• Title/Summary/Keyword: Insulin-like Growth Factor I

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Role of the Nuclear Transcription Factor NF-κB Caused by Acute Hypoxia in the Heart (급성 저산소증 상태에서 심장 내 전사인자 NF-κB의 기능)

  • Joo, Chan Uhng;Juhng, Woo Suk;Kim, Jae Cheol;Yi, Ho Keun
    • Clinical and Experimental Pediatrics
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    • v.45 no.9
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    • pp.1106-1113
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    • 2002
  • Purpose : Nuclear ($factor-{\kappa}BNF-{\kappa}B$) is now recognized as playing a potential role in programmed cell death and the adaptive response to various stress. Cellular hypoxia is a primary manifestation of many cardiovascular diseases. It seems that vascular endothelial growth factor (VEGF) and insulin like growth factor-I(IGF-I) have a function as a protective molecule in the heart against several stress including hypoxia. In this study, the role of $NF-{\kappa}B$ to the cellular response and regulation of protective molecules against the acute hypoxia in the heart was studied. Methods : To cause acute hypoxic stress to the heart, Sprague Dawley rats were exposed to hypoxic chamer($N_2$ 92% and $O_2$ 8%). After the hypoxic exposure, nuclear proteins, total proteins and mRNA were isolated from heart. Translocation of the transcription factors $NF-{\kappa}B$, NF-ATc, AP-1 and NKX-2.5 were evaluated by electrophoretic mobility shift assay(EMSA). The expression of IGF-I and VEGF were studied before and after the hypoxic stress by competitive-PCR, Northern hybridization and Western hybridization. To confirm the role of the $NF-{\kappa}B$ in the heart, the rats also were pretreated with diethyl-dithiocarbamic acid(DDTC) into peritoneal cavity to block $NF-{\kappa}B$ translocation into nucleus. Results : The expression of $NF-{\kappa}B$, AP-1 and NF-ATc were increased by the hypoxic stress. Increased expression of the VEGF and IGF-I were also observed by the hypoxic stress. However, the blocking of the $NF-{\kappa}B$ translocation reduced those expressions of VEGF and IGF-I. Conclusion : These results suggest that $NF-{\kappa}B$ has a protective role against the acute hypoxia through several gene expression, especially VEGF and IGF-I in heart muscle.

The Relationships between Plasma Insulin-like Growth Factor (IGF)-1 and IGF-Binding Proteins (IGFBPs) to Growth Pattern, and Characteristics of Plasma IGFBPs in Steers

  • Lee, H.G.;Hidari, H.;Kang, S.K.;Hong, Z.S.;Xu, C.X.;Kim, S.H.;Seo, K.S.;Yoon, D.H.;Choi, Y.J.
    • Asian-Australasian Journal of Animal Sciences
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    • v.18 no.11
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    • pp.1575-1581
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    • 2005
  • This study was conducted to determine the characteristics of IGFBPs in plasma of steers, and to profile the relationship between growth and plasma IGF-1 and IGFBPs with aging in Holstein steers. Four blots of IGFBP at molecular weights of 38-43, 34, 29-32 and 24 kDa bands were detected by western ligand blot assay using $^{125}I-IGF-1$. On the basis of immunoblotting with anti-bovine IGFBP-2 and -3 antiserums, we observed the band for IGFBP-2 at approximately 34 kDa, and the IGFBP-3 band was detected at 38-43 kDa and 34 kDa in adult steers and calves. The IGFBP-3 antiserum used on the blots exhibited significant cross-reactivity with 34 kDa IGFBP-2. Furthermore, the 38-43 kDa IGFBP-3 bands were reduced to a 36 kDa band after deglycosylation, whereas the 34 kDa IGFBP-2 was intact. The plasma IGF-1, IGFBP-3 and other IGFBPs showed stability throughout a whole day. The change in live weight was found to be positively correlated to the plasma IGF-1 concentration (r = 0.6801, n = 64, p<0.05) and plasma IGFBP-3 (r = 0.6321, n = 64, p<0.05), while inversely correlated to plasma IGFBP-2 (r = -0.2919, n = 64, p<0.05). Furthermore, plasma IGF-1 was positively correlated to plasma IGFBP-3 (r = 0.6191, p<0.001), but was not correlated to plasma IGFBP-2. The portion of IGFBP-2 for total IGFBPs in calves was higher than in adult steers (p<0.05) and was decreased with growth, whereas that of IGFBP-3 was increased with increased live weight (p<0.05). The ratio IGFBP-3 for IGFBP-2 (BP-3/BP-2) was increased with growing of liveweight. Therefore, the changes in plasma IGF-1 level with increased liveweight may be related to the changes in plasma IGFBP-3 level and IGFBP-2 may give an important role in anabolic action of IGF-1 with the growth of body during calfhood in Holstein steers.

Effect of Dietary Glycoprotein Extracted from Porphyra yezoensis on Growth Performance and Resistance against Edwardsiella tarda in Olive Flounder Paralichthys olivaceus Juveniles (김(Porphyra yezoensis)에서 추출한 당단백질의 사료내 첨가가 넙치(Paralichthys olivaceus) 치어 성장 및 Edwardsiella tarda 저항성에 미치는 영향)

  • Kim, Kang-Woong;Choi, Jeong-Wook;Kim, Kyoung-Duck;Han, Hyon-Sob;An, Cheul-Min;Lee, Bong-Joo;Choi, Youn Hee;Nam, Taek Jeong
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.45 no.6
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    • pp.606-611
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    • 2012
  • This study examined the effects of dietary glycoprotein extracted from Porphyra yezoensi on growth performance and resistance against the pathogenic bacteria Edwardsiella tarda in olive flounder. A porphyra-originated glycoprotein (P) was extracted using sequential processes of water and ethanol treatment. P extracts were added to a fish-meal-based diet at concentrations of 0.0, 0.5, and 1.0% (designated as Con, $P_{0.5}$, and $P_{1.0}$, respectively). Fish were fed one of the three experimental diets for 10 weeks. All fish groups exhibited over 96.7% survival during the experimental period. Results indicated that the fish fed diets containing P showed an increase in growth performance, including enhanced weight gain, specific growth rate, and feed efficiency. An increase in insulin-like growth factor (IGF-1) was observed in the fish fed the $P_{1.0}$ diet, as compared to those fed Con. At the end of the 10-week feeding trial, all fish were infected with E. tarda, and accumulated mortality was monitored for 8 days. Fish fed the Con diet exhibited increasing mortality from day 3 to the end of the challenge test, whereas the mortality of P-fed fish ceased at day 5. We suggest that supplementation with P-originated glycoprotein in aquafeed may increase growth performance and resistance against pathogenic bacteria in olive flounder juveniles.

Pretreatment Effects of Regular Aerobic Training on the IGF System and Hepatotoxicity Induced by Doxorubicin in Rats

  • Alishahi, Ailin;Roshan, Valiollah Dabidi;Hedayyati, Mehdi
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7427-7431
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    • 2013
  • Aims: To examine the pretreatment effects of regular aerobic training on the IGF system (IGF-I, IGFBP-3 and IGF/IGFBP) and doxorubicin(DOX) induced hepatotoxicity in rats. Materials and Methods: Forty-eight male rats were divided into groups:(1) control+placebo (2) $control+DOX_{10}mg{\cdot}kg^{-1}$ (3) $control+DOX_{20}mg{\cdot}kg^{-1}$ (4) training+placebo (5) $training+DOX_{10}mg{\cdot}kg^{-1}$ (6) $training+DOX_{20}mg{\cdot}kg^{-1}$. Hepatotoxicity was induced by DOX with dosages of 10 and 20 $mg{\cdot}kg^{-1}$. The rats in groups 4, 5 and 6 performed treadmill running of 25-54 min/day and 15-20 m/min, 5 days/wk for 6 wks. At the end of the aerobic training protocol, rats in the 1 and 4 groups, in the 2 and 5 groups and in the 3 and 6 groups received saline solution, $DOX_{10}mg{\cdot}kg^{-1}$ and $DOX_{20}mg{\cdot}kg^{-1}$, respectively. Results: Administration of $DOX_{20}mg{\cdot}kg^{-1}$ caused a significant increase in IGF-1 and IGF-1/IGFBP-3, an insignificant decrease in IGFBP-3, as compared to the control+placebo group. However, after six weeks of aerobic training and DOX treatment with $10mg{\cdot}kg^{-1}$ and or/ $20mg{\cdot}kg^{-1}$ an insignificant decrease in IGF-1, an insignificant increase in IGFBP-3 and a significant decrease in IGF-1/IGFBP-3 were detected, in comparison to $C+DOX_{10}$ and $C+DOX_{20}$. Conclusions: Hepatotoxicity of doxorubicin is dose-dependent and pretreatment with regular aerobic training may improve DOX-induced hepatotoxicity by up-regulation of IGFBP3.

Ginsenoside Rg1 enhances the healing of injured tendon in achilles tendinitis through the activation of IGF1R signaling mediated by oestrogen receptor

  • Wu, Tianyi;Qi, Wenxiao;Shan, Haojie;Tu, Bin;Jiang, Shilin;Lu, Ye;Wang, Feng
    • Journal of Ginseng Research
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    • v.46 no.4
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    • pp.526-535
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    • 2022
  • Background: During the pathogenesis of tendinopathy, the chronic inflammation caused by the injury and apoptosis leads to the generation of scars. Ginsenoside Rg1 (Rg1) is extracted from ginseng and has anti-inflammatory effects. Rg1 is a unique phytoestrogen that can activate the estrogen response element. This research aimed to explore whether Rg1 can function in the process of tendon repair through the estrogen receptor. Methods: In this research, the effects of Rg1 were evaluated in tenocytes and in a rat model of Achilles tendinitis (AT). Protein levels were shown by western blotting. qRT-PCR was employed for evaluating mRNA levels. Cell proliferation was evaluated through EdU assay and cell migration was evaluated by transwell assay and scratch test assay. Results: Rg1 up-regulated the expression of matrix-related factors and function of tendon in AT rat model. Rg1 reduced early inflammatory response and apoptosis in the tendon tissue of AT rat model. Rg1 promoted tenocyte migration and proliferation. The effects of Rg1 on tenocytes were inhibited by ICI182780. Rg1 activates the insulin-like growth factor-I receptor (IGF1R) and MAPK signaling pathway. Conclusion: Rg1 promotes injured tendon healing in AT rat model through IGF1R and MAPK signaling pathway activation.

Growth responses to growth hormone therapy in children with attenuated growth who showed normal growth hormone response to stimulation tests (성장호르몬 자극검사가 정상인 성장 장애 소아 환자에게서 성장호르몬 투여에 따른 성장속도의 변화)

  • Kim, Jae-Hyun;Chung, Hye-Rim;Lee, Young-Ah;Lee, Sun-Hee;Kim, Ji-Hyun;Shin, Choong-Ho;Yang, Sei-Won
    • Clinical and Experimental Pediatrics
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    • v.52 no.8
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    • pp.922-929
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    • 2009
  • Purpose : The aim was to investigate the clinical characteristics and responses to growth hormone (GH) therapy in children with attenuated growth who showed normal GH responses to GH stimulation tests (GHST). Methods : The study included 39 patients with height velocity (HV) of less than 4 cm/yr and normal GHST results. Clinical characteristics of patients were analyzed retrospectively. Results : Eleven were born as small for gestational age (SGA) and 28 as appropriate for age (AGA). In the SGA group, the standard deviation score (SDS) of age and height measured at their first visit was significantly low. Sixteen patients were treated with GH and six of 23 without GH therapy were followed for 1 year after GHST. The mean (range) of HV was 7.7 (4.9 to 11.1) cm/yr in patients with GH therapy and 3.7 (2.7 to 4.5) cm/yr in those without GH therapy, which was statistically significant (P<0.001). In the GH-treated group, HV and difference in height SDS during the treatment increased significantly (P<0.001; P< 0.001, respectively). HV increased after 1 year of GH therapy in the SGA and AGA groups (SGA, P=0.043; AGA, P=0.003). The level of Insulin-like growth factor-I was significantly lower in GH-treated patients with height SDS <-3 than those with ${\geq}3$ (P=0.023). Conclusion : In children with growth failure and normal GHST, HV increases significantly by short-term GH therapy. The assessment of long-term effects of GH therapy is necessary. Moreover, further studies should be considered to evaluate the GH-IGF-I axis due to the possibility of GH insensitivity syndrome.

Effects of Castration on Androgen Receptor, IGF-I Ea, MGF and Myostatin Gene Expression in Skeletal Muscles of Male Pigs

  • Yao, Yuchang;Cai, Zhaowei;Zhang, Lifan;Zhao, Chunjiang;Wu, Keliang;Xu, Ningying;Liu, Gang;Wu, Changxin
    • Asian-Australasian Journal of Animal Sciences
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    • v.22 no.8
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    • pp.1069-1077
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    • 2009
  • Castration of male pig produces significant negative effects on skeletal muscle development. The androgen receptor (AR), two splice variants of insulin-like growth factor-I (IGF-I Ea and MGF) and the myostatin gene may play important roles in this process. In the present study, the expression of AR, IGF-I Ea, MGF and myostatin genes in three skeletal muscles, the brachialis, longissimus and semitendinosus, were studied using real-time quantitative RT-PCR. Our experimental design used 14 pairs of male Landrace sire${\times}$Yorkshire dam piglets. The two piglets in each pair were full sibs, one of which was castrated at 21 d of age; the other remained intact. The study group was divided into subgroups of equal size. Animals in the first subgroup were slaughtered at 147 d and those of the second at 210 d of age. Carcass weight and lean meat yield were similar between boars and barrows at 147 d of age (p>0.05), whereas barrows had lower carcass weight and less lean meat yield at 210 d of age (p<0.05). Castration caused down-regulation of AR gene expression at both 147 and 210 d of age (p<0.05). The two splice variants of the IGF-I gene from porcine skeletal muscle were cloned using RT-PCR, and it was found that MGF differs from IGF-I Ea in having a 52-base insert in the last coding exon of the mRNA. Both splice variants were down-regulated by castration only at 210 d of age (p<0.05). No differences in expression of the myostatin gene were observed between boars and barrows at either 147 or 210 d of age (p>0.05). These results suggest that the downregulation of AR, IGF-I Ea and MGF gene expression following castration helps to explain the negative effect of castration on skeletal muscle development.

The Effects of Treadmill Exercise on Inhibition of Soleus Muscle Atrophy and Improvement Functional Recovery after Spinal Cord Contusion in the Rats (척수타박손상 후 트레드밀운동이 근 위축지연과 기능적 회복에 미치는 효과)

  • Oh, Myung-Jin;Jang, Moon-Nyeo;Seo, Tae-Beom;Kim, Jong-Oh;Byun, Jae-Jong;Yoon, Jin-Hwan;Jeong, Il-Gyu
    • Journal of Life Science
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    • v.19 no.11
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    • pp.1651-1657
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    • 2009
  • Physical activity and exercise can promote sensorimotor recovery from central nerve injury. It has been suggested that the functional recovery promoted by exercise training after spinal cord injury might be associated with insulin-like growth factor-I in the inflicted muscle. To investigate morphological and biochemical change of the soleus muscle after spinal cord injury, all tissues were used for H&E, immunofluorescence staining and Western blot. Also, BBB-test was used to evaluate behavioral improvement after spinal cord contusion. Thirty male Sprague-Dawley rats ($230{\pm}10\;g$; 7week in age) were assigned equally to three different groups; Normal (n=10), SCI (n=10), SCI+TMT (n=10). Every rat in SCI and SCI+TMT groups underwent laminectomy at T9 level and then contusion on the exposed spinal cord site in anesthetized condition. After one week-recovery from contusion, every rat in the SCI+TMT group exercised on a motorized treadmill for 30min/d, 5d/wk for 7wks. TMT followed by injury increased IGF-I induction levels in the soleus muscle and inhibited muscle atrophy. Behavioral scales for 4 and 8 weeks after spinal cord injury were improved in the SCI+TMT group compared to the SCI group. These results suggest that treadmill exercise after spinal cord injury might promote functional recovery along with muscle regrowth through the up-regulation of IGF-1 in muscle tissue.

Effects of different levels of dietary crude protein on growth performance, blood profiles, diarrhea incidence, nutrient digestibility, and odor emission in weaning pigs

  • Hongjun Kim;Haewon Shin;Yoo Yong Kim
    • Animal Bioscience
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    • v.36 no.8
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    • pp.1228-1240
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    • 2023
  • Objective: This experiment was conducted to evaluate the effects of different levels of dietary crude protein (CP) on growth performance, blood profiles, diarrhea incidence, nutrient digestibility, and odor emission in weaning pigs. Methods: A total of 240 weaning ([Yorkshire×Landrace]×Duroc) pigs (8.25±0.050 kg body weight [BW]) were assigned to six treatments based on sex and initial BW, with five replicates of eight pigs per pen in a randomized complete block design. Experimental diets with different crude protein levels for early and late weaning phases were as follows: i) CP16, corn-soybean-based diet containing 16%/15% CP; ii) CP17, corn-soybean-based diet containing 17%/16% CP; iii) CP18, corn-soybean-based diet containing 18%/17% CP; iv) CP19, corn-soybean-based diet containing 19%/18% CP; v) CP20, corn-soybean-based diet containing 20%/19% CP; and vi) CP21, corn-soybean-based diet containing 21%/20% CP. Results: In the early weaning period, average daily feed intake increased when the dietary CP level decreased (linear, p<0.05). During the entire experimental period, average daily gain and the gain to feed ratio decreased when the dietary CP level increased (linear, p<0.01). Additionally, a decrease in dietary CP level resulted in a linear increase in final BW (linear, p<0.05). In the early and late weaning periods, blood urea nitrogen (BUN) decreased when the dietary CP level decreased (linear, p<0.01). There were no significant differences in creatinine, glucose, total protein, triglyceride or insulin-like factor-1 levels over the experimental period. The concentrations of immunoglobulin A (IgA) and IgG were not significantly affected by dietary CP levels during the experimental period. In the early weaning period, fecal and urine N decreased when the dietary CP level decreased (linear, p<0.01). No differences in nutrient digestibility among the treatments during the early weaning period were found. Throughout the whole experimental period, when the dietary CP level decreased in the weaning pig diet, the diarrhea incidence decreased linearly (linear, p<0.01). Throughout the whole experimental period, when the dietary CP level decreased in the weaning pig diet, ammonia, amines and hydrogen sulfide decreased linearly (linear, p<0.01). Conclusion: Reducing dietary CP could decrease diarrhea incidence, the concentration of BUN in serum and odor emission in manure. Furthermore, it could improve N excretion in feces and urine and growth performance in weaning pigs.

Ginsenoside Rg1 activates ligand-independent estrogenic effects via rapid estrogen receptor signaling pathway

  • Gao, Quan-Gui;Zhou, Li-Ping;Lee, Vien Hoi-Yi;Chan, Hoi-Yi;Man, Cornelia Wing-Yin;Wong, Man-Sau
    • Journal of Ginseng Research
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    • v.43 no.4
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    • pp.527-538
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    • 2019
  • Background: Ginsenoside Rg1 was shown to exert ligand-independent activation of estrogen receptor (ER) via mitogen-activated protein kinase-mediated pathway. Our study aimed to delineate the mechanisms by which Rg1 activates the rapid ER signaling pathways. Methods: ER-positive human breast cancer MCF-7 cells and ER-negative human embryonic kidney HEK293 cells were treated with Rg1 ($10^{-12}M$, $10^{-8}M$), $17{\beta}$-estradiol ($10^{-8}M$), or vehicle. Immunoprecipitation was conducted to investigate the interactions between signaling protein and ER in MCF-7 cells. To determine the roles of these signaling proteins in the actions of Rg1, small interfering RNA or their inhibitors were applied. Results: Rg1 rapidly induced $ER{\alpha}$ translocation to plasma membrane via caveolin-1 and the formation of signaling complex involving linker protein (Shc), insulin-like growth factor-I receptor, modulator of nongenomic activity of ER (MNAR), $ER{\alpha}$, and cellular nonreceptor tyrosine kinase (c-Src) in MCF-7 cells. The induction of extracellular signal-regulated protein kinase and mitogen-activated protein kinase kinase (MEK) phosphorylation in MCF-7 cells by Rg1 was suppressed by cotreatment with small interfering RNA against these signaling proteins. The stimulatory effects of Rg1 on MEK phosphorylation in these cells were suppressed by both PP2 (Src kinase inhibitor) and AG1478 [epidermal growth factor receptor (EGFR) inhibitor]. In addition, Rg1-induced estrogenic activities, EGFR and MEK phosphorylation in MCF-7 cells were abolished by cotreatment with G15 (G protein-coupled estrogen receptor-1 antagonist). The increase in intracellular cyclic AMP accumulation, but not Ca mobilization, in MCF-7 cells by Rg1 could be abolished by G15. Conclusion: Ginsenoside Rg1 exerted estrogenic actions by rapidly inducing the formation of ER containing signalosome in MCF-7 cells. Additionally, Rg1 could activate EGFR and c-Src ER-independently and exert estrogenic effects via rapid activation of membrane-associated ER and G protein-coupled estrogen receptor.