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Mitochondria AND mTOR

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https://www.readbyqxmd.com/read/29675133/benefit-of-oleuropein-aglycone-for-alzheimer-s-disease-by-promoting-autophagy
#1
REVIEW
Joaquín G Cordero, Ramón García-Escudero, Jesús Avila, Ricardo Gargini, Vega García-Escudero
Alzheimer's disease is a proteinopathy characterized by accumulation of hyperphosphorylated Tau and β -amyloid. Autophagy is a physiological process by which aggregated proteins and damaged organelles are eliminated through lysosomal digestion. Autophagy deficiency has been demonstrated in Alzheimer's patients impairing effective elimination of aggregates and damaged mitochondria, leading to their accumulation, increasing their toxicity and oxidative stress. In the present study, we demonstrated by microarray analysis the downregulation of fundamental autophagy and mitophagy pathways in Alzheimer's patients...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29674750/publisher-correction-akt-mtor-signaling-modulates-the-dynamics-of-ire1-rnase-activity-by-regulating-er-mitochondria-contacts
#2
Miguel Sanchez-Alvarez, Miguel Angel Del Pozo, Chris Bakal
A correction to this article has been published and is linked from the HTML version of this paper. The error has not been fixed in the paper.
April 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29655701/apoptosis-and-pro-death-autophagy-induced-by-a-spirostanol-saponin-isolated-from-rohdea-chinensis-baker-n-tanaka-synonym-tupistra-chinensis-baker-on-hl-60-cells
#3
Xiaomin Yi, Limin Xiang, Yuying Huang, Yihai Wang, Xiangjiu He
BACKGROUND: Our previous study has revealed that the spirostanol saponins isolated from the rhizomes of Rohdea chinensis (Baker) N. Tanaka (synonym Tupistra chinensis Baker) (Convallariaceae) (a reputed folk medicine) exhibited potent antiproliferative activity. However, the underlying mechanism of purified saponins remains unclear. More studies are necessary to assess the apoptosis and autophagy activities of the saponins from R. chinensis and clarify their antiproliferative mechanisms...
March 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29649662/autophagy-attenuates-copper-induced-mitochondrial-dysfunction-by-regulating-oxidative-stress-in-chicken-hepatocytes
#4
Fan Yang, Jianzhao Liao, Ruonan Pei, Wenlan Yu, Qingyue Han, Ying Li, Jianying Guo, Lianmei Hu, Jiaqiang Pan, Zhaoxin Tang
Copper (Cu) is an essential trace element that is required for the catalysis of several cellular enzymes. Excessive Cu could induce hepatotoxicity in humans and multiple animals. The purpose of this study was to investigate the effects of autophagy machinery on Cu-induced hepatotoxicity. Chicken hepatocytes were cultured in medium in the absence and presence of Cu sulfate (CuSO4 ) (0, 10, 50, and 100 μM) for 0, 6, 12, and 24 h, and in the combination of CuSO4 and N-acetyl-l-cysteine (NAC) (1 mM), rapamycin (10 nM), and 3-methyladenine (3-MA) (5 mM) for 24 h...
March 29, 2018: Chemosphere
https://www.readbyqxmd.com/read/29627383/lpaat%C3%AE-agpat4-deficiency-impairs-maximal-force-contractility-in-soleus-and-alters-fibre-type-in-extensor-digitorum-longus-muscle
#5
Ryan M Bradley, Darin Bloemberg, Juan J Aristizabal Henao, Ashkan Hashemi, Andrew S Mitchell, Val A Fajardo, Catherine Bellissimo, Emily B Mardian, Eric Bombardier, Marie-France Paré, Katherine A Moes, Ken D Stark, A Russell Tupling, Joe Quadrilatero, Robin E Duncan
Lysophosphatidic acid acyltransferase (LPAAT) δ/acylglycerophosphate acyltransferase 4 is a mitochondrial enzyme and one of five homologues that catalyze the acyl-CoA-dependent synthesis of phosphatidic acid (PA) from lysophosphatidic acid. We studied skeletal muscle LPAATδ and found highest levels in soleus, a red oxidative fibre-type that is rich in mitochondria, and lower levels in extensor digitorum longus (EDL) (white glycolytic) and gastrocnemius (mixed fibre-type). Using Lpaatδ-deficient mice, we found no change in soleus or EDL mass, or in treadmill time-to-exhaustion compared to wildtype littermates...
April 5, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29616118/adenosine-induces-intrinsic-apoptosis-via-the-pi3k-akt-mtor-signaling-pathway-in-human-pharyngeal-squamous-carcinoma-fadu-cells
#6
Mi Suk Choi, Sung-Min Moon, Seul Ah Lee, Bo-Ram Park, Jae-Sung Kim, Do Kyung Kim, Yong Hwan Kim, Chun Sung Kim
Adenosine has been identified to occur abundantly intra-and extracellularly, and to exert diverse biological functions, including the suppression of cell proliferation and the induction of apoptosis. Adenosine has been reported to induce apoptosis in several cancer cell lines; however, to the best of our knowledge, the effect of adenosine on head and neck cancer cells has not been investigated. Therefore, the purpose of the present study was to evaluate whether adenosine exerts any anticancer effect via induction of apoptosis in human pharyngeal squamous carcinoma FaDu cells...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29609842/akebia-saponin-d-alleviates-hepatic-steatosis-through-bnip3-induced-mitophagy
#7
Li-Li Gong, Song Yang, Wen Zhang, Fei-Fei Han, Ya-Li Lv, Zi-Rui Wan, He Liu, Yang-Jie Jia, Ling-Ling Xuan, Li-Hong Liu
Akebia Saponin D (ASD) is the most abundant constituent of the rhizome of Dipsacus asper Wall. The prior studies have shown that ASD alleviates hepatic steatosis targeted at the modulation of autophagy and exerts hepatoprotective effects through mitochondria. However, it is still unclear which signal transduction pathway that ASD increase autophagy and protect the mitochondria. The purpose of this paper was to explore the mechanisms through which ASD alleviates hepatic steatosis. ASD significantly reduced lipid accumulation in BRL cells...
December 1, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29564224/the-role-of-mitochondrial-h-atp-synthase-in-cancer
#8
REVIEW
Pau B Esparza-Moltó, José M Cuezva
Cancer cells reprogram energy metabolism by boosting aerobic glycolysis as a main pathway for the provision of metabolic energy and of precursors for anabolic purposes. Accordingly, the relative expression of the catalytic subunit of the mitochondrial H+ -ATP synthase-the core hub of oxidative phosphorylation-is downregulated in human carcinomas when compared with its expression in normal tissues. Moreover, some prevalent carcinomas also upregulate the ATPase inhibitory factor 1 (IF1), which is the physiological inhibitor of the H+ -ATP synthase...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29554965/fucoxanthin-the-constituent-of-laminaria-japonica-triggers-ampk-mediated-cytoprotection-and-autophagy-in-hepatocytes-under-oxidative-stress
#9
Eun Jeong Jang, Sang Chan Kim, Ju-Hee Lee, Jong Rok Lee, Il Kon Kim, Su Youn Baek, Young Woo Kim
BACKGROUND: Laminaria japonica has frequently been used as a food supplement and drug in traditional oriental medicine. Among the major active constituents responsible for the bioactivities of L. japonica, fucoxanthin (FX) has been considered as a potential antioxidant. This study was conducted to examine the effects of L. japonica extract (LJE) or FX against oxidative stress on hepatocytes and to elucidate the overall their cellular mechanisms of the effects. METHODS: We constructed an in vitro model with the treatment of arachidonic acid (AA) + iron in HepG2 cells to stimulate the oxidative damage...
March 20, 2018: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29526763/lysosomes-support-the-degradation-signaling-and-mitochondrial-metabolism-necessary-for-human-epidermal-differentiation
#10
Christine L Monteleon, Tanvir Agnihotri, Ankit Dahal, Mingen Liu, Vito W Rebecca, Gregory L Beatty, Ravi K Amavaradi, Todd W Ridky
Keratinocytes undergo significant structural remodeling during epidermal differentiation, including a broad transformation of the proteome coupled with a reduction in total cellular biomass. This suggests that intracellular digestion of proteins and organelles is necessary for keratinocyte differentiation. Here, we use both genetic and pharmacologic approaches to demonstrate that autophagy and lysosomal functions are required for keratinocyte differentiation in organotypic human skin. Lysosomal activity was required for mTOR signaling and mitochondrial oxidative metabolism...
March 8, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29522724/long-term-treatment-with-anti-vegf-does-not-induce-cell-aging-in-primary-retinal-pigment-epithelium
#11
Johann Schottler, Niklas Randoll, Ralph Lucius, Amke Caliebe, Johann Roider, Alexa Klettner
Anti-Vascular Endothelial Growth Factor (VEGF) therapy is given repeatedly for an extended period of time to patients when treated for age-related macular degeneration. While short-term effects of anti-VEGF agents on retinal pigment epithelial (RPE) cells have been investigated, the effects of long-term and repeated treatment on these cells are scarce. In this study, we have investigated the effects of anti-VEGF treatment after long-term, repeated treatment on cell aging and morphology. The experiments were conducted in primary porcine RPE cells passage one and two...
March 6, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29454865/inhibitory-effects-of-selenium-on-cadmium-induced-cytotoxicity-in-pc12-cells-via-regulating-oxidative-stress-and-apoptosis
#12
Kaniz Fatima Binte Hossain, Md Mostafizur Rahman, Md Tajuddin Sikder, Takeshi Saito, Toshiyuki Hosokawa, Masaaki Kurasaki
Purpose of this study is to investigate mechanism/s of cyto-protection by selenium (Na2 SeO3 ; Se4+ ) against cadmium (CdCl2 ; Cd2+ )-induced cytotoxicity using PC12 cells. In addition, Se (5, 10, 20 and 40 μM) and Cd (2.5, 5 and 10 μM)-induced cytotoxicity is determined. Cytotoxicity assays and western blot analyses confirmed that Se (≥10 μM) promotes autophagic cell death via inhibition of mTOR activation and p62 accumulation due to increase of cellular oxidative stress. On the other hand, co-presence of non-toxic Se (5 μM) and toxic Cd (5 μM) showed to increase cell viability, glutathione and glutathione peroxidase 1 (GPx1) levels, and to decrease DNA fragmentation and lactate dehydrogenase (LDH) activity compared to Cd-treated (5 μM) cells alone...
February 15, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29420962/activation-of-serine-one-carbon-metabolism-by-calcineurin-a%C3%AE-1-reduces-myocardial-hypertrophy-and-improves-ventricular-function
#13
Laura Padrón-Barthe, María Villalba-Orero, Jesús M Gómez-Salinero, Rebeca Acín-Pérez, Sara Cogliati, Marina López-Olañeta, Paula Ortiz-Sánchez, Elena Bonzón-Kulichenko, Jesús Vázquez, Pablo García-Pavía, Nadia Rosenthal, José Antonio Enríquez, Enrique Lara-Pezzi
BACKGROUND: In response to pressure overload, the heart develops ventricular hypertrophy that progressively decompensates and leads to heart failure. This pathological hypertrophy is mediated, among others, by the phosphatase calcineurin and is characterized by metabolic changes that impair energy production by mitochondria. OBJECTIVES: The authors aimed to determine the role of the calcineurin splicing variant CnAβ1 in the context of cardiac hypertrophy and its mechanism of action...
February 13, 2018: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29415881/tak1-regulates-skeletal-muscle-mass-and-mitochondrial-function
#14
Sajedah M Hindi, Shuichi Sato, Guangyan Xiong, Kyle R Bohnert, Andrew A Gibb, Yann S Gallot, Joseph D McMillan, Bradford G Hill, Shizuka Uchida, Ashok Kumar
Skeletal muscle mass is regulated by a complex array of signaling pathways. TGF-β-activated kinase 1 (TAK1) is an important signaling protein, which regulates context-dependent activation of multiple intracellular pathways. However, the role of TAK1 in the regulation of skeletal muscle mass remains unknown. Here, we report that inducible inactivation of TAK1 causes severe muscle wasting, leading to kyphosis, in both young and adult mice.. Inactivation of TAK1 inhibits protein synthesis and induces proteolysis, potentially through upregulating the activity of the ubiquitin-proteasome system and autophagy...
February 8, 2018: JCI Insight
https://www.readbyqxmd.com/read/29386287/rsv-replication-is-promoted-by-autophagy-mediated-inhibition-of-apoptosis
#15
Miao Li, Jian Li, Jianling Yang, Jianguo Liu, Zhengzheng Zhang, Xiaotian Song, Zhiyan Yao, Cuiqing Ma, Wenjian Li, Ruihong Zeng, Kai Wang, Lin Wei
Respiratory syncytial virus (RSV) is the main cause of acute lower respiratory tract infection (ALRI) in children worldwide. Virus-host interaction affects progression and prognosis of the infection. Autophagy plays important roles in virus-host interaction. Respiratory epithelial cells serve as the front line of host defense during RSV infection, However, it is still unclear how they interact with RSV. In this study, We found that RSV induced autophagy which favored RSV replication and exacerbated lung pathology in vivo Mechanistically, RSV induced complete autophagy flux through Reactive oxygen species (ROS) generation and activation of AMPK-MTOR (AMP-activated protein kinase/mammalian target of rapamycin) signaling pathway in Hep2 cells...
January 31, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29378182/activation-of-mitochondrial-fusion-provides-a-new-treatment-for-mitochondria-related-diseases
#16
Aliz Szabo, Katalin Sumegi, Katalin Fekete, Eniko Hocsak, Balazs Debreceni, Gyorgy Setalo, Krisztina Kovacs, Laszlo Deres, Andras Kengyel, Dominika Kovacs, Jozsef Mandl, Miklos Nyitrai, Mark A Febbraio, Ferenc Gallyas, Balazs Sumegi
Mitochondria fragmentation destabilizes mitochondrial membranes, promotes oxidative stress and facilitates cell death, thereby contributing to the development and the progression of several mitochondria-related diseases. Accordingly, compounds that reverse mitochondrial fragmentation could have therapeutic potential in treating such diseases. BGP-15, a hydroxylamine derivative, prevents insulin resistance in humans and protects against several oxidative stress-related diseases in animal models. Here we show that BGP-15 promotes mitochondrial fusion by activating optic atrophy 1 (OPA1), a GTPase dynamin protein that assist fusion of the inner mitochondrial membranes...
January 26, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29353042/ginkgolic-acid-induces-interplay-between-apoptosis-and-autophagy-regulated-by-ros-generation-in-colon-cancer
#17
Yuxia Liu, Bin Yang, Lirong Zhang, Xianling Cong, Zhen Liu, Yu Hu, Jing Zhang, Haixia Hu
Presently, developing effective anti-colon cancer drugs still remains to be important. Ginkgolic acids (GA), as a botanical drug extracted from the seed coat of Ginkgo biloba L., possess various bioactive properties. Our findings, for the first time, indicated that GA suppressed colon cancer cell proliferation, migration and invasion. GA led to cell death through G0/G1 phase arrest. In addition, apoptosis was significantly induced by GA treatment. The intrinsic apoptosis pathway was included, proved by the release of cytochrome c (Cyto-c) from the mitochondria into the cytosol...
March 25, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29348263/phosphoinositide-3-kinase-gamma-inhibition-protects-from-anthracycline-cardiotoxicity-and-reduces-tumor-growth
#18
Mingchuan Li, Valentina Sala, Maria Chiara De Santis, James Cimino, Paola Cappello, Nicola Pianca, Anna Di Bona, Jean Piero Margaria, Miriam Martini, Edoardo Lazzarini, Flora Pirozzi, Luca Rossi, Irene Franco, Julia Bornbaum, Jacqueline Heger, Susanne Rohrbach, Alessia Perino, Carlo G Tocchetti, Braulio H F Lima, Mauro M Teixeira, Paolo E Porporato, Rainer Schulz, Annalisa Angelini, Marco Sandri, Pietro Ameri, Sebastiano Sciarretta, Roberto César P Lima-Júnior, Marco Mongillo, Tania Zaglia, Fulvio Morello, Francesco Novelli, Emilio Hirsch, Alessandra Ghigo
Background -Anthracyclines, such as doxorubicin (DOX), are potent anti-cancer agents for the treatment of solid tumors and hematological malignancies. However, their clinical use is hampered by cardiotoxicity. This study sought to investigate the role of PI3Kγ in DOX-induced cardiotoxicity and the potential cardio-protective and anti-cancer effects of PI3Kγ inhibition. Methods -Mice expressing a kinase-inactive PI3Kγ or receiving PI3Kγ selective inhibitors were subjected to chronic DOX treatment. Cardiac function was analyzed by echocardiography and DOX-mediated signaling was assessed in whole hearts or in isolated cardiomyocytes...
January 18, 2018: Circulation
https://www.readbyqxmd.com/read/29343514/trpm2-channel-mediated-regulation-of-autophagy-maintains-mitochondrial-function-and-promotes-gastric-cancer-cell-survival-via-the-jnk-signaling-pathway
#19
Shekoufeh Almasi, Barry E Kennedy, Mariam El Aghil, Andra M Sterea, Shashi Gujar, Santiago Partida-Sánchez, Yassine El Hiani
A lack of effective treatment is one of the main factors contributing to gastric cancer-related death. Discovering effective targets and understanding their underlying anticancer mechanism is key to achieving the best response to treatment and to limiting side effects. Although recent studies have shown that the cation channel transient receptor potential melastatin-2 (TRPM2) is crucial for cancer cell survival, the exact mechanism remains unclear, limiting its therapeutic potential. Here, using molecular and functional assays, we investigated the role of TRPM2 in survival of gastric cancer cells...
January 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29331805/synthesis-characterization-and-anticancer-activity-in-vitro-and-in-vivo-evaluation-of-an-iridium-iii-polypyridyl-complex
#20
Qiao-Yan Yi, Dan Wan, Bing Tang, Yang-Jie Wang, Wen-Yao Zhang, Fan Du, Miao He, Yun-Jun Liu
An iridium (III) complex [Ir(ppy)2 (BDPIP)]PF6 (Ir-1) was reported to show high anticancer activity and may be used as a potent anticancer drug. In the current study, we designed and synthesized a novel iridium (III) complex and evaluated its potential inhibitory effect on the cancer cell growth in vitro and in vivo. This complex was found to display high cytotoxic activity in vitro and in vivo against A549 cell with a low IC50 value of 3.6 ± 0.3 μM and inhibiting percentage of tumor growth is 63...
February 10, 2018: European Journal of Medicinal Chemistry
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