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Hye Jin Kim, Won Jun Lee
PURPOSE: Postmenopausal women are highly susceptible to diseases, such as obesity, type 2 diabetes, osteoporosis, or skeletal muscle atrophy and many people recognize the need for regular physical activity. Aerobic exercise training is known to improve the oxidative capacity and insulin sensitivity of skeletal muscles. This study aimed to investigate the role of low-intensity aerobic exercise training on skeletal muscle protein degradation or synthesis in the plantaris muscles of high-fat-fed ovariectomized rats...
September 30, 2017: Journal of Exercise Nutrition & Biochemistry
Shuguang Li, Yixiang Li, Lin Xiang, Jing Dong, Min Liu, Guangda Xiang
OBJECTIVE: To investigate that short-term treatment of sildenafil can induce browning of subcutaneous white adipose tissue (sWAT) in human adults. DESIGN: A randomized, double-blinded, placebo-controlled, parallel group trial. METHODS: Sixteen eligibility overweight male subjects were recruited, comparing 100 mg/day sildenafil versus an identical placebo therapy for 7 days. sWAT samples were collected from subjects before and after 7-day sildenafil or placebo intervention...
October 3, 2017: Metabolism: Clinical and Experimental
Jinghui Liu, Chun Xu, Shaofeng Zhang, Haoyan Li, Kele Chen, Pu Huang, Zonglou Guo, Lihong Xu
Microcystin-LR (MC-LR) is a cyanobacteria-derived heptapeptide that has been commonly characterized as a hepatotoxin. Although the liver is a primary organ in glucose homeostasis, the effect of MC-LR on glucose metabolism remains unclear. In this study, the human liver cell line HL7702 and ICR mice were exposed to various concentrations of MC-LR for 24 h, and the proteins involved in insulin signaling were investigated. The results showed that MC-LR treatment induced the hyperphosphorylation of insulin receptor substrate 1 (IRS1) at several serine sites, S307, S323, S636/639, and S1101 in HL7702 cells, and S302, S318, S632/635, and S1097 in mice livers...
October 6, 2017: Environmental Toxicology
Yalin Zhang, Peng Wang, Sen Lin, Yves Mercier, Huajun Yin, Yumo Song, Xiaoling Zhang, Lianqiang Che, Yan Lin, Shengyu Xu, Bin Feng, De Wu, Zhengfeng Fang
Mechanistic target of rapamycin complex1 (mTORC1) activation and protein synthesis varied with methionine sources; however, the related mechanisms are largely unknown. Porcine mammary epithelial cells (PMEC) and mammary tissue slices (MTS) were used to test whether methionine precursors differ in providing the available methionine and thus differ in mTORC1 signaling-associated protein synthesis. PMEC with methionine deprivation for 8 h and MTS from lactating sows were cultured for 24 and 2 h, respectively, with treatment media without methionine (negative control, NC) or supplemented with 0...
October 5, 2017: Amino Acids
Małgorzata Kapral, Joanna Wawszczyk, Katarzyna Jesse, Monika Paul-Samojedny, Dariusz Kuśmierz, Ludmiła Węglarz
Abstract: AKT, a serine/threonine protein kinase and mammalian target of rapamycin (mTOR) plays a critical role in the proliferation and resistance to apoptosis that are essential to the development and progression of colon cancer. Therefore, AKT/mTOR signaling pathway has been recognized as an attractive target for anticancer therapy. Inositol hexaphosphate (InsP6), a natural occurring phytochemical, has been shown to have both preventive and therapeutic effects against various cancers, however, its exact molecular mechanisms of action are not fully understood...
October 3, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Babet van der Vaart, Josef Fischböck, Christine Mieck, Peter Pichler, Karl Mechtler, René H Medema, Stefan Westermann
The target of rapamycin complex 1 (TORC1) is a highly conserved multiprotein complex that functions in many cellular processes, including cell growth and cell cycle progression. In this study, we define a novel role for TORC1 as a critical regulator of nuclear microtubule (MT) dynamics in the budding yeast Saccharomyces cerevisiae This activity requires interactions between EB1 and CLIP-170 plus end-tracking protein (+TIP) family members with the TORC1 subunit Kog1/Raptor, which in turn allow the TORC1 proximal kinase Sch9/S6K1 to regulate the MT polymerase Stu2/XMAP215...
September 29, 2017: Journal of Cell Biology
Nathan Hodson, Chris McGlory, Sara Y Oikawa, Stewart Jeromson, Zhe Song, Markus A Ruegg, D Lee Hamilton, Stuart M Phillips, Andrew Philp
Mechanistic target of rapamycin (mTOR) resides as two complexes within skeletal muscle. mTOR complex 1 (mTORC1-Raptor positive) regulates skeletal muscle growth, whereas mTORC2 (Rictor positive) regulates insulin sensitivity. To examine the regulation of these complexes in human skeletal muscle, we utilised immunohistochemical analysis to study the localisation of mTOR complexes prior to and following protein-carbohydrate feeding (FED) and resistance exercise plus protein-carbohydrate feeding (EXFED) in unilateral exercise model...
September 27, 2017: American Journal of Physiology. Cell Physiology
Ran Hee Choi, Abigail McConahay, Ha-Won Jeong, Jamie L McClellan, Justin P Hardee, James A Carson, Michael F Hirshman, Laurie J Goodyear, Ho-Jin Koh
Skeletal muscle atrophy is associated with a disruption in protein turnover involving increased protein degradation and suppressed protein synthesis. Although it has been well studied that the IGF-1/PI3K/Akt pathway plays an essential role in the regulation of the protein turnover, molecule(s) that triggers the change in protein turnover still remains to be elucidated. TRB3 has been shown to inhibit Akt through direct binding. In this study, we hypothesized that TRB3 in mouse skeletal muscle negatively regulates protein turnover via the disruption of Akt and its downstream molecules...
September 27, 2017: Biochemical and Biophysical Research Communications
Kyosuke Nakayama, Atsushi Kanda, Ryoichi Tagawa, Chiaki Sanbongi, Shuji Ikegami, Hiroyuki Itoh
Bovine milk proteins have a low absorption rate due to gastric acid-induced coagulation. Acidified milk remains liquid under acidic conditions; therefore, the absorption rate of its protein may differ from that of untreated milk. To investigate how this would affect muscle protein synthesis (MPS), we compared MPS after ingestion of acidified versus skim milk in rats. Male Sprague-Dawley rats swam for 2 h and were immediately administered acidified or skim milk, then euthanized at 30, 60, 90, and 120 min afterwards...
September 27, 2017: Nutrients
Xin Zheng, Lin Feng, Wei-Dan Jiang, Pei Wu, Yang Liu, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Xiao-Qiu Zhou
The objective of this study was to evaluate the effects of dietary pyridoxine (PN) deficiency on growth performance, intestinal immune function and the potential regulation mechanisms in young grass carp (Ctenopharyngodon idella). Fish were fed six diets containing graded levels of PN (0.12-7.48 mg/kg) for 70 days. After that, a challenge test was conducted by infection of Aeromonas hydrophila for 14 days. The results showed that compared with the optimal PN level, PN deficiency: (1) reduced the production of innate immune components such as lysozyme (LZ), acid phosphatase (ACP), complements and antimicrobial peptides and adaptive immune components such as immunoglobulins in three intestinal segments of young grass carp (P < 0...
September 23, 2017: Fish & Shellfish Immunology
Yuyan Xiong, Gautham Yepuri, Jean-Pierre Montani, Xiu-Fen Ming, Zhihong Yang
The mitochondrial arginase type II (Arg-II) has been shown to interact with ribosomal protein S6 kinase 1 (S6K1) and mitochondrial p66(Shc) and to promote cell senescence, apoptosis and inflammation under pathological conditions. However, the impact of Arg-II on organismal lifespan is not known. In this study, we demonstrate a significant lifespan extension in mice with Arg-II gene deficiency (Arg-II(-/-)) as compared to wild type (WT) control animals. This effect is more pronounced in the females than in the males...
2017: Frontiers in Physiology
Clovis Chabert, Saadi Khochbin, Sophie Rousseaux, Rebecca Furze, Nicholas Smithers, Rab Prinjha, Uwe Schlattner, Christophe Pison, Hervé Dubouchaud
Some of the Chronic Obstructive Pulmonary Disease (COPD) patients engaged in exercise-based muscle rehabilitation programs are unresponsive. To unravel the respective role of chronic hypoxia and pulmonary inflammation on soleus muscle hypertrophic capacities, we challenged male Wistar rats to repeated lipopolysaccharide instillations, associated or not with a chronic hypoxia exposure. Muscle hypertrophy was initiated by bilateral ablation of soleus agonists 1 week before sacrifice. To understand the role played by the histone acetylation, we also treated our animals with an inhibitor of bromodomains and extra terminal proteins (I-BET) during the week after surgery...
September 21, 2017: Scientific Reports
Takashi K Ito, Chenhao Lu, Jacob Khan, Quy Nguyen, Heather Z Huang, Dayae Kim, James Phillips, Jo Tan, Yenna Lee, Tuyet Nguyen, Samy Khessib, Natalie Lim, Surapat Mekvanich, Joshua Oh, Victor V Pineda, Weirong Wang, Alessandro Bitto, Jonathan Y An, John F Morton, Mitsutoshi Setou, Warren C Ladiges, Matt Kaeberlein
The inactivation of ribosomal protein S6 kinase 1 (S6K1) recapitulates aspects of caloric restriction and mTORC1 inhibition to achieve prolonged longevity in invertebrate and mouse models. In addition to delaying normative aging, inhibition of mTORC1 extends the shortened lifespan of yeast, fly, and mouse models with severe mitochondrial disease. Here we tested whether disruption of S6K1 can recapitulate the beneficial effects of mTORC1 inhibition in the Ndufs4 knockout (NKO) mouse model of Leigh Syndrome caused by Complex I deficiency...
2017: Frontiers in Genetics
H Sadri, J Steinhoff-Wagner, Harald M Hammon, R M Bruckmaier, S Görs, H Sauerwein
The rates of protein turnover are higher during the neonatal period than at any other time in postnatal life. The mammalian target of rapamycin (mTOR) and the ubiquitin-proteasome system are key pathways regulating cellular protein turnover. The objectives of this study were (1) to elucidate the effect of feeding colostrum versus milk-based formula on the mRNA abundance of key components of the mTOR pathway and of the ubiquitin-proteasome system in skeletal muscle of neonatal calves and (2) to compare different muscles...
November 2017: Journal of Dairy Science
Naomi Maeda, Abdikarim Abdullahi, Brendan Beatty, Zameer Dhanani, Olasunkanmi A J Adegoke
The mechanistic (mammalian) target of rapamycin complex 1 (mTORC1) signaling is vital for optimal muscle mass and function. Although the significance of mTORC1 in stimulating muscle growth is unequivocal, evidence in support of its role during muscle regeneration is less clear. Here, we showed that the abundance (protein and mRNA) of the mTORC1/S6K1 substrate, programmed cell death protein 4 (PDCD4), is upregulated at the onset of differentiation of L6 and C2C12 cells. The increase in PDCD4 was not associated with any changes in S6K1 activation, but the abundance of beta transducing repeat-containing protein (β-TrCP), the ubiquitin ligase that targets PDCD4 for degradation, increased...
September 2017: Physiological Reports
E L Sun, C X Liu, Z X Ma, X Y Mou, X A Mu, Y H Ni, X L Li, D Zhang, Y R Ju
Small cell lung cancer (SCLC) is characterized by rapid growth rate and a tendency to metastasize to distinct sites of patients' bodies. The human serine/threonine kinase 33 (STK33) gene has shown its potency as a therapeutic target for prevention of lung carcinomas including non-small cell lung cancer (NSCLC), but its function in the oncogenesis and development of SCLC remains unrevealed. In the current study, it was hypothesized that STK33 played a key role in the proliferation, survival, and invasion of SCLC cells...
September 12, 2017: Neoplasma
Adi Y Berman, Subrata Manna, Naomi S Schwartz, Yardena E Katz, Yang Sun, Catherine A Behrmann, Jane J Yu, David R Plas, Anya Alayev, Marina K Holz
Estrogen-related receptor alpha (ERRα) is an orphan nuclear factor that is a master regulator of cellular energy metabolism. ERRα is overexpressed in a variety of tumors, including ovarian, prostate, colorectal, cervical and breast, and is associated with a more aggressive tumor and a worse outcome. In breast cancer, specifically, high ERRα expression is associated with an increased rate of recurrence and a poor prognosis. Because of the common functions of ERRα and the mTORC1/S6K1 signaling pathway in regulation of cellular metabolism and breast cancer pathogenesis, we focused on investigating the biochemical relationship between ERRα and S6K1...
2017: Signal Transduction and Targeted Therapy
Xue-Liang Wu, Li-Kun Wang, Dong-Dong Yang, Ming Qu, Yong-Jiang Yang, Fei Guo, Lei Han, Jun Xue
This study aims to investigate the effects of glucose transport l (Glut1) gene on proliferation, differentiation and apoptosis of colorectal cancer (CRC) cells by regulating the TGF-β/PI3K-AKT-mTOR signaling pathway. Immunohistochemistry was conducted to detect the positive Glut1 expression. Normal human CRC epithelial cells (CCD-18Co) and CRC cell line HCT116 were grouped into the control, blank, negative control (NC), and shGlut1-1 groups. RT-qPCR and Western blotting were performed to detect the expressions of Glut1, TGF-β1, PI3K, AKT, PTEN, mTOR, Bcl-2 and Bax...
September 8, 2017: Journal of Cellular Biochemistry
Xiaohui Gu, Xuejie Fu, Jihang Lu, Saijilafu, Bin Li, Zong-Ping Luo, Jianquan Chen
mTORC1 signaling not only plays important physiological roles in the regulation of proliferation and osteogenic differentiation of BMSCs, but also mediates exogenous Wnt-induced protein anabolism and osteoblast differentiation. However, the downstream effectors of the mTORC1 signaling in the above processes are still poorly understood. In this study, we explored the specific role of S6K1, one of the major targets of the mTORC1 pathway, in BMSCs self-renewal and osteogenic differentiation. We first found that S6K1 was active in primary mouse bone marrow stromal cells, and further activated upon osteogenic induction...
July 11, 2017: Journal of Cellular Biochemistry
Itziar M D Posada, Benoit Lectez, Farid A Siddiqui, Christina Oetken-Lindholm, Mukund Sharma, Daniel Abankwa
As a major growth factor transducer, Ras is an upstream activator of mTORC1, which further integrates nutrient and energy inputs. To ensure a contextual coupling of cell division via Ras/MAPK-signalling and growth via mTORC1-signalling, feedback loops from one pathway back to the other are required. Here we describe a novel feedback from mTORC1, which oppositely affects oncogenic H-ras- and K-ras-signalling output, and as a consequence stemness properties of tumourigenic cells. Amino acid stimulation of mTORC1 increases the processed form of SREBP1, a major lipidome regulator...
August 21, 2017: Scientific Reports
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