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Mitochondria AND mTOR

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https://www.readbyqxmd.com/read/28817179/autophagy-induction-plays-a-protective-role-against-hypoxic-stress-in-human-dental-pulp-cells
#1
Sam-Young Park, Eun-Gene Sun, Yeonju Lee, Min-Seok Kim, Jae Hyung Kim, Won-Jae Kim, Ji-Yeon Jung
Human dental pulp exposed to hypoxic conditions induces cell death accompanied by autophagy. However, the role of hypoxia-induced autophagy in human dental pulp cells (HDPCs) is unclear. The present study aimed to investigate the role of autophagy in hypoxia-induced apoptosis of HDPCs. Cobalt chloride (CoCl2 ) treated HDPCs, to mimic hypoxic conditions, decreased cell viability. Also, apoptosis-related signal molecules, cleaved caspase-3 and PARP levels, were enhanced in CoCl2 -treated HDPCs. HDPCs exposed to CoCl2 also promoted autophagy, showing upregulated p62 and microtubule-associated protein 1 light chain 3 (LC3)-II levels, typical autophagic markers, and increased acidic autophagolysosomal vacuoles...
August 17, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28807933/mice-deficient-in-lysophosphatidic-acid-acyltransferase-%C3%AE-lpaat%C3%AE-acylglycerophosphate-acyltransferase-4-agpat4-have-impairments-in-spatial-learning-and-memory-associated-with-reductions-in-nmda-and-ampa-receptors
#2
Ryan M Bradley, Emily B Mardian, Darin Bloemberg, Juan J Aristizabal Henao, Andrew S Mitchell, Phillip M Marvyn, Katherine A Moes, Ken D Stark, Joe Quadrilatero, Robin E Duncan
We previously characterized LPAATδ/AGPAT4 as a mitochondrial lysophosphatidic acid acyltransferase that regulates brain levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI). Here we report that Lpaatδ (-/-) mice display impaired spatial learning and memory compared to wildtype littermates in the Morris Water Maze, and investigated potential mechanisms associated with brain phospholipid changes. Marker protein immunoblotting suggested that the relative brain content of neurons, glia, and oligodendrocytes was unchanged...
August 14, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28804120/mitochondrial-energetics-in-the-kidney
#3
REVIEW
Pallavi Bhargava, Rick G Schnellmann
The kidney requires a large number of mitochondria to remove waste from the blood and regulate fluid and electrolyte balance. Mitochondria provide the energy to drive these important functions and can adapt to different metabolic conditions through a number of signalling pathways (for example, mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) pathways) that activate the transcriptional co-activator peroxisome proliferator-activated receptor-γ co-activator 1α (PGC1α), and by balancing mitochondrial dynamics and energetics to maintain mitochondrial homeostasis...
August 14, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28801921/autophagy-impairment-by-caspase-1-dependent-inflammation-mediates-memory-loss-in-response-to-%C3%AE-amyloid-peptide-accumulation
#4
Lourdes Álvarez-Arellano, Martha Pedraza-Escalona, Tonali Blanco-Ayala, Nohemí Camacho-Concha, Javier Cortés-Mendoza, Leonor Pérez-Martínez, Gustavo Pedraza-Alva
β-Amyloid peptide accumulation in the cortex and in the hippocampus results in neurodegeneration and memory loss. Recently, it became evident that the inflammatory response triggered by β-Amyloid peptides promotes neuronal cell death and degeneration. In addition to inflammation, β-Amyloid peptides also induce alterations in neuronal autophagy, eventually leading to neuronal cell death. Thus, here we evaluated whether the inflammatory response induced by the β-Amyloid peptides impairs memory via disrupting the autophagic flux...
August 12, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28718972/enhancement-of-mtor-signaling-contributes-to-acquired-x-ray-and-c-ion-resistance-in-mouse-squamous-carcinoma-cell-line
#5
Katsutoshi Sato, Rikako Azuma, Takashi Imai, Takashi Shimokawa
Our aim was to evaluate whether repetition of C-ion (carbon ion beam) irradiation induces radioresistance as well as repeated X-ray irradiation in cancer cell lines, and to find the key molecular pathway for radioresistance by comparing radioresistant cancer cells with their parental cells. A mouse squamous cell carcinoma cell line, NR-S1, and radioresistant cancer cells, NR-S1-C30 (C30) and NR-S1-X60 (X60) established by repetition of C-ion and X-ray irradiation respectively, were used. X-ray and C-ion sensitivity, changes in lysosome, mitochondria, intracellular ATP and ROS (reactive oxygen species) level, and mTOR (mechanistic target of rapamycin) signaling were evaluated...
July 18, 2017: Cancer Science
https://www.readbyqxmd.com/read/28696211/rab8a-deficiency-in-skeletal-muscle-causes-hyperlipidemia-and-hepatosteatosis-via-impairment-of-muscle-lipid-uptake-and-storage
#6
Qiaoli Chen, Ping Rong, Dijin Xu, Sangsang Zhu, Liang Chen, Bingxian Xie, Qian Du, Chao Quan, Yang Sheng, Tong-Jin Zhao, Peng Li, Hong Yu Wang, Shuai Chen
Skeletal muscle absorbs long chain fatty acids (LCFA) that are either oxidized in mitochondria or temporarily stored as triglycerides in lipid droplets (LDs). So far, it is still not fully understood how muscle lipid uptake and storage is regulated and whether it is important for whole-body lipid homeostasis. Here we show that the small GTPase Rab8a regulates muscle lipid uptake and storage in skeletal muscle. Muscle-specific Rab8a deletion caused hyperlipidemia and exacerbated high fat diet (HFD)-induced hepatosteatosis...
July 10, 2017: Diabetes
https://www.readbyqxmd.com/read/28673807/walsuronoid-b-induces-mitochondrial-and-lysosomal-dysfunction-leading-to-apoptotic-rather-than-autophagic-cell-death-via-ros-p53-signaling-pathways-in-liver-cancer
#7
Ya-di Geng, Chao Zhang, Jian-Li Lei, Pei Yu, Yuan-Zheng Xia, Hao Zhang, Lei Yang, Ling-Yi Kong
Walsuronoid B is a limonoid compound extracted from Walsura robusta. Previous studies have shown that limonoid compounds possess anti-cancer potential, although the molecular mechanism of this activity remains elusive. In this study, we demonstrated for the first time that walsuronoid B inhibited cell proliferation in several human cancer lines. Liver cancer cells (HepG2 and Bel-7402) were chosen for their high sensitivity to walsuronoid B. Walsuronoid B induced cell death through G2/M phase arrest and apoptosis and induced the accumulation of autophagosomes through the suppression of mTOR signaling, which serves as a cell survival mechanism and prevents cell death...
June 30, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28653223/multi-targeted-therapy-of-everolimus-in-kaposi-s-sarcoma-associated-herpes-virus-infected-primary-effusion-lymphoma
#8
Suchitra Mohanty, Amit Kumar, Piyanki Das, Sushil Kumar Sahu, Tathagata Choudhuri
Kaposi's sarcoma associated herpes virus (KSHV) infected primary effusion lymphoma (PEL) is a rare aggressive form of non-Hodgkin's lymphoma of B cells. KSHV latent and lytic antigens modulate several host cellular signalling pathways especially mammalian target of rapamycin (mTOR), STAT-3 and nuclear factor-kappa B (NF-κB) for rapid tumor progression and immune evasion. Current chemotherapeutic strategies are becoming ineffective as they kill only dividing cells and inefficient to target molecular pathways crucial for active virus replication and its survival...
June 26, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28619690/metformin-the-aspirin-of-the-21st-century-its%C3%A2-role-in-gestational-diabetes-mellitus-prevention-of-preeclampsia-and-cancer-and%C3%A2-the-promotion-of-longevity
#9
REVIEW
Roberto Romero, Offer Erez, Maik Hüttemann, Eli Maymon, Bogdan Panaitescu, Agustin Conde-Agudelo, Percy Pacora, Bo Hyun Yoon, Lawrence I Grossman
Metformin is everywhere. Originally introduced in clinical practice as an antidiabetic agent, its role as a therapeutic agent is expanding to include treatment of prediabetes mellitus, gestational diabetes mellitus, and polycystic ovarian disease and, more recently, experimental studies and observations in randomized clinical trials suggest that metformin could have a place in the treatment or prevention of preeclampsia. This article provides a brief overview of the history of metformin in the treatment of diabetes mellitus, reviews the results of metaanalyses of metformin in gestational diabetes mellitus, and the treatment of obese non-diabetic pregnant women to prevent macrosomia...
June 12, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28609310/blockade-of-glut1-by-wzb117-resensitizes-breast-cancer-cells-to-adriamycin
#10
Qing Chen, Ya-Qiu Meng, Xiao-Fan Xu, Jun Gu
The tolerance to adriamycin of cancer as a common and stubborn obstacle occurred during curing breast cancer patients needs to be overcome. In the present study, we explored whether inhibiting the glucose transporter 1 (GLUT1) could restore the activity of adriamycin in breast cancer cell line MCF-7 resistant to adriamycin and the possible underlying mechanisms. Adriamycin-resistant cell line MCF-7/ADR was selected stepwise from the parental MCF-7 cells and the level of GLUT1 was measured. Then, the MCF-7/ADR cells were incubated with adriamycin, WZB117 (a specific GLUT1 inhibitor), or both...
September 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28588226/the-effects-of-brazilian-green-propolis-that-contains-flavonols-against-mutant-copper-zinc-superoxide-dismutase-mediated-toxicity
#11
Tomoyuki Ueda, Masatoshi Inden, Katsuhiro Shirai, Shin-Ichiro Sekine, Yuji Masaki, Hisaka Kurita, Kenji Ichihara, Takashi Inuzuka, Isao Hozumi
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the selective and progressive loss of motor neurons. The purpose of this study was to clarify effects of brazilian green propolis and the active ingredient against ALS-associated mutant copper-zinc superoxide dismutase (SOD1)-mediated toxicity. Ethanol extract of brazilian green propolis (EBGP) protected N2a cells against mutant SOD1-induced neurotoxicity and reduced aggregated mutant SOD1 by induction of autophagy. Kaempferide and kaempferol, the active ingredients of EBGP, also inhibited mutant SOD1-induced cell death and reduced the intracellular mutant SOD1 aggregates...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28569781/mitochondrial-akap1-supports-mtor-pathway-and-tumor-growth
#12
Laura Rinaldi, Maria Sepe, Rossella Delle Donne, Kristel Conte, Antonietta Arcella, Domenica Borzacchiello, Stefano Amente, Fernanda De Vita, Monia Porpora, Corrado Garbi, Maria A Oliva, Claudio Procaccini, Deriggio Faicchia, Giuseppe Matarese, Federica Zito Marino, Gaetano Rocco, Sara Pignatiello, Renato Franco, Luigi Insabato, Barbara Majello, Antonio Feliciello
Mitochondria are the powerhouses of energy production and the sites where metabolic pathway and survival signals integrate and focus, promoting adaptive responses to hormone stimulation and nutrient availability. Increasing evidence suggests that mitochondrial bioenergetics, metabolism and signaling are linked to tumorigenesis. AKAP1 scaffolding protein integrates cAMP and src signaling on mitochondria, regulating organelle biogenesis, oxidative metabolism and cell survival. Here, we provide evidence that AKAP1 is a transcriptional target of Myc and supports the growth of cancer cells...
June 1, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28512260/targeting-metabolism-and-amp-activated-kinase-with-metformin-to-sensitize-non-small-cell-lung-cancer-nsclc-to-cytotoxic-therapy-translational-biology-and-rationale-for-current-clinical-trials
#13
REVIEW
Michael Troncone, Stephanie M Cargnelli, Linda A Villani, Naghmeh Isfahanian, Lindsay A Broadfield, Laura Zychla, Jim Wright, Gregory Pond, Gregory R Steinberg, Theodoros Tsakiridis
Lung cancer is the most fatal malignancy worldwide, in part, due to high resistance to cytotoxic therapy. There is need for effective chemo-radio-sensitizers in lung cancer. In recent years, we began to understand the modulation of metabolism in cancer and its importance in tumor progression and survival after cytotoxic therapy. The activity of biosynthetic pathways, driven by the Growth Factor Receptor/Ras/PI3k/Akt/mTOR pathway, is balanced by the energy stress sensor pathway of LKB1/AMPK/p53. AMPK responds both to metabolic and genotoxic stress...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28499984/systemic-pten-akt1-mtor-pathway-activity-in-patients-with-normal-tension-glaucoma-and-ocular-hypertension-a-case-series
#14
Gerassimos Lascaratos, Kai-Yin Chau, Haogang Zhu, Despoina Gkotsi, Deborah Kamal, Ivan Gout, Philip J Luthert, Anthony H V Schapira, David F Garway-Heath
Glaucoma is the most common optic neuropathy in humans and the leading cause of irreversible blindness worldwide. Its prevalence and incidence increase exponentially with ageing and raised intraocular pressure (IOP), while increasing evidence suggests that systemic mitochondrial abnormalities may also be implicated in its pathogenesis. We have recently shown that patients who have not developed glaucoma despite being exposed for many years to high IOP (ocular hypertension - OHT) have more efficient mitochondria, measured in peripheral blood lymphocytes, when compared to age-similar controls and fast progressing normal tension glaucoma (NTG) patients...
May 9, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28494869/mitochondrial-ros-production-protects-the-intestine-from-inflammation-through-functional-m2-macrophage-polarization
#15
Laura Formentini, Fulvio Santacatterina, Cristina Núñez de Arenas, Konstantinos Stamatakis, David López-Martínez, Angela Logan, Manuel Fresno, Ron Smits, Michael P Murphy, José M Cuezva
Mitochondria are signaling hubs in cellular physiology that play a role in inflammatory diseases. We found that partial inhibition of the mitochondrial ATP synthase in the intestine of transgenic mice triggers an anti-inflammatory response through NFκB activation mediated by mitochondrial mtROS. This shielding phenotype is revealed when mice are challenged by DSS-induced colitis, which, in control animals, triggers inflammation, recruitment of M1 pro-inflammatory macrophages, and the activation of the pro-oncogenic STAT3 and Akt/mTOR pathways...
May 9, 2017: Cell Reports
https://www.readbyqxmd.com/read/28476678/anticancer-efficacy-of-the-ethyl-acetate-extract-from-the-traditional-chinese-medicine-herb-celastrus-orbiculatus-against-human-gastric-cancer
#16
Haibo Wang, Lide Tao, Tengyang Ni, Hao Gu, Feng Jin, Xiaojun Dai, Jun Feng, Yanbing Ding, Weiming Xiao, Shiyu Guo, Tadashi Hisamitsu, Yayun Qian, Yanqing Liu
ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine (TCM) herb Celastrus orbiculatus is an important folk medicinal plant in China that has been used as an anti-inflammatory, antitumor, and analgesic in various diseases. The ethyl acetate extract of C. orbiculatus (C. orbiculatus extract, COE) was reported to show significant antitumor effects. However, no study in China or abroad has reported the effect and mechanism of COE in triggering apoptosis of gastric cancer (GC) cells...
May 2, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28473584/anti-inflammatory-effect-of-il-10-mediated-by-metabolic-reprogramming-of-macrophages
#17
W K Eddie Ip, Namiko Hoshi, Dror S Shouval, Scott Snapper, Ruslan Medzhitov
Interleukin 10 (IL-10) is an anti-inflammatory cytokine that plays a critical role in the control of immune responses. However, its mechanisms of action remain poorly understood. Here, we show that IL-10 opposes the switch to the metabolic program induced by inflammatory stimuli in macrophages. Specifically, we show that IL-10 inhibits lipopolysaccharide-induced glucose uptake and glycolysis and promotes oxidative phosphorylation. Furthermore, IL-10 suppresses mammalian target of rapamycin (mTOR) activity through the induction of an mTOR inhibitor, DDIT4...
May 5, 2017: Science
https://www.readbyqxmd.com/read/28469639/telomerase-and-mtor-in-the-brain-the-mitochondria-connection
#18
REVIEW
Satomi Miwa, Gabriele Saretzki
Telomerase is an enzyme that maintains telomeres in dividing cells using a template on its inherent RNA component. Additionally, the protein part TERT (Telomerase Reverse Transcriptase) has various non-canonical functions. For example, it can localize to mitochondria under increased stress and protect cells in vitro from oxidative stress, DNA damage and apoptosis. Recently it has been demonstrated that TERT protein persists in adult neurons in the brain and data emerge suggesting that it might have a protective function in these post-mitotic cells as well...
March 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28433710/down-regulation-of-islet-amyloid-polypeptide-expression-induces-death-of-human-annulus-fibrosus-cells-via-mitochondrial-and-death-receptor-pathways
#19
Xinghuo Wu, Kun Wang, Wenbin Hua, Shuai Li, Xianzhe Liu, Wei Liu, Yu Song, Yukun Zhang, Zengwu Shao, Cao Yang
Islet amyloid polypeptide (IAPP) exerts its biological effects by participating in the regulation of glucose metabolism and cell apoptosis. The main goal of the present study was to investigate the expression of IAPP in degenerated intervertebral disc tissue and IAPP's modulation of extracellular matrix (ECM) catabolic and anabolic genes in human AF cells. We found that the expression of IAPP, the calcitonin receptor, and receptor activity modifying protein decreased considerably in AF cells during the progression of intervertebral disc degeneration (IDD)...
April 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28428083/the-roles-of-subcellularly-located-egfr-in-autophagy
#20
REVIEW
Hongsen Li, Liangkun You, Jiansheng Xie, Hongming Pan, Weidong Han
The epidermal growth factor receptor (EGFR) is a well-studied receptor-tyrosine kinase that serves vital roles in regulation of organ development and cancer progression. EGFR not only exists on the plasma membrane, but also widely expressed in the nucleus, endosomes, and mitochondria. Most recently, several lines of evidences indicated that autophagy is regulated by EGFR in kinase-active and -independent manners. In this review, we summarized recent advances in our understanding of the functions of different subcellularly located EGFR on autophagy...
April 18, 2017: Cellular Signalling
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