• Title/Summary/Keyword: FoxM1

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The effects of long term endurance or resistance exercise training on anabolic and catabolic pathway in skeletal muscle of middle-aged rats (장기간의 지구성 운동 또는 저항성 운동이 중년 흰쥐의 골격근 내 단백질 동화 및 이화기전에 미치는 영향)

  • Jung, Su-Ryun;Kim, Ki-Jin;Kho, Jin-Ho
    • 한국체육학회지인문사회과학편
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    • v.55 no.6
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    • pp.691-700
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    • 2016
  • The purpose of this study was to investigate the effects of long-term endurance exercise or resistance exercise training on muscle anabolic/catabolic pathway. 50wks-old male Wistar rats(n=30) were randomly assigned for 3 groups (sedentary, endurance exercise, resistance exercise group). After 12-week of training, plantaris muscles were dissect to measure protein level. Akt/mTOR signal-related proteins were significantly increased only after resistance exercise training, but catabolic signal-related proteins, FoxO1 and MuRF1, were significantly decreased after resistance and endurance exercise training. After endurance exercise training, AMPK and PGC-1α protein levels were significantly increased. Therefore, the endurance exercise training has been shown to affect the protein balance of aging muscle through inhibition of muscle protein catabolism. The present results suggest the possibility that not only resistance exercise but also endurance exercise will be affectable to keep or increase muscle volume and capacity of middle-aged people.

Inhibition of melanogenesis by sodium 2-mercaptoethanesulfonate

  • Kim, Jeong-Hwan;Oh, Chang-Taek;Kwon, Tae-Rin;Kim, Jong Hwan;Bak, Dong-Ho;Kim, Hyuk;Park, Won-Seok;Kim, Beom Joon
    • The Korean Journal of Physiology and Pharmacology
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    • v.24 no.2
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    • pp.149-156
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    • 2020
  • Sodium 2-mercaptoethanesulfonate (mesna) is a protective agent that is widely used in medicine because of its antioxidant effects. Recently, reactive oxygen species (ROS) were shown to increase pigmentation. Thus, ROS scavengers and inhibitors of ROS production may suppress melanogenesis. Forkhead box-O3a (FoxO3a) is an antimelanogenic factor that mediates ROS-induced skin pigmentation. In this study, we aimed to investigate the whitening effect of mesna and the signaling mechanism mediating this effect. Human melanoma (MNT-1) cells were used in this study. mRNA and protein expression were measured by real-time quantitative PCR and Western blotting analysis to track changes in FoxO3a-related signals induced by mesna. An immunofluorescence assay was performed to determine the nuclear translocation of FoxO3a. When MNT-1 melanoma cells were treated with mesna, melanin production and secretion decreased. These effects were accompanied by increases in FoxO3a activation and nuclear translocation, resulting in downregulation of four master genes of melanogenesis: MITF, TYR, TRP1, and TRP2. We found that mesna, an antioxidant and radical scavenger, suppresses melanin production and may therefore be a useful agent for the clinical treatment of hyperpigmentation disorders.

A Mixture of Morus alba and Angelica keiskei Leaf Extracts Improves Muscle Atrophy by Activating the PI3K/Akt/mTOR Signaling Pathway and Inhibiting FoxO3a In Vitro and In Vivo

  • Hyun Hwangbo;Min Yeong Kim;Seon Yeong Ji;Da Hye Kim;Beom Su Park;Seong Un Jeong;Jae Hyun Yoon;Tae Hee Kim;Gi-Young Kim;Yung Hyun Choi
    • Journal of Microbiology and Biotechnology
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    • v.33 no.12
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    • pp.1635-1647
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    • 2023
  • Muscle atrophy, which is defined as a decrease in muscle mass and strength, is caused by an imbalance between the anabolism and catabolism of muscle proteins. Thus, modulating the homeostasis between muscle protein synthesis and degradation represents an efficient treatment approach for this condition. In the present study, the protective effects against muscle atrophy of ethanol extracts of Morus alba L. (MA) and Angelica keiskei Koidz. (AK) leaves and their mixtures (MIX) were evaluated in vitro and in vivo. Our results showed that MIX increased 5-aminoimidazole-4-carboxamide ribonucleotide-induced C2C12 myotube thinning, and enhanced soleus and gastrocnemius muscle thickness compared to each extract alone in dexamethasone-induced muscle atrophy Sprague Dawley rats. In addition, although MA and AK substantially improved grip strength and histological changes for dexamethasone-induced muscle atrophy in vivo, the efficacy was superior in the MIX-treated group. Moreover, MIX further increased the expression levels of myogenic factors (MyoD and myogenin) and decreased the expression levels of E3 ubiquitin ligases (atrogin-1 and muscle-specific RING finger protein-1) in vitro and in vivo compared to the MA- and AK-alone treatment groups. Furthermore, MIX increased the levels of phosphorylated phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), and mammalian target of rapamycin (mTOR) that were reduced by dexamethasone, and downregulated the expression of forkhead box O3 (FoxO3a) induced by dexamethasone. These results suggest that MIX has a protective effect against muscle atrophy by enhancing muscle protein anabolism through the activation of the PI3K/Akt/mTOR signaling pathway and attenuating catabolism through the inhibition of FoxO3a.

Systematic approaches to identify functional genes using the FOX-hunting system in Chinese cabbage (FOX hunting system을 이용한 배추 기능유전자 탐색)

  • Lee, In-Hoo;Jung, Yu-Jin;Park, Jong-In;Nou, Ill-Sup;Kang, Kwon-Kyoo
    • Journal of Plant Biotechnology
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    • v.37 no.2
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    • pp.174-185
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    • 2010
  • Full-length cDNAs are essential for the correct annotation of genomic sequences and for the functional analysis of genes and their products. To elucidate the functions of a large population of Chinese cabbage (Brassica rapa) genes and to search efficiently for agriculturally useful genes, we have been taking advantage of the full-length cDNA Over-eXpresser (FOX) gene hunting system. With oligo dT column it purify the each mRNA from the flower organs, leaf and stem tissue. And about 120,000 cDNAs from the library were transformed into $\lambda$-pFLCIII-F vector. Of which 115,000 cDNAs from the library were transformed into T-DNA binary vector, pBigs for transformation study. We used normalized full-length cDNA and introduced each cDNA into Arabidopsis by in planta transformation. Full-length Chinese cabbage cDNAs were expressed independently under the CaMV 35S promoter in Arabidopsis. Selfed seeds were harvested from transgenic Arabidopsis. We had selected 2,500 transgenic plants by hygromycin antibiotic tolerant test, and obtained a number of transgenic mutants. Each transgenic Arabidopsis was investigated in morphological changes, fertility and leaf colour. As a result, 285 possible morphological mutants were identified. Introduced cDNA was isolated by PCR amplification of the genomic DNA from the transgenic mutants. Sequencing result and BLAST analysis showed that most of the introduced cDNA were complete cDNAs and functional genes. Also, we examined the effect of Bromelain on enhancing resistance to soft rot in transgenic Chinese cabbage 'Osome'. The bromelain gene identified from FOX hunting system was transformed into Chinese cabbage using Agrobacterium methods. Transformants were screened by PCR, then RT-PCR and real time PCR were performed to analyze gene expression of cysteine protease in the T1 and T2 generations. The anti-bacterial activity of bromelain was tested in Chinese cabbages infected with soft rot bacteria. The results showed that the over-expressed bromelain gene from pineapple conferred enhanced resistance to soft rot in Chinese cabbage.

Role of stearyl-coenzyme A desaturase 1 in mediating the effects of palmitic acid on endoplasmic reticulum stress, inflammation, and apoptosis in goose primary hepatocytes

  • Tang, Bincheng;Qiu, Jiamin;Hu, Shenqiang;Li, Liang;Wang, Jiwen
    • Animal Bioscience
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    • v.34 no.7
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    • pp.1210-1220
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    • 2021
  • Objective: Unlike mammals, goose fatty liver shows a strong tolerance to fatty acids without obvious injury. Stearyl-coenzyme A desaturase 1 (SCD1) serves crucial role in desaturation of saturated fatty acids (SAFs), but its role in the SAFs tolerance of goose hepatocytes has not been reported. This study was conducted to explore the role of SCD1 in regulating palmitic acid (PA) tolerance of goose primary hepatocytes. Methods: 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide was examined to reflect the effect of PA on hepatocytes viability, and quantitative polymerase chain reaction was used to detect the mRNA levels of several genes related to endoplasmic reticulum (ER) stress, inflammation, and apoptosis, and the role of SCD1 in PA tolerance of goose hepatocytes was explored using RNA interfere. Results: Our results indicated that goose hepatocytes exhibited a higher tolerant capacity to PA than human hepatic cell line (LO2 cells). In goose primary hepatocytes, the mRNA levels of fatty acid desaturation-related genes (SCD1 and fatty acid desaturase 2) and fatty acid elongate enzyme-related gene (elongase of very long chain fatty acids 6) were significantly upregulated with 0.6 mM PA treatment. However, in LO2 cells, expression of ER stress-related genes (x box-binding protein, binding immunoglobulin protein, and activating transcription factor 6), inflammatory response-related genes (interleukin-6 [IL-6], interleukin-1β [IL-1β], and interferon-γ) and apoptosis-related genes (bcl-2-associated X protein, b-cell lymphoma 2, Caspase-3, and Caspase-9) was significantly enhanced with 0.6 mM PA treatment. Additionally, small interfering RNA (siRNA) mediated downregulation of SCD1 significantly reduced the PA tolerance of goose primary hepatocytes under the treatment of 0.6 mM PA; meanwhile, the mRNA levels of inflammatory-related genes (IL-6 and IL-1β) and several key genes involved in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT), forkhead box O1 (FoxO1), mammalian target of rapamycin and AMPK pathways (AKT1, AKT2, FoxO1, and sirtuin 1), as well as the protein expression of cytochrome C and the apoptosis rate were upregulated. Conclusion: In conclusion, our data suggested that SCD1 was involved in enhancing the PA tolerance of goose primary hepatocytes by regulating inflammation- and apoptosis-related genes expression.

Rapamycin-resistant and torin-sensitive mTOR signaling promotes the survival and proliferation of leukemic cells

  • Park, Seohyun;Sim, Hyunsub;Lee, Keunwook
    • BMB Reports
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    • v.49 no.1
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    • pp.63-68
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    • 2016
  • The serine/threonine kinase mTOR is essential for the phosphoinositide 3-kinases (PI3K) signaling pathway, and regulates the development and function of immune cells. Aberrant activation of mTOR signaling pathway is associated with many cancers including leukemia. Here, we report the contributions of mTOR signaling to growth of human leukemic cell lines and mouse T-cell acute leukemia (T-ALL) cells. Torin, an ATP-competitive mTOR inhibitor, was found to have both cytotoxic and cytostatic effects on U-937, THP-1, and RPMI-8226 cells, but not on Jurkat or K-562 cells. All cells were relatively resistant to rapamycin even with suppressed activity of mTOR complex 1. Growth of T-ALL cells induced by Notch1 was profoundly affected by torin partially due to increased expression of Bcl2l11 and Bbc3. Of note, activation of Akt or knockdown of FoxO1 mitigated the effect of mTOR inhibition on T-ALL cells. Our data provide insight on the effect of mTOR inhibitors on the survival and proliferation of leukemic cells, thus further improving our understanding on cell-context-dependent impacts of mTOR signaling. [BMB Reports 2016; 49(1): 63-68]

FADD Phosphorylation Modulates Blood Glucose Levels by Decreasing the Expression of InsulinDegrading Enzyme

  • Lin, Yan;Liu, Jia;Chen, Jia;Yao, Chun;Yang, Yunwen;Wang, Jie;Zhuang, Hongqin;Hua, Zi-Chun
    • Molecules and Cells
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    • v.43 no.4
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    • pp.373-383
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    • 2020
  • Our previous study revealed a novel role of Fas-associated death domain-containing protein (FADD) in islet development and insulin secretion. Insulin-degrading enzyme (IDE) is a zinc metalloprotease that selectively degrades biologically important substrates associated with type 2 diabetes (T2DM). The current study was designed to investigate the effect of FADD phosphorylation on IDE. We found that the mRNA and protein levels of IDE were significantly downregulated in FADD-D mouse livers compared with control mice. Quantitative real-time polymerase chain reaction analysis showed that FADD regulates the expression of IDE at the transcriptional level without affecting the stability of the mRNA in HepG2 cells. Following treatment with cycloheximide, the IDE protein degradation rate was found to be increased in both FADD-D primary hepatocytes and FADD-knockdown HepG2 cells. Additionally, IDE expression levels were reduced in insulin-stimulated primary hepatocytes from FADD-D mice compared to those from control mice. Moreover, FADD phosphorylation promotes nuclear translocation of FoxO1, thus inhibiting the transcriptional activity of the IDE promoter. Together, these findings imply a novel role of FADD in the reduction of protein stability and expression levels of IDE.

The Inverse Laplace Transform of a Wide Class of Special Functions

  • Soni, Ramesh Chandra;Singh, Deepika
    • Kyungpook Mathematical Journal
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    • v.46 no.1
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    • pp.49-56
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    • 2006
  • The aim of the present work is to obtain the inverse Laplace transform of the product of the factors of the type $s^{-\rho}\prod\limit_{i=1}^{\tau}(s^{li}+{\alpha}_i)^{-{\sigma}i}$, a general class of polynomials an the multivariable H-function. The polynomials and the functions involved in our main formula as well as their arguments are quite general in nature. On account of the general nature of our main findings, the inverse Laplace transform of the product of a large variety of polynomials and numerous simple special functions involving one or more variables can be obtained as simple special cases of our main result. We give here exact references to the results of seven research papers that follow as simple special cases of our main result.

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