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https://www.readbyqxmd.com/read/29621478/hyperglycemia-induced-bcl-2-bax-mediated-apoptosis-of-schwann-cells-via-mtorc1-s6k1-inhibition-in-diabetic-peripheral-neuropathy
#1
Lin Zhu, Jun Hao, Meijuan Cheng, Cuihong Zhang, Chunxiu Huo, Yaping Liu, Wei Du, Xianghong Zhang
Schwann cell apoptosis is one of the characteristics of diabetic peripheral neuropathy (DPN). The mammalian target of rapamycin (mTOR) is a multifunctional signaling pathway that regulates cell apoptosis in various types of tissues and cells. To investigate whether the mTOR pathway is involved in cell apoptosis in the Schwann cells of DPN, diabetic mice and rat Schwann cells (RSC96) were chosen to detect phospho-mTOR (Ser 2448), phospho-S6K1 (Thr 389), phospho-4EBP1 (Thr 37/46), Bcl-2, Bax and cleaved caspase-3 by diverse pathological and biological techniques...
April 2, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29607575/regulation-of-muscle-protein-synthesis-in-an-in-vitro-cell-model-using-ex-vivo-human-serum
#2
Brian P Carson, Bijal Patel, Miryam Amigo-Benavent, Martina Pauk, Sunil Kumar Gujulla, Sylvia M Murphy, Patrick A Kiely, Philip M Jakeman
Human serum embodies the integrated systemic response to any condition or perturbation which may regulate muscle protein synthesis (MPS). Conditioning of media with human serum represents a physiologically relevant method of regulating MPS in vitro. The primary purpose of this study is the development of a model using ex vivo human serum to condition media and regulate MPS in in vitro skeletal muscle cells. Four young healthy males reported to the lab after overnight fast and were fed with 0.33 g.kg-1  BM whey protein...
April 1, 2018: Experimental Physiology
https://www.readbyqxmd.com/read/29587154/intracellular-osteopontin-negatively-regulates-toll-like-receptor-4-mediated-inflammatory-response-via-regulating-gsk3%C3%AE-and-4ebp1-phosphorylation
#3
Haiou Yang, Xingchen Ye, Xiaoqing Zhang, Xiaoliang Li, Qihua Fu, Zhenhua Tang
Toll-like receptors (TLRs) play an important role in host defense against invading pathogens. By initiating a signal transduction cascade, TLRs lead to the release of pro-inflammatory cytokines. However, the inappropriate activation of TLR signaling could result in inflammatory disorders or autoimmune diseases. Osteopontin (OPN) has been reported to be an inflammatory cytokine participating in cell-mediated immunity. However, the role of OPN in TLR-mediated immune responses is poorly understood. In the present study, OPN-deficient (OPN-/-) macrophages exhibited significantly higher levels of pro-inflammatory cytokines after stimulation with lipopolysaccharide (LPS)...
March 24, 2018: Cytokine
https://www.readbyqxmd.com/read/29554968/metformin-induces-autophagy-and-g0-g1-phase-cell-cycle-arrest-in-myeloma-by-targeting-the-ampk-mtorc1-and-mtorc2-pathways
#4
Yan Wang, Wenbin Xu, Zixun Yan, Weili Zhao, Jianqing Mi, Junmin Li, Hua Yan
BACKGROUND: Metformin is a commonly used drug for the treatment of diabetes. Accumulating evidence suggests that it exerts anti-tumor effects in many cancers, including multiple myeloma (MM); however, the underlying molecular mechanisms have not been clearly elucidated. METHODS: The anti-myeloma effects of metformin were evaluated using human MM cell lines (RPMI8226 and U266) in vitro and in vivo NOD-SCID murine xenograft MM model. Cell viability was assessed with CCK8 and cell proliferation was measured by EdU incorporation assay...
March 20, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29550428/a-ketogenic-amino-acid-rich-diet-benefits-mitochondrial-homeostasis-by-altering-the-akt-4ebp1-and-autophagy-signaling-pathways-in-the-gastrocnemius-and-soleus
#5
Jinpeng Li, Megumi Kanasaki, Ling Xu, Munehiro Kitada, Kenji Nagao, Yusuke Adachi, Hiroko Jinzu, Yasushi Noguchi, Miyuki Kohno, Keizo Kanasaki, Daisuke Koya
Muscle biology is important topic in diabetes research. We have reported that a diet with ketogenic amino acids rich replacement (KAAR) ameliorated high-fat diet (HFD)-induced hepatosteatosis via activation of the autophagy system. Here, we found that a KAAR ameliorated the mitochondrial morphological alterations and associated mitochondrial dysfunction induced by an HFD through induction of the AKT/4EBP1 and autophagy signaling pathways in both fast and slow muscles. The mice were fed with a standard HFD (30% fat in food) or an HFD with KAAR (HFDKAAR )...
March 14, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29545132/non-conventional-rottlerin-anticancer-properties
#6
REVIEW
Maioli E, Daveri E, Maellaro E, Ietta F, Cresti L, Valacchi G
In the past few years, we focused the interest on rottlerin, an old/new natural substance that, over the time, has revealed a number of cellular and molecular targets, all potentially implicated in the fight against cancer. Past and recent literature well demonstrated that rottlerin is an inhibitor of enzymes, transcription factors and signaling molecules that control cancer cell life and death. Although the rottlerin anticancer activity has been mainly ascribed to apoptosis and/or autophagy induction, recent findings unveiled the existence of additional mechanisms of toxicity...
March 12, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29508246/a-phase-ii-study-of-the-dual-mtor-inhibitor-mln0128-in-patients-with-metastatic-castration-resistant-prostate-cancer
#7
Laura Graham, Kalyan Banda, Alba Torres, Brett S Carver, Yu Chen, Katie Pisano, Greg Shelkey, Tracy Curley, Howard I Scher, Tamara L Lotan, Andrew C Hsieh, Dana E Rathkopf
Background MLN0128 is a first-in-class, dual mTOR inhibitor with potential to outperform standard rapalogs through inhibition of TORC1 and TORC2. This phase II study was designed to assess antitumor activity of MLN0128 in metastatic castration-resistant prostate cancer (mCRPC). Methods Eligible patients had mCRPC previously treated with abiraterone acetate and/or enzalutamide. Five patients started MLN0128 at 5 mg once daily, subsequently dose reduced to 4 mg because of toxicity. Four subsequent patients started MLN0128 at 4 mg daily...
March 6, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29507660/flt3-itd-induces-expression-of-pim-kinases-through-stat5-to-confer-resistance-to-the-pi3k-akt-pathway-inhibitors-on-leukemic-cells-by-enhancing-the-mtorc1-mcl-1-pathway
#8
Keigo Okada, Ayako Nogami, Shinya Ishida, Hiroki Akiyama, Cheng Chen, Yoshihiro Umezawa, Osamu Miura
FLT3-ITD is the most frequent tyrosine kinase mutation in acute myeloid leukemia (AML) associated with poor prognosis. We previously reported that activation of STAT5 confers resistance to PI3K/Akt inhibitors on the FLT3-ITD-positive AML cell line MV4-11 and 32D cells driven by FLT3-ITD (32D/ITD) but not by FLT3 mutated in the tyrosine kinase domain (32D/TKD). Here, we report the involvement of Pim kinases expressed through STAT5 activation in acquisition of this resistance. The specific pan-Pim kinase inhibitor AZD1208 as well as PIM447 in combination with the PI3K inhibitor GDC-0941 or the Akt inhibitor MK-2206 cooperatively downregulated the mTORC1/4EBP1 pathway, formation of the eIF4E/eIF4G complex, and Mcl-1 expression leading to activation of Bak and Bax to induce caspase-dependent apoptosis synergistically in these cells...
February 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29494292/paralytic-and-non-paralytic-muscle-adaptations-to-exercise-training-vs-high-protein-diet-in-individuals-with-long-standing-spinal-cord-injury
#9
Ceren Yarar-Fisher, Keith Fl Polston, Mualla Eraslan, Kathryn Y Henley, Gizem I Kinikli, C Scott Bickel, Samuel T Windham, Amie B McLain, Robert A Oster, Marcas M Bamman
This study compares the effects of an 8-week iso-caloric high protein (HP) diet versus a combination exercise (Comb-Ex) regimen on paralytic vastus lateralis (VL) and non-paralytic deltoid muscle in individuals with long-standing spinal cord injury (SCI). Fiber type distribution, cross-sectional area (CSA), levels of translation initiation signaling proteins (Erk-1/2, Akt, p70S6K1, 4EBP1, RPS6, and FAK), and lean thigh mass were analyzed at baseline and after the 8-week interventions. A total of 11 participants (C5-T12 levels, 21...
March 1, 2018: Journal of Applied Physiology
https://www.readbyqxmd.com/read/29492203/protein-biosynthesis-a-target-of-sorafenib-interferes-with-the-unfolded-protein-response-upr-and-ferroptosis-in-hepatocellular-carcinoma-cells
#10
Chloé Sauzay, Christophe Louandre, Sandra Bodeau, Frédéric Anglade, Corinne Godin, Zuzana Saidak, Jean-Xavier Fontaine, Cédric Usureau, Nathalie Martin, Roland Molinie, Julie Pascal, François Mesnard, Olivier Pluquet, Antoine Galmiche
Sorafenib is the first line treatment for advanced hepatocellular carcinoma (HCC). We explored its impact on the proteostasis of cancer cells, i.e. the processes that regulate the synthesis, maturation and turn-over of cellular proteins. We observed that sorafenib inhibits the production of the tumour marker alpha-foetoprotein (AFP) in two different HCC cell lines, an effect that correlated with a radical inhibition of protein biosynthesis. This effect was observed at clinically relevant concentrations of sorafenib and was not related to the effect of sorafenib on the transport of amino acids across the plasma membrane or the induction of the unfolded protein response (UPR)...
February 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29487419/functional-screening-of-fgfr4-driven-tumorigenesis-identifies-pi3k-mtor-inhibition-as-a-therapeutic-strategy-in-rhabdomyosarcoma
#11
Timothy McKinnon, Rosemarie Venier, Marielle Yohe, Sivasish Sindiri, Berkley E Gryder, Jack F Shern, Leah Kabaroff, Brendan Dickson, Krista Schleicher, Guillaume Chouinard-Pelletier, Serena Menezes, Abha Gupta, Xiaohu Zhang, Rajarashi Guha, Marc Ferrer, Craig J Thomas, Yuhong Wei, Dariush Davani, Cynthia J Guidos, Javed Khan, Rebecca A Gladdy
Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma and outcomes have stagnated, highlighting a need for novel therapies. Genomic analysis of RMS has revealed that alterations in the receptor tyrosine kinase (RTK)/RAS/PI3K axis are common and that FGFR4 is frequently mutated or overexpressed. Although FGFR4 is a potentially druggable receptor tyrosine kinase, its functions in RMS are undefined. This study tested FGFR4-activating mutations and overexpression for the ability to generate RMS in mice...
February 28, 2018: Oncogene
https://www.readbyqxmd.com/read/29484434/mir-33a-5p-enhances-the-sensitivity-of-lung-adenocarcinoma-cells-to-celastrol-by-regulating-mtor-signaling
#12
You-Jie Li, Yun-Xiao Sun, Rui-Min Hao, Pin Wu, Li-Jun Zhang, Xu Ma, Ying Ma, Ping-Yu Wang, Ning Xie, Shu-Yang Xie, Wei Chen
MicroRNAs (miRNAs or miRs) have recently become a popular focus of cancer research due to their ability to act as oncogenes or tumor suppressors. In the present study, miR‑33a‑5p expression was identified to be downregulated in lung adenocarcinoma samples compared with normal, which suggested that miR‑33a‑5p may serve as a tumor suppressor gene. Transfection with miR‑33a‑5p mimics inhibited the proliferation and migration of A549 and LTEP‑a‑2 cells and increased cellular apoptosis. A luciferase reporter assay confirmed that miR‑33a‑5p targets the 3'‑untranslated region of the mechanistic target of rapamycin (mTOR) gene...
February 14, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29483581/quantitative-assessment-of-liver-steatosis-and-affected-pathways-with-molecular-imaging-and-proteomic-profiling
#13
Yasuyo Urasaki, Chi Zhang, Ji-Xin Cheng, Thuc T Le
Current assessment of non-alcoholic fatty liver disease (NAFLD) with histology is time-consuming, insensitive to early-stage detection, qualitative, and lacks information on etiology. This study explored alternative methods for fast and quantitative assessment of NAFLD with hyperspectral stimulated Raman scattering (SRS) microscopy and nanofluidic proteomics. Hyperspectral SRS microscopy quantitatively measured liver composition of protein, DNA, and lipid without labeling and sensitively detected early-stage steatosis in a few minutes...
February 26, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29472733/androgen-interacts-with-exercise-through-the-mtor-pathway-to-induce-skeletal-muscle-hypertrophy
#14
Fanxing Zeng, Hua Zhao, Jingwen Liao
This study was designed to investigate the effects of exogenous androgen and resistance exercise on skeletal muscle hypertrophy and the role of the mammalian target of rapamycin (mTOR) signalling during the process. A total of 24 male Sprague-Dawley rats were randomly assigned to sham operation and dihydrotestosterone (DHT) implantation groups with subgroups subjected to sedentary conditions or resistance exercise (SHAM+SED, SHAM+EX, DHT+SED, and DHT+EX). The experimental procedure lasted for 10 days. The mRNA expression of androgen receptor (AR) and insulin-like growth factor I (IGF-I), the expression of myosin heavy chain (MHC), as well as the phosphorylation statuses of AR, mTOR, p70 ribosomal S6 kinase (p70S6K ), and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1) were determined in the white gastrocnemius muscle...
December 2017: Biology of Sport
https://www.readbyqxmd.com/read/29438034/c1qtnf3-in-the-murine-ovary-and-its-function-in-folliculogenesis
#15
Zhoufei Mao, Liuhong Yang, Xiaosheng Lu, Anni Tan, Yuxia Wang, Fei Ding, Luanjuan Xiao, Xufeng Qi, Yanhong Yu
C1q/tumor necrosis factor-related protein 3 (C1QTNF3) is a novel adipokine with modulating effects on metabolism, inflammation, and the cardiovascular system. C1QTNF3 expression levels in the sera and omental adipose tissues of women with PCOS are low compared to control subjects. However, the expression and function of C1QTNF3 in the ovary has not previously been examined. Here, we assessed the expression patterns of C1qtnf3 in the ovary and explored its role in folliculogenesis. The C1qtnf3 transcript abundance was higher in large follicles than in small follicles and was under the influence of gonadotropin...
February 1, 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/29435722/l-arginine-regulates-protein-turnover-in-porcine-mammary-epithelial-cells-to-enhance-milk-protein-synthesis
#16
Qingquan Ma, Shengdi Hu, Makoto Bannai, Guoyao Wu
Milk is an important food for mammalian neonates, but its insufficient production is a nutritional problem for humans and other animals. Recent studies indicate that dietary supplementation with L-arginine (Arg) increases milk production in mammals, including sows, rabbits, and cows. However, the underlying molecular mechanisms remain largely unknown. The present study was conducted with porcine mammary epithelial cells (PMECs) to test the hypothesis that Arg enhances milk protein synthesis via activation of the mechanistic target of rapamycin (mTOR) cell signaling...
February 12, 2018: Amino Acids
https://www.readbyqxmd.com/read/29434825/changes-in-inflammatory-and-oxidative-stress-factors-and-the-protein-synthesis-pathway-in-injured-skeletal-muscle-after-contusion
#17
Xiaoguang Liu, Zhigang Zeng, Linlin Zhao, Weihua Xiao, Peijie Chen
Injury of skeletal muscle, and particularly mechanically-induced damage, including contusion injury, frequently occurs in contact sports as well as in sports with accidental contact. Although the mechanisms of skeletal muscle regeneration are well understood, those involved in muscle contusion are not. A total of 40 male mice were randomly divided into control (n=8) and muscle contusion (n=32) groups. A muscle contusion model was established by weight-drop injury. Subsequently, the gastrocnemius muscles in the two groups were harvested at different times (1, 3, 7 and 14 days) post-injury...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29432553/short-term-heat-stress-altered-metabolism-and-insulin-signaling-in-skeletal-muscle
#18
Shanthi Ganesan, Corey M Summers, Sarah C Pearce, Nicholas K Gabler, Rudy J Valentine, Lance H Baumgard, Robert P Rhoads, Joshua T Selsby
Heat-related complications continue to be a major health concern for humans and animals and lead to potentially life-threatening conditions. Heat stress (HS) alters metabolic parameters and may alter glucose metabolism and insulin signaling. Therefore, the purpose of this investigation was to determine the extent to which 12 h of HS altered energetic metabolism in oxidative skeletal muscle. To address this, crossbred gilts (n=8/group) were assigned to one of three environmental treatments for 12 h: thermoneutral (TN; 21° C), heat stress (HS; 37° C), or pair-fed to HS counterparts but housed in TN conditions (PFTN)...
February 8, 2018: Journal of Animal Science
https://www.readbyqxmd.com/read/29416809/meta-analysis-of-the-prognostic-value-of-p-4ebp1-in-human-malignancies
#19
Tao Zhang, Jianrong Guo, Huili Li, Jiliang Wang
Phosphorylated 4E-binding protein 1 (p-4EBP1) is the inactivated form of 4EBP1, which is a downstream mediator in the mTOR signaling pathway and a vital factor in the synthesis of some oncogenic proteins. This meta-analysis was conducted to assess the predicative value of p-4EBP1 expression in human malignancies. The PubMed and Embase databases were carefully searched. Articles comparing the prognostic worthiness of different p-4EBP1 levels in human malignancies were collected for pooled analyses and methodologically appraised using the Newcastle-Ottawa Scale (NOS)...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29392448/effect-of-zinc-intake-on-hepatic-autophagy-during-acute-alcohol-intoxication
#20
Juan P Liuzzi, Vijaya Narayanan, Huong Doan, Changwon Yoo
Autophagy is a conserved mechanism that plays a housekeeping role by eliminating protein aggregates and damaged organelles. Recent studies have demonstrated that acute ethanol intoxication induces hepatic autophagy in mice. The effect of dietary zinc intake on hepatic autophagic flux during ethanol intoxication has not been evaluated using animal models. Herein, we investigated whether zinc deficiency and excess can affect autophagic flux in the liver in mice and in human hepatoma cells acutely exposed to ethanol...
February 1, 2018: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
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