 3 level was de creased in CCHE group. After extraction of browning material from each samples, the extractive was filtered and absorbance at 420nm was measured. The absorbance of CCHE group was significantly higher than that of CC group. These results suggest that IGF I can be employed as an index of protein metabolism, particulary as a simple index in the assessing the status of protein nutrition.

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Effects of Volatile Fatty Acids on IGF-I, IGFBP-3, GH, Insulin and Glucagon in Plasma, and IGF-I and IGFBP-3 in Different Tissues of Growing Sheep Nourished by Total Intragastric Infusions

  • Zhao, Guang-Yong;Sun, Ya-Bo
    • Asian-Australasian Journal of Animal Sciences
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    • v.23 no.3
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    • pp.366-371
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    • 2010
  • Twelve Suffolk${\times}$Small-tail-Han male sheep (body weight 21-26 kg), aged four months, were used to study the effects of volatile fatty acids (VFA) on IGF-I (insulin-like growth factor-I), IGFBP-3 (insulin-like growth factor binding protein-3), GH (growth hormone), insulin and glucagon in plasma, and IGF-I and IGFBP-3 in different tissues. The sheep were randomly divided into four groups with 3 sheep in each group. The sheep were sustained by total intragastric infusions and four levels of mixed VFA (the molar proportion of acetic acid, propionic acid and butyric acid was 65:25:10), which supplied 333, 378, 423 and 468 KJ energy/kg $W^{0.75}$/d, were infused into the rumen as experimental Treatments I, II, III and IV, respectively. The experiment lasted 12 days, of which the first 8 days were for pretreatment and the last 4 days for collection of samples. At the end of the experiment, blood samples were taken and then the sheep were slaughtered and tissue samples from the rumen ventral sac, rumen dorsal sac, liver, duodenum and Longissimus dorsi muscle were obtained. IGF-I, IGFBP-3, GH, insulin and glucagon in plasma and IGF-I and IGFBP-3 in different tissues were analysed. Results showed that the concentration of IGF-I, IGFBP-3, GH, insulin or glucagon in plasma and the content of IGF-I and IGFBP-3 in the rumen dorsal sac, rumen ventral sac, liver or Longissimus dorsi muscle were increased with VFA infusion level (p<0.05). No significant differences were found in duodenum IGF-I between Treatments I and II and in rumen dorsal sac IGFBP-3 between Treatments II and III (p>0.05). It was concluded that IGF-I, IGFBP-3, GH, insulin and glucagon in plasma and IGF-I and IGFBP-3 in rumen dorsal sac, rumen ventral sac, liver and Longissimus dorsi muscle were increased significantly with increasing level of ruminal infusion of mixed VFA.

Effects of Insulin-like Growth Factor in Peritoneal Fluid of Patients with Endometriosis on the Proliferation of Endometrial Stromal Cells (자궁내막증 환자의 복강액내 IGF가 자궁내막 기질세포 증식에 미치는 영향)

  • Kim, Jung-Gu;Suh, Chang-Seok;Kim, Seok-Hyun;Choi, Young-Min;Moon, Shin-Yong;Lee, Jin-Yong
    • Clinical and Experimental Reproductive Medicine
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    • v.26 no.3
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    • pp.331-338
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    • 1999
  • The purposes of this study were to evaluate the effects of insulin-like growth factor (IGF)s in peritoneal fluid (PF) from patients with and without endometriosis on the proliferation of endometrial stromal cells and to investigate the effects of type I IGF receptor antibody on the response of endometrial stromal cells to PF from patients with endometriosis. IGFs in PF from patients with endometriosis (n=14) and without endometriosis (n=10) were measured by immunoradiometric assay and PF samples were divided into low IGF-I PF group (less than 85 ng/ml) and high IGF-I PF group (more than 85 ng/ml). Endometrial stromal cells from patients without endometriosis were cultured in serum free media in the presence or absence of 1 % PF and thymidine incorporation test were used to evaluate the proliferation of endometrial stromal cells. Also cultures were incubated with type I IGF receptor monoclonal antibody (${\alpha}IR_3$) before adding PF. PF from patients with endometriosis and without endometriosis increased thymidine incorporation in endometrial stromal cells. In patients with endometriosis, high IGF-I PF group had high IGF-II levels and resulted in higher thymidine incorporation than low IGF-I PF group but no significant difference in increase in thymidine incorporation between high IGF-I and low IGF-I PF group was noted in patients without endometriosis. There was not a significant correlation between increase in thymidine incorporation and IGF-I levels in PF from patients without endometriosis but in PF from patients with endometriosis. Preincubation with ${\alpha}IR_3$ significantly inhibited the mitogenic response of endometrial stromal cells to PF. Our data indicate that IGF-I in PF may be involved in the growth of ectopic endometrium in patients with endometriosis.

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