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https://www.readbyqxmd.com/read/29694832/cdc14-phosphatase-promotes-torc1-regulated-autophagy-in-yeast
#1
Akihiro Kondo, Md Golam Mostofa, Katsuya Miyake, Mashu Terasawa, Nafisa Islam, Akter M S T Yeasmin, Talukdar Muhammad Waliullah, Tomotake Kanki, Takashi Ushimaru
Cdc14 protein phosphatase is critical for late mitosis progression in budding yeast, although its orthologs in other organisms, including mammalian cells, function as stress-responsive phosphatases. We found herein unexpected roles of Cdc14 in autophagy induction after nutrient starvation and target of rapamycin complex 1 (TORC1) kinase inactivation. TORC1 kinase phosphorylates Atg13 to repress autophagy in nutrient-rich conditions, but if TORC1 becomes inactive upon nutrient starvation or rapamycin treatment, Atg13 is rapidly dephosphorylated and autophagy is induced...
April 22, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29693767/7-ketocholesterol-impairs-phagocytosis-and-efferocytosis-via-dysregulation-of-phosphatidylinositol-4-5-bisphosphate
#2
Stella M Lu, Gregory D Fairn
The plasma membrane is inhomogeneously organized containing both highly ordered and disordered nanodomains. 7-Ketocholesterol (7KC), an oxysterol formed from the non-enzymatic oxidation of cholesterol, is a potent disruptor of membrane order. Importantly, 7KC is a component of oxidized LDL and accumulates in macrophage and foam cells found in arterial plaques. Using a murine macrophage cell line, J774, we report that both IgG-mediated and phosphatidylserine (PtdSer)-mediated phagocytic pathways are inhibited by the accumulation of 7KC...
April 24, 2018: Traffic
https://www.readbyqxmd.com/read/29692761/ribosome-shunting-polycistronic-translation-and-evasion-of-antiviral-defenses-in-plant-pararetroviruses-and-beyond
#3
REVIEW
Mikhail M Pooggin, Lyubov A Ryabova
Viruses have compact genomes and usually translate more than one protein from polycistronic RNAs using leaky scanning, frameshifting, stop codon suppression or reinitiation mechanisms. Viral (pre-)genomic RNAs often contain long 5'-leader sequences with short upstream open reading frames (uORFs) and secondary structure elements, which control both translation initiation and replication. In plants, viral RNA and DNA are targeted by RNA interference (RNAi) generating small RNAs that silence viral gene expression, while viral proteins are recognized by innate immunity and autophagy that restrict viral infection...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29692710/pp242-counteracts-glioblastoma-cell-proliferation-migration-invasiveness-and-stemness-properties-by-inhibiting-mtorc2-akt
#4
Carmen Mecca, Ileana Giambanco, Stefano Bruscoli, Oxana Bereshchenko, Bernard Fioretti, Carlo Riccardi, Rosario Donato, Cataldo Arcuri
Glioblastoma multiforme (GBM) is the most malignant brain tumor and is associated with poor prognosis due to its thorny localization, lack of efficacious therapies and complex biology. Among the numerous pathways driving GBM biology studied so far, PTEN/phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) signaling plays a pivotal role, as it controls cell survival, proliferation and metabolism and is involved in stem cell maintenance. In front of recent and numerous evidences highlighting mTOR upregulation in GBM, all the strategies developed to inhibit this pathway have been substantially unsuccessful...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29692266/insights-into-the-biological-evaluation-of-pterocarpanquinones-and-carbapterocarpans-with-anti-tumor-activity-against-mdr-leukemias
#5
Vivian M Rumjanek, Raquel C Maia, Eduardo J Salustiano, Paulo R R Costa
In an attempt to find anticancer agents that could overcome multidrug resistance (MDR), two new classes of modified isoflavonoids were designed and synthesized, and their effectiveness evaluated against a vast array of tumor cell lines. Pterocarpanquinone (LQB-118) and 11a-aza-5-carbapterocarpan (LQB-223) were the most promising. LQB-118 induced cell death, in vitro, in the mM range, to a number of human cancer cell lines as well as to fresh tumor cells obtained from patients with acute or chronic myeloid leukemia, independent on whether they exhibit or not the MDR phenotype...
April 20, 2018: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29691838/ros-autophagy-pathway-mediates-monocytes-human-umbilical-vein-endothelial-cells-adhesion-induced-by-apelin-13
#6
Meiqing Liu, Hening Li, Qun Zhou, Hong Zhao, Deguan Lv, Jiangang Cao, Jinyong Jiang, Mingzhu Tang, Di Wu, Jiaqi Liu, Lele Wu, Haoliang Hu, Lu He, Shifang Huang, Zhe Chen, Lanfang Li, Linxi Chen
Apelin is the endogenous ligand of APJ receptor. Both monocytes (MCs) and human umbilical vein endothelial cells (HUVECs) express apelin and APJ, which play important roles in the physiological processes of atherosclerosis. Our previous research indicated that apelin-13 promoted MCs-HUVECs adhesion. Here, we further explore the mechanism responsible for MCs-HUVECs adhesion induced by apelin-13. Apelin-13 promoted reactive oxygen species (ROS) generation and NOX4 expression in HUVECs. Apelin-13 inducedautophagy, increased proteins beclin1 and LC3-II/I expression and induced autophagy flux in HUVECs, which was blocked by NAC, catalase and DPI...
April 24, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29691711/biomechanics-and-mechanical-signaling-in-the-ovary-a-systematic-review
#7
REVIEW
Jaimin S Shah, Reem Sabouni, Kamaria C Cayton Vaught, Carter M Owen, David F Albertini, James H Segars
PURPOSE: Mammalian oogenesis and folliculogenesis share a dynamic connection that is critical for gamete development. For maintenance of quiescence or follicular activation, follicles must respond to soluble signals (growth factors and hormones) and physical stresses, including mechanical forces and osmotic shifts. Likewise, mechanical processes are involved in cortical tension and cell polarity in oocytes. Our objective was to examine the contribution and influence of biomechanical signaling in female mammalian gametogenesis...
April 24, 2018: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/29691292/phenformin-induced-mitochondrial-dysfunction-sensitizes-hepatocellular-carcinoma-for-dual-inhibition-of-mtor
#8
Sonia Rosa Veiga, Xuemei Ge, Carol A Mercer, María Isabel Hernández-Alvarez, Hala Elnakat Thomas, Javier Hernández-Losa, Santiago Ramón Y Cajal, Antonio Zorzano, George Thomas, Sara C Kozma
PURPOSE: Hepatocellular carcinoma (HCC) ranks second in cancer mortality and has limited therapeutic options. We recently described the synergistic effect of allosteric and ATP-site competitive inhibitors against the mammalian target of rapamycin (mTOR) for the treatment of HCC. However, such inhibitors induce glycemia and increase mitochondrial efficiency. Here we determined whether the mitochondrial complex I inhibitor Phenformin could reverse both side effects, impose an energetic-stress on cancer cells and suppress the growth of HCC...
April 24, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29689288/self-assembled-amphiphilic-zein-lactoferrin-micelles-for-tumor-targeted-co-delivery-of-rapamycin-and-wogonin-to-breast-cancer
#9
Sally A Sabra, Ahmed O Elzoghby, Salah A Sheweita, Medhat Haroun, Maged W Helmy, Maha A Eldemellawy, Ying Xia, David Goodale, Alison L Allan, Sohrab Rohani
Protein-based micelles have shown significant potential for tumor-targeted delivery of anti-cancer drugs. In this light, self-assembled nanocarriers based on GRAS (Generally recognized as safe) amphiphilic protein co-polymers were synthesized via carbodiimide coupling reaction. The new nano-platform is composed of the following key components: i) hydrophobic zein core to encapsulate the hydrophobic drugs rapamycin (RAP) and wogonin (WOG) with high encapsulation efficiency, ii) hydrophilic lactoferrin (Lf) corona to enhance the tumor targeting, and prolong systemic circulation of the nanocarriers, and iii) glutaraldehyde (GLA)-crosslinking to reduce the particle size and improve micellar stability...
April 21, 2018: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/29689132/alcohol-delays-the-onset-of-puberty-in-the-female-rat-by-altering-key-hypothalamic-events
#10
Vinod K Srivastava, Jill K Hiney, William L Dees
BACKGROUND: Because alcohol (ALC) delays signs of pubertal development, we assessed the time course of events associated with the synthesis of critical hypothalamic peptides that regulate secretion of luteinizing hormone-releasing hormone (LHRH), the peptide that drives the pubertal process. METHODS: Immature female rats were administered either lab chow or Bio-Serve isocaloric control or ALC liquid diets from 27 through 33 days of age. On days 28, 29, 31 and 33 animals were killed by decapitation and tissue blocks containing the medial basal hypothalamus (MBH) and the rostral hypothalamic area (RHA) were isolated and stored frozen until assessed by Western blot analysis...
April 24, 2018: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/29687904/unitary-physiology
#11
John S Torday, William B Miller
The common relationships among a great variety of biological phenomena seem enigmatic when considered solely at the level of the phenotype. The deep connections in physiology, for example, between the effects of maternal food restriction in utero and the subsequent incidence of metabolic syndrome in offspring, the effects of microgravity on cell polarity and reproduction in yeast, stress effects on jellyfish, and their endless longevity, or the relationship between nutrient abundance and the colonial form in slime molds, are not apparent by phenotypic observation...
March 25, 2018: Comprehensive Physiology
https://www.readbyqxmd.com/read/29687779/selective-eradication-of-cancer-displaying-hyperactive-akt-by-exploiting-the-metabolic-consequences-of-akt-activation
#12
Veronique Nogueira, Krushna Chandra Patra, Nissim Hay
Akt activation in human cancers exerts chemoresistance, but pan-Akt inhibition elicits adverse consequences. We exploited the consequences of Akt-mediated mitochondrial and glucose metabolism to selectively eradicate and evade chemoresistance of prostate cancer displaying hyperactive Akt. PTEN-deficient prostate cancer cells that display hyperactivated Akt have high intracellular reactive oxygen species (ROS) levels, which are due, in part, to Akt-dependent increase of oxidative phosphorylation. High intracellular ROS levels selectively sensitize cells displaying hyperactive Akt to ROS-induced cell death enabling a therapeutic strategy combining a ROS inducer and rapamycin in PTEN-deficient prostate tumors in mouse models...
April 24, 2018: ELife
https://www.readbyqxmd.com/read/29686643/inhibition-of-mtorc1-signaling-reverts-cognitive-and-affective-deficits-in-a-mouse-model-of-parkinson-s-disease
#13
Débora Masini, Alessandra Bonito-Oliva, Maëlle Bertho, Gilberto Fisone
Non-motor symptoms, including cognitive deficits and affective disorders, are frequently diagnosed in Parkinson's disease (PD) patients and are only partially alleviated by dopamine replacement therapy. Here, we used a 6-hydroxydopamine (6-OHDA) mouse model of PD to examine the effects exerted on non-motor symptoms by inhibition of the mammalian target of rapamycin complex 1 (mTORC1), which is involved in the control of protein synthesis, cell growth, and metabolism. We show that rapamycin, which acts as an allosteric inhibitor of mTORC1, counteracts the impairment of novel object recognition...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29686621/pravastatin-protects-against-avascular-necrosis-of-femoral-head-via-autophagy
#14
Yun Liao, Ping Zhang, Bo Yuan, Ling Li, Shisan Bao
Autophagy serves as a stress response and may contribute to the pathogenesis of avascular necrosis of the femoral head induced by steroids. Statins promote angiogenesis and ameliorate endothelial functions through apoptosis inhibition and necrosis of endothelial progenitor cells, however the process used by statins to modulate autophagy in avascular necrosis of the femoral head remains unclear. This manuscript determines whether pravastatin protects against dexamethasone-induced avascular necrosis of the femoral head by activating endothelial progenitor cell autophagy...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29686608/modulation-of-autophagy-by-a-small-molecule-inverse-agonist-of-err%C3%AE-is-neuroprotective
#15
S N Suresh, Aravinda K Chavalmane, Malini Pillai, Veena Ammanathan, D J Vidyadhara, Haorei Yarreiphang, Shashank Rai, Abhik Paul, James P Clement, Phalguni A Alladi, Ravi Manjithaya
Mechanistic insights into aggrephagy, a selective basal autophagy process to clear misfolded protein aggregates, are lacking. Here, we report and describe the role of Estrogen Related Receptor α (ERRα, HUGO Gene Nomenclature ESRRA), new molecular player of aggrephagy, in keeping autophagy flux in check by inhibiting autophagosome formation. A screen for small molecule modulators for aggrephagy identified ERRα inverse agonist XCT 790, that cleared α-synuclein aggregates in an autophagy dependent, but mammalian target of rapamycin (MTOR) independent manner...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29686269/lysosomal-damage-after-spinal-cord-injury-causes-accumulation-of-ripk1-and-ripk3-proteins-and-potentiation-of-necroptosis
#16
Shuo Liu, Yun Li, Harry M C Choi, Chinmoy Sarkar, Eugene Y Koh, Junfang Wu, Marta M Lipinski
Necroptosis, a regulated necrosis pathway mediated by the receptor-interacting protein kinases 1 and 3 (RIPK1 and RIPK3), is induced following spinal cord injury (SCI) and thought to contribute to neuronal and glial cell death. However, mechanisms leading to activation of necroptosis after SCI remain unclear. We have previously shown that autophagy, a catabolic pathway facilitating degradation of cytoplasmic proteins and organelles in a lysosome-dependent manner, is inhibited following SCI in rats. Our current data confirm that inhibition of autophagy also occurs after thoracic contusive SCI in the mouse model, as indicated by accumulation of both the autophagosome marker, LC3-II and autophagy cargo protein, p62/SQSTM1...
April 23, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29686055/raptor-controls-developmental-growth-transitions-by-altering-the-hormonal-and-metabolic-balance
#17
Mohamed A Salem, Yan Li, Krzysztof Bajdzienko, Joachim Fisahn, Mutsumi Watanabe, Rainer Hoefgen, Mark Aurel Schöttler, Patrick Giavalisco
Vegetative growth requires the systemic coordination of numerous cellular processes, which are controlled by regulatory proteins that monitor extra- and intra-cellular cues and translate them into growth decisions. In eukaryotes, one of the central factors regulating growth is the Ser/Thr protein kinase Target of Rapamycin (TOR), which forms complexes with regulatory proteins. To understand the function of one such regulatory protein, Regulatory-Associated Protein of TOR 1B (RAPTOR1B) in plants, we analyzed the effect of raptor1b mutations on growth and physiology in Arabidopsis thaliana by detailed phenotyping, metabolomic, lipidomic, and proteomic analysis...
April 23, 2018: Plant Physiology
https://www.readbyqxmd.com/read/29686050/lysosomal-protein-lamtor1-controls-innate-immune-responses-via-nuclear-translocation-of-transcription-factor-eb
#18
Yoshitomo Hayama, Tetsuya Kimura, Yoshito Takeda, Shigeyuki Nada, Shohei Koyama, Hyota Takamatsu, Sujin Kang, Daisuke Ito, Yohei Maeda, Masayuki Nishide, Satoshi Nojima, Hana Sarashina-Kida, Takashi Hosokawa, Yuhei Kinehara, Yasuhiro Kato, Takeshi Nakatani, Yoshimitsu Nakanishi, Takeshi Tsuda, Taro Koba, Masato Okada, Atsushi Kumanogoh
Amino acid metabolism plays important roles in innate immune cells, including macrophages. Recently, we reported that a lysosomal adaptor protein, Lamtor1, which serves as the scaffold for amino acid-activated mechanistic target of rapamycin complex 1 (mTORC1), is critical for the polarization of M2 macrophages. However, little is known about how Lamtor1 affects the inflammatory responses that are triggered by the stimuli for TLRs. In this article, we show that Lamtor1 controls innate immune responses by regulating the phosphorylation and nuclear translocation of transcription factor EB (TFEB), which has been known as the master regulator for lysosome and autophagosome biogenesis...
April 23, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29685622/early-dietary-restriction-in-rats-alters-skeletal-muscle-tuberous-sclerosis-complex-ribosomal-s6-and-mitogen-activated-protein-kinase
#19
Kara L Calkins, Shanthie Thamotharan, Yun Dai, Bo-Chul Shin, Satish C Kalhan, Sherin U Devaskar
Intrauterine growth restriction is linked to decreased lean body mass and insulin resistance. The mammalian target of rapamycin (mTOR) regulates muscle mass and glucose metabolism; however, little is known about maternal dietary restriction and skeletal muscle mTOR in offspring. We hypothesized that early dietary restriction would decrease skeletal muscle mass and mTOR in the suckling rat. To test this hypothesis, ab libitum access to food or dietary restriction during gestation followed by postnatal cross-fostering to a dietary-restricted or ad libitum-fed rat dam during lactation generated 4 groups: control (CON), intrauterine dietary restricted (IUDR), postnatal dietary restricted (PNDR), and IUDR+PNDR (IPDR)...
March 23, 2018: Nutrition Research
https://www.readbyqxmd.com/read/29685053/cardioprotective-and-anti-aggregatory-effects-of-levosimendan-on-isoproterenol-induced-myocardial-injury-in-high-fat-fed-rats-involves-modulation-of-pi3k-akt-mtor-signaling-pathway-and-inhibition-of-apoptosis-comparison-to-cilostazol
#20
Mona K Tawfik, Mohamed K El-Kherbetawy, Samy Makary
Hyperlipidemia and hypercoagulability states are linked with the increased risks of myocardial infarction (MI). Levosimendan has vasorelaxant and anti-aggregatory properties. The present study evaluated the anti-aggregatory and cardioprotective effects of levosimendan versus cilostazol in high-fat diet (HFD)-fed rats subjected to isoproterenol-induced MI. Rats were assigned to normal, HFD, HFD + isoproterenol, HFD + isoproterenol + cilostazol, and HFD + isoproterenol + levosimendan. The present study investigated the anti-aggregatory effect of both levosimendan and cilostazol and revealed that both drugs attenuated the severity of platelet aggregation...
January 1, 2018: Journal of Cardiovascular Pharmacology and Therapeutics
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