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https://www.readbyqxmd.com/read/29792365/protective-effects-of-piceatannol-on-methylglyoxal-induced-cytotoxicity-in-mc3t3-e1-osteoblastic-cells
#1
Kwang Sik Suh, Suk Chon, Eun Mi Choi
Methylglyoxal (MG) is a reactive α-oxoaldehyde that increases under diabetic conditions and subsequently contributes to the complications associated with this disease. Piceatannol is a naturally occurring analogue of resveratrol that possesses multiple biological functions. The present study investigated the effects of piceatannol on MG-induced cytotoxicity in MC3T3-E1 osteoblastic cells. Piceatannol significantly restored MG-induced reductions in cell viability and reduced lactate dehydrogenase release in MG-treated MC3T3-E1 osteoblastic cells, which suggests that it suppressed MG-induced cytotoxicity...
June 2018: Free Radical Research
https://www.readbyqxmd.com/read/29791858/a-multi-layered-quantitative-in-vivo-expression-atlas-of-the-podocyte-unravels-kidney-disease-candidate-genes
#2
Markus M Rinschen, Markus Gödel, Florian Grahammer, Stefan Zschiedrich, Martin Helmstädter, Oliver Kretz, Mostafa Zarei, Daniela A Braun, Sebastian Dittrich, Caroline Pahmeyer, Patricia Schroder, Carolin Teetzen, HeonYung Gee, Ghaleb Daouk, Martin Pohl, Elisa Kuhn, Bernhard Schermer, Victoria Küttner, Melanie Boerries, Hauke Busch, Mario Schiffer, Carsten Bergmann, Marcus Krüger, Friedhelm Hildebrandt, Joern Dengjel, Thomas Benzing, Tobias B Huber
Damage to and loss of glomerular podocytes has been identified as the culprit lesion in progressive kidney diseases. Here, we combine mass spectrometry-based proteomics with mRNA sequencing, bioinformatics, and hypothesis-driven studies to provide a comprehensive and quantitative map of mammalian podocytes that identifies unanticipated signaling pathways. Comparison of the in vivo datasets with proteomics data from podocyte cell cultures showed a limited value of available cell culture models. Moreover, in vivo stable isotope labeling by amino acids uncovered surprisingly rapid synthesis of mitochondrial proteins under steady-state conditions that was perturbed under autophagy-deficient, disease-susceptible conditions...
May 22, 2018: Cell Reports
https://www.readbyqxmd.com/read/29791786/matrine-suppresses-kras-driven-pancreatic-cancer-growth-by-inhibiting-autophagy-mediated-energy-metabolism
#3
Young-Ra Cho, Ji Hyeon Lee, Ji Hye Kim, So-Yeon Lee, Suna Yoo, Min-Kyo Jung, Su Jung Kim, Hyun Ju Yoo, Chang-Gi Pack, Jin Kyung Rho, Jaekyoung Son
Matrine is a natural compound extracted from the herb Sophora flavescens Ait which is widely used in traditional Chinese medicine for treating various diseases. Recently, matrine was reported to have antitumor effects against a variety of cancers without any obvious side effects; however, the molecular mechanisms of its antiproliferative effects on cancer are unclear. Here, we report that matrine inhibits autophagy-mediated energy metabolism, which is necessary for pancreatic cancer growth. We found that matrine significantly reduces pancreatic cancer growth in vitro and in vivo by insufficiently maintaining mitochondrial metabolic function and energy level...
May 23, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29789637/the-proton-pump-inhibitor-pantoprazole-disrupts-protein-degradation-systems-and-sensitizes-cancer-cells-to-death-under-various-stresses
#4
Yu Cao, Min Chen, Dehua Tang, Hongli Yan, Xiwei Ding, Fan Zhou, Mingming Zhang, Guifang Xu, Weijie Zhang, Shu Zhang, Yuzheng Zhuge, Lei Wang, Xiaoping Zou
Proton pump inhibitors (PPIs) play a role in antitumor activity, with studies showing specialized impacts of PPIs on cancer cell apoptosis, metastasis, and autophagy. In this study, we demonstrated that pantoprazole (PPI) increased autophagosomes formation and affected autophagic flux depending on the pH conditions. PPI specifically elevated SQSTM1 protein levels by increasing SQSTM1 transcription via NFE2L2 activation independent of the specific effect of PPI on autophagic flux. Via decreasing proteasome subunits expression, PPI significantly impaired the function of the proteasome, accompanied by the accumulation of undegraded poly-ubiquitinated proteins...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29789603/vorinostat-and-quinacrine-have-synergistic-effects-in-t-cell-acute-lymphoblastic-leukemia-through-reactive-oxygen-species-increase-and-mitophagy-inhibition
#5
Bo Jing, Jin Jin, Rufang Xiang, Meng Liu, Li Yang, Yin Tong, Xinhua Xiao, Hu Lei, Wei Liu, Hanzhang Xu, Jiong Deng, Li Zhou, Yingli Wu
Despite recent progress in the treatment, the outcome of adult acute T-cell lymphoblastic leukemia (T-ALL) is poor. Development of novel approach to combat this disease is urgently required. Vorinostat, a pan-histone deacetylase (HDAC) inhibitor, exerts promising anticancer activity in a variety of solid and hematologic malignancies. However, the efficacy of vorinostat monotherapy is unsatisfactory. Here, we show that quinacrine (QC), an anti-malaria drug with potent autophagy inhibitory activity, could synergistically enhance vorinostat-induced cell death at a non-toxic concentration...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29788929/resveratrol-induces-autophagy-dependent-apoptosis-in-hl-60-cells
#6
Yingying Fan, Jen-Fu Chiu, Jing Liu, Yan Deng, Cheng Xu, Jun Zhang, Guanwu Li
BACKGROUND: All known mechanisms of apoptosis induced by resveratrol act through cell cycle arrest and changes in mitochondrial membrane potential. It is currently unknown whether resveratrol-induced apoptosis is associated with other physiological processes, such as autophagy. METHODS: Apoptosis-related markers involved in the intrinsic and extrinsic apoptotic pathways, and autophagic markers were detected by using western blotting and immunofluorescence. Mitochondrial membrane potential was assayed by flow cytometry...
May 22, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29787763/the-torc1-signaling-pathway-regulates-respiration-induced-mitophagy-in-yeast
#7
Yang Liu, Koji Okamoto
Mitophagy is an evolutionarily conserved autophagy process that selectively degrades mitochondria. This catabolic event is considered to be a mitochondrial quality control system crucial for cell homeostasis, however, mechanisms regulating mitophagy remain largely unknown. Here we show that the TORC1 (target of rapamycin complex 1) signaling pathway regulates mitophagy in budding yeast via SEACIT (Seh1-associated complex inhibiting TORC1) consisting of Iml1, Npr2, and Npr3. Cells lacking SEACIT displayed significant reductions in mitophagy during prolonged respiratory growth, while the other selective autophagy processes are less affected...
May 19, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29785242/role-of-oxidative-stress-as-key-regulator-of-muscle-wasting-during-cachexia
#8
REVIEW
Johanna Ábrigo, Alvaro A Elorza, Claudia A Riedel, Cristian Vilos, Felipe Simon, Daniel Cabrera, Lisbell Estrada, Claudio Cabello-Verrugio
Skeletal muscle atrophy is a pathological condition mainly characterized by a loss of muscular mass and the contractile capacity of the skeletal muscle as a consequence of muscular weakness and decreased force generation. Cachexia is defined as a pathological condition secondary to illness characterized by the progressive loss of muscle mass with or without loss of fat mass and with concomitant diminution of muscle strength. The molecular mechanisms involved in cachexia include oxidative stress, protein synthesis/degradation imbalance, autophagy deregulation, increased myonuclear apoptosis, and mitochondrial dysfunction...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29784660/interleukin-6-reduces-%C3%AE-cell-oxidative-stress-by-linking-autophagy-with-the-antioxidant-response
#9
Michelle R Marasco, Abass M Conteh, Christopher A Reissaus, John E Cupit V, Evan M Appleman, Raghavendra G Mirmira, Amelia K Linnemann
Production of reactive oxygen species (ROS) is a key instigator of β-cell dysfunction in diabetes. The pleiotropic cytokine IL-6 has previously been linked to β-cell autophagy but has not been studied in the context of β-cell antioxidant response. We used a combination of animal models of diabetes and analysis of cultured human islets and rodent β-cells to study how IL-6 influences antioxidant response. We show that IL-6 couples autophagy to antioxidant response to reduce β-cell and human islet ROS. β cell-specific loss of IL-6 signaling in vivo renders mice more susceptible to oxidative damage and cell death by the selective β-cell toxins streptozotocin and alloxan...
May 21, 2018: Diabetes
https://www.readbyqxmd.com/read/29782848/impaired-tfeb-mediated-lysosome-biogenesis-and-autophagy-promote-chronic-ethanol-induced-liver-injury-and-steatosis-in-mice
#10
Xiaojuan Chao, Shaogui Wang, Katrina Zhao, Yuan Li, Jessica A Williams, Tiangang Li, Hemantkumar Chavan, Partha Krishnamurthy, Xi C He, Linheng Li, Andrea Ballabio, Hong-Min Ni, Wen-Xing Ding
BACKGROUND & AIMS: Defects in lysosome function and autophagy contribute to pathogenesis of alcoholic liver disease. We investigated the mechanisms by which alcohol consumption affects these processes, evaluating the functions transcription factor EB (TFEB), which regulates lysosomal biogenesis. METHODS: We performed studies with GFP-LC3 mice, mice with liver-specific deletion of transcription factor EB (TFEB), mice with disruption of the transcription factor E3 gene (TFE3-knockout mice), mice with disruption of the Tefb and Tfe3 genes (TFEB, TFE3 double-knockout mice), and Tfebflox/flox albumin cre-negative mice (controls)...
May 18, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29781176/autophagy-and-mitophagy-flux-in-young-and-aged-skeletal-muscle-following-chronic-contractile-activity
#11
Heather N Carter, Yuho Kim, Avi T Erlich, Dorrin Zarrin-Khat, David A Hood
Skeletal muscle exhibits deficits in mitochondrial quality with age. Central to the maintenance of a healthy mitochondrial pool is the removal of dysfunctional organelles via mitophagy. Little is known on how mitophagy is altered with aging and chronic exercise. We assessed mitophagy flux using colchicine treatment in vivo following chronic contractile activity (CCA) of muscle in young and aged rats. CCA evoked mitochondrial biogenesis in young muscle, with an attenuated response in aged muscle. Mitophagy flux was higher in aged muscle and was correlated with the enhanced expression of mitophagy receptors and upstream transcriptional regulators...
May 20, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29778937/copper-ii-and-or-arsenite-induced-oxidative-stress-cascades-apoptosis-and-autophagy-in-the-skeletal-muscles-of-chicken
#12
Yu Wang, Hongjing Zhao, Yizhi Shao, Juanjuan Liu, Jinglun Li, Liyang Luo, Mingwei Xing
Arsenic (As) is a ubiquitous environmental toxin and robust inducer of oxidative stress (OxS). Copper (Cu) is an essential microelement, which participates in OxS as a cofactor for certain enzymes, with narrow optimal range between essential and toxic concentrations. However, their effects are rarely studied in chicken skeletal muscles, which have soaring per capita consumption andare susceptible to oxidative damage. In the present study, we demonstrated that the administration of copper sulfate (300 mg kg-1 ) or arsenite (30 mg kg-1 ) individually or their co-administration leads to varying degrees of OxS in the skeletal muscles of chickens...
May 11, 2018: Chemosphere
https://www.readbyqxmd.com/read/29778718/nimbolide-epigenetically-regulates-autophagy-and-apoptosis-in-breast-cancer
#13
Venkatesh Pooladanda, Soumya Bandi, Sandhya Rani Mondi, Krishna Mohan Gottumukkala, Chandraiah Godugu
Autophagy is a critical regulator of cellular homeostasis and its dysregulation often results in various disease manifestations, including cancer. Nimbolide, an active chemical constituent of neem (Azadirachta indica) exhibits potent anticancer effects. Although, nimbolide mediated apoptosis activation in breast cancer cells is well known. Nevertheless, its role in autophagy induction mechanism and epigenetic alteration is not explored previously. Our current study intended to bridge the gaps in the existing research by exploring the potential of nimbolide in inducing autophagy, which could counter regulate the transformations in breast cancer...
May 17, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29777261/mitochondrial-quality-control-in-amd-does-mitophagy-play-a-pivotal-role
#14
REVIEW
Juha M T Hyttinen, Johanna Viiri, Kai Kaarniranta, Janusz Błasiak
Age-related macular degeneration (AMD) is the predominant cause of visual loss in old people in the developed world, whose incidence is increasing. This disease is caused by the decrease in macular function, due to the degeneration of retinal pigment epithelium (RPE) cells. The aged retina is characterised by increased levels of reactive oxygen species (ROS), impaired autophagy, and DNA damage that are linked to AMD pathogenesis. Mitophagy, a mitochondria-specific type of autophagy, is an essential part of mitochondrial quality control, the collective mechanism responsible for this organelle's homeostasis...
May 18, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29777200/a-map-of-the-pgc-1%C3%AE-and-nt-pgc-1%C3%AE-regulated-transcriptional-network-in-brown-adipose-tissue
#15
Ji Suk Chang, Sujoy Ghosh, Susan Newman, J Michael Salbaum
Transcriptional coactivator PGC-1α and its splice variant NT-PGC-1α play crucial roles in regulating cold-induced thermogenesis in brown adipose tissue (BAT). PGC-1α and NT-PGC-1α are highly induced by cold in BAT and subsequently bind to and coactivate many transcription factors to regulate expression of genes involved in mitochondrial biogenesis, fatty acid oxidation, respiration and thermogenesis. To identify the complete repertoire of PGC-1α and NT-PGC-1α target genes in BAT, we analyzed genome-wide DNA-binding and gene expression profiles...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29774638/loss-of-sirtuin-1-and-mitofusin-2-contributes-to-enhanced-ischemia-reperfusion-injury-in-aged-livers
#16
Sung Kook Chun, Sooyeon Lee, Joseph Flores-Toro, Rebecca Y U, Ming-Jim Yang, Kristina L Go, Thomas G Biel, Catherine E Miney, Schiley Pierre Louis, Brian K Law, Mary E Law, Elizabeth M Thomas, Kevin E Behrns, Christiaan Leeuwenburgh, Jae-Sung Kim
Ischemia/reperfusion (I/R) injury is a causative factor contributing to morbidity and mortality during liver resection and transplantation. Livers from elderly patients have a poorer recovery from these surgeries, indicating reduced reparative capacity with aging. Mechanisms underlying this age-mediated hypersensitivity to I/R injury remain poorly understood. Here, we investigated how sirtuin 1 (SIRT1) and mitofusin 2 (MFN2) are affected by I/R in aged livers. Young (3 months) and old (23-26 months) male C57/BL6 mice were subjected to hepatic I/R in vivo...
May 17, 2018: Aging Cell
https://www.readbyqxmd.com/read/29770446/anticancer-activity-of-tetrandrine-by-inducing-pro-death-apoptosis-and-autophagy-in-human-gastric-cancer-cells
#17
Xin-Yu Bai, Yuan-Gui Liu, Wu Song, Ying-Ying Li, Dong-Shun Hou, Hao-Ming Luo, Ping Liu
OBJECTIVES: To investigate the antitumour property of tetrandrine by inducing autophagy and apoptosis in human gastric cancer cells, and to explore the potential molecular mechanisms. METHODS: The antitumour activity of tetrandrine was assessed through MTT assay. Apoptosis was measured by flow cytometry and microscopic examination of cellular morphology. The mitochondrial membrane potential was detected by staining with Rh-123. Induction of autophagy was monitored by transmission electron microscopy observation, using GFP-LC3 transfection...
May 16, 2018: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/29769325/the-ancient-phosphatidylinositol-3-kinase-signaling-system-is-a-master-regulator-of-energy-and-carbon-metabolism-in-algae
#18
Rishiram Ramanan, Quynh-Giao Tran, Dae-Hyun Cho, Jae-Eun Jeong, Byung-Hyuk Kim, Sang-Yoon Shin, Sae-Hae Choi, Kwang-Hyeon Liu, Dae-Soo Kim, Seon-Jin Lee, Jose L Crespo, Hee-Gu Lee, Hee-Mock Oh, Hee-Sik Kim
Algae undergo a complete metabolic transformation under stress by arresting cell growth, inducing autophagy, and hyper-accumulating biofuel precursors such as triacylglycerols and starch. However, the regulatory mechanisms behind this stress-induced transformation are still unclear. Here, we use biochemical, mutational, and 'omics' approaches to demonstrate that phosphatidylinositol 3-kinase (PI3K) signaling mediates the homeostasis of energy molecules and influences carbon metabolism in algae. In Chlamydomonas reinhardtii, the inhibition and knockdown (KD) of algal class III PI3K led to significantly decreased cell growth, altered cell morphology, and higher lipid and starch contents...
May 16, 2018: Plant Physiology
https://www.readbyqxmd.com/read/29768017/the-signaling-network-resulting-in-ventilator-induced-diaphragm-dysfunction
#19
Huibin Tang, Joseph B Shrager
Mechanical ventilation (MV) is a life-saving measure for those incapable of adequately ventilating or oxygenating without assistance. Unfortunately, even brief periods of MV result in diaphragm weakness (i.e., "ventilator-induced diaphragm dysfunction" - VIDD) that may render it difficult to wean the ventilator. Prolonged MV is associated with cascading complications and is a strong risk factor for death. Thus, prevention of VIDD may have a dramatic impact on mortality rates. Here, we summarized the current understanding of the pathogenic events underlying VIDD...
May 16, 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29765509/resveratrol-induced-downregulation-of-naf-1-enhances-the-sensitivity-of-pancreatic-cancer-cells-to-gemcitabine-via-the-ros-nrf2-signaling-pathways
#20
Liang Cheng, Bin Yan, Ke Chen, Zhengdong Jiang, Cancan Zhou, Junyu Cao, Weikun Qian, Jie Li, Liankang Sun, Jiguang Ma, Qingyong Ma, Huanchen Sha
NAF-1 (nutrient-deprivation autophagy factor-1), which is an outer mitochondrial membrane protein, is known to play important roles in calcium metabolism, antiapoptosis, and antiautophagy. Resveratrol, a natural polyphenolic compound, is considered as a potent anticancer agent. Nevertheless, the molecular mechanisms underlying the effects of resveratrol and NAF-1 and their mediation of drug resistance in pancreatic cancer remain unclear. Here, we demonstrate that resveratrol suppresses the expression of NAF-1 in pancreatic cancer cells by inducing cellular reactive oxygen species (ROS) accumulation and activating Nrf2 signaling...
2018: Oxidative Medicine and Cellular Longevity
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