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Wen Gu, Rong Cui, Tao Ding, Xiaoming Li, Juan Peng, Weiguo Xu, Fengfeng Han, Xuejun Guo
BACKGROUND AND OBJECTIVE: Statins have been widely used in inflammatory diseases including asthma, because of their anti-inflammatory and immunomodulatory properties. It has been shown that simvastatin induces autophagy and cell death in some circumstances. However, the possible cross-talk between simvastatin and autophagic processes in lung disease is largely unknown. Thus, we investigated the impact of simvastatin on airway inflammation and airway remodelling and the possible relationship of these processes to a simvastatin-induced autophagic pathway in mouse models of asthma...
October 26, 2016: Respirology: Official Journal of the Asian Pacific Society of Respirology
Haojie Sun, Mingzhi Zhang, Kai Cheng, Peng Li, Shuo Han, Ruizhi Li, Ming Su, Wotan Zeng, Jinwen Liu, Jinhai Guo, Yinan Liu, Xiaoyan Zhang, Qihua He, Li Shen
CD133 is a pentaspan transmembrane protein that can serve as a biomarker for cancer stem cells, although its biochemical mechanism remains unclear. Here we report that CD133 expression enhances glioma cell tolerance of a nutrient-deprived microenvironment. Under starvation conditions, CD133-positive cells exhibited higher survival and decreased levels of apoptosis. These changes were dependent on activation of autophagy-associated gene signaling and were impaired by the autophagic inhibitor chloroquine. Furthermore, rapamycin up-regulated the level of autophagy and inversely reduced CD133 expression...
October 21, 2016: Oncotarget
Jeong Su Park, Sue Young Oh, Da Hyun Lee, Yu Seol Lee, Su Haeng Sung, Hye Won Ji, Moon Joo Lee, Yong-Ho Lee, Sue Goo Rhee, Soo Han Bae
Endoplasmic reticulum (ER) stress is triggered by various cellular stresses that disturb protein folding or calcium homeostasis in the ER. To cope with these stresses, ER stress activates the unfolded protein response (UPR) pathway, but unresolved ER stress induces reactive oxygen species (ROS) accumulation leading to apoptotic cell death. However, the mechanisms that underlie protection from ER stress-induced cell death are not clearly defined. The nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway plays a crucial role in the protection of cells against ROS-mediated oxidative damage...
October 26, 2016: Free Radical Research
Qiang Fu, Jing Cheng, Jindai Zhang, Yonglei Zhang, Xiaobing Chen, Jianguo Xie, Suxia Luo
Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. Deregulation of microRNAs (miRNAs) has been reported to participate in CRC progression. In the present study, we observed downregulation of miR-218 and upregulation of YEATS domain containing 4 (YEATS4) in CRC tissues and in multidrug-resistant HCT-116/L-OHP cells compared with these levels in normal tissues and parental HCT-116 cells, respectively. The results indicated that miR-218 overexpression significantly decreased the IC50 value of oxaliplatin (L-OHP) in the HCT-116/L-OHP cells, and suppression of miR-218 significantly enhanced the IC50 of L-OHP in the HCT-116 cells...
October 21, 2016: Oncology Reports
Yong-Bo Li, Xiang-Ru Li, Ting Yang, Jin-Xing Wang, Xiao-Fan Zhao
Autophagy regulates cell survival (or cell death in several cases), whereas apoptosis regulates cell death. However, the relationship between autophagy and apoptosis and the regulative mechanism is unclear. We report that steroid hormone 20-hydroxyecdysone (20E) promotes switching from autophagy to apoptosis by increasing intracellular calcium levels in the midgut of the lepidopteran insect Helicoverpa armigera. Autophagy and apoptosis sequentially occurred during midgut programmed cell death under 20E regulation, in which lower concentrations of 20E induced microtubule-associated protein 1 light chain 3-phosphatidylethanolamine (LC3-II, also known as autophagy-related gene 8, ATG8) expression and autophagy...
October 21, 2016: Insect Biochemistry and Molecular Biology
Qianqian Dong, Wenjuan Xing, Feng Fu, Zhenghua Liu, Jie Wang, Xiangyan Liang, Xuanxuan Zhou, Qian Yang, Wei Zhang, Feng Gao, Siwang Wang, Haifeng Zhang
Autophagy exists in vascular endothelial cells, but the relationship between autophagy and blood vessel dysfunction in hypertension remains elusive. This study aimed to investigate role of autophagy in vascular endothelial dysfunction in prehypertension and hypertension and the underlying mechanisms involved. Furthermore, we sought to determine if and how tetrahydroxystilbene glucoside (TSG), a resveratrol analogue and active ingredient of Polygonum multiflorum Thunb used for its cardiovascular protective properties in traditional Chinese medicine, influences vascular endothelial function...
October 25, 2016: American Journal of Chinese Medicine
Gong-Jhe Wu, Chien-Ju Lin, Yung-Wei Lin, Ruei-Ming Chen
This article contains raw and processed data related to a research, "Honokiol induces autophagic cell death in malignant glioma through reactive oxygen species-mediated regulation of the p53/PI3K/Akt/mTOR signaling pathway" (C.J. Lin, T.L. Chen, Y.Y. Tseng, G.J. Wu, M.H. Hsieh, Y.W. Lin, R.M. Chen, 2016) [1]. Data were obtained by immunoblotting analyses of light chain 3 (LC3)-II, beclin-1, Akt, and mTOR in human glioma U87 MG cells and mouse glioma tissues treated with honokiol, an active constituent extracted from the bark of Magnolia officinalis, "Honokiol induces autophagy of neuroblastoma cells through activating the PI3K/Akt/mTOR and endoplasmic reticular stress/ERK1/2 signaling pathways and suppressing cell migration" (P...
December 2016: Data in Brief
Liliana F Iannucci, Jingfeng Sun, Brijesh K Singh, Jin Zhou, Vincent A Kaddai, Antonia Lanni, Paul M Yen, Rohit A Sinha
Short-chain fatty acids (SCFAs) are gut microbial fermentation products derived from dietary fiber sources. Although depletion of gut microflora has been linked to the development of liver disease, the direct effects of SCFAs on intracellular hepatic processes are not well understood. In this study, we demonstrated that the SCFAs, propionate and butyrate, regulated autophagic flux in hepatic cells in a cell-autonomous manner. Induction of autophagy by SCFAs required PPARγ stimulation of Uncoupling Protein 2 (UCP2) expression that was associated with reduced intracellular ATP levels and activation of PRKAA1/AMPK (protein kinase, AMP-activated, alpha 1 catalytic subunit)...
October 20, 2016: Biochemical and Biophysical Research Communications
Danielle Oliveira Dos Anjos, Eliomara Sousa Sobral Alves, Vinicius Tomaz Gonçalves, Sheila Suarez Fontes, Mateus Lima Nogueira, Ana Márcia Suarez-Fontes, João Batista Neves da Costa, Fabricio Rios-Santos, Marcos André Vannier-Santos
Natural products comprise valuable sources for new antiparasitic drugs. Here we tested the effects of a novel β-lapachone derivative on Trypanosoma cruzi parasite survival and proliferation and used microscopy and cytometry techniques to approach the mechanism(s) underlying parasite death. The selectivity index determination indicate that the compound trypanocidal activity was over ten-fold more cytotoxic to epimastigotes than to macrophages or splenocytes. Scanning electron microscopy analysis revealed that the R72 β-lapachone derivative affected the T...
October 12, 2016: International Journal for Parasitology, Drugs and Drug Resistance
Yinyan Xu, Xinyan Huang, Juan Xie, Yanni Chen, Jing Fu, Li Wang
Autophagy, identified as type II programmed cell death, has already been known to be involved in the pathophysiology of preeclampsia (PE), which is a gestational disease with high morbidity. The present study aims to investigate the functional role of let-7i, a miRNA, in trophoblastic autophagy. Placental tissue used in this study was collected from patients with severe preeclampsia (SPE) or normal pregnant women. A decreased level of let-7i was found in placenta of SPE. In addition, autophagic vacuoles were observed in SPE and the expression of microtubule associated protein 1 light chain 3 (LC3) II/I was elevated...
October 22, 2016: Journal of Cellular Physiology
Cheng-Fu Chang, Yi-Chao Lee, Kuen-Haur Lee, Hui-Ching Lin, Chia-Ling Chen, Che-Kun James Shen, Chi-Chen Huang
BACKGROUND: In the central nervous system regions of the sporadic and familial FTLD and ALS patients, TDP-43 has been identified as the major component of UBIs inclusions which is abnormally hyperphosphorylated, ubiquitinated, and cleaved into C-terminal fragments to form detergent-insoluble aggregates. So far, the effective drugs for FTLD and ALS neurodegenerative diseases are yet to be developed. Autophagy has been demonstrated as the major metabolism route of the pathological TDP-43 inclusions, hence activation of autophagy is a potential therapeutic strategy for TDP-43 pathogenesis in FTLD and ALS...
October 21, 2016: Journal of Biomedical Science
Massimo Nabissi, Maria Beatrice Morelli, Massimo Offidani, Consuelo Amantini, Silvia Gentili, Alessandra Soriani, Claudio Cardinali, Pietro Leoni, Giorgio Santoni
Several studies showed a potential anti-tumor role for cannabinoids, by modulating cell signaling pathways involved in cancer cell proliferation, chemo-resistance and migration. Cannabidiol (CBD) was previously noted in multiple myeloma (MM), both alone and in synergy with the proteasome inhibitor bortezomib, to induce cell death. In other type of human cancers, the combination of CBD with Δ9-tetrahydrocannabinol (THC) was found to act synergistically with other chemotherapeutic drugs suggesting their use in combination therapy...
October 18, 2016: Oncotarget
Raffaela Torggler, Daniel Papinski, Thorsten Brach, Levent Bas, Martina Schuschnig, Thaddäus Pfaffenwimmer, Sabrina Rohringer, Tamara Matzhold, David Schweida, Andrea Brezovich, Claudine Kraft
Autophagy is a potent cellular degradation pathway, and its activation needs to be tightly controlled. Cargo receptors mediate selectivity during autophagy by bringing cargo to the scaffold protein Atg11 and, in turn, to the autophagic machinery, including the central autophagy kinase Atg1. Here we show how selective autophagy is tightly regulated in space and time to prevent aberrant Atg1 kinase activation and autophagy induction. We established an induced bypass approach (iPass) that combines genetic deletion with chemically induced dimerization to evaluate the roles of Atg13 and cargo receptors in Atg1 kinase activation and selective autophagy progression...
October 20, 2016: Molecular Cell
Oznur Bayraktar, Ozlem Oral, Nur Mehpare Kocaturk, Yunus Akkoc, Karin Eberhart, Ali Kosar, Devrim Gozuacik
The ubiquitin-proteasome system (UPS) degrades soluble proteins and small aggregates, whereas macroautophagy (autophagy herein) eliminates larger protein aggregates, tangles and even whole organelles in a lysosome-dependent manner. VCP/p97 was implicated in both pathways. VCP/p97 mutations cause a rare multisystem disease called IBMPFD (Inclusion Body Myopathy with Paget's Disease and Frontotemporal Dementia). Here, we studied the role IBMPFD-related mutants of VCP/p97 in autophagy. In contrast with the wild-type VCP/p97 protein or R155C or R191Q mutants, the P137L mutant was aggregate-prone...
2016: PloS One
Joan Yw Liu, Cheryl Reeves, Beate Diehl, Antonietta Coppola, Aliya Al-Hajri, Chandrashekar Hoskote, Salim Al Mughairy, Mohamed Tachrount, Michael Groves, Zuzanna Michalak, Kevin Mills, Andrew W McEvoy, Anna Miserocchi, Sanjay M Sisodiya, Maria Thom
OBJECTIVE: This study reports on a novel brain pathology in young patients with Frontal Lobe Epilepsy that is distinct from Focal Cortical Dysplasia. METHODS: Surgical specimens from twenty young adults with frontal lobe epilepsy (mean age, 30 years) were investigated with histological/immunohistochemical markers for cortical laminar architecture, mammalian target of rapamycin pathway activation and inhibition, cellular autophagy, and synaptic vesicle-mediated trafficking as well as proteomics analysis...
October 20, 2016: Annals of Neurology
Jin Kyung Kim, Hye-Mi Lee, Ki-Sun Park, Dong-Min Shin, Tae Sung Kim, Yi Sak Kim, Hyun-Woo Suh, Soo Yeon Kim, In Soo Kim, Jin-Man Kim, Ji-Woong Son, Kyung Mok Sohn, Sung Soo Jung, Chaeuk Chung, Sang-Bae Han, Chul-Su Yang, Eun-Kyeong Jo
Autophagy is an important antimicrobial effector process that defends against Mycobacterium tuberculosis (Mtb), the human pathogen causing tuberculosis (TB). MicroRNAs (miRNAs), endogenous noncoding RNAs, are involved in various biological functions and act as post-transcriptional regulators to target mRNAs. The process by which miRNAs affect antibacterial autophagy and host defense mechanisms against Mtb infections in human monocytes and macrophages is largely uncharacterized. In this study, we show that Mtb significantly induces the expression of MIR144*/hsa-miR-144-5p, which targets the 3'-untranslated region of DRAM2 (DNA damage regulated autophagy modulator 2) in human monocytes and macrophages...
October 20, 2016: Autophagy
Zuriñe Antón, Ane Landajuela, Javier H Hervás, L Ruth Montes, Sonia Hernández-Tiedra, Guillermo Velasco, Felix M Goñi, Alicia Alonso
The phospholipid cardiolipin (CL) has been proposed to play a role in selective mitochondrial autophagy, or mitophagy. CL externalization to the outer mitochondrial membrane would act as a signal for the human Atg8 ortholog subfamily, MAP1LC3 (LC3). The latter would mediate both mitochondrial recognition and autophagosome formation, ultimately leading to removal of damaged mitochondria. We have applied quantitative biophysical techniques to the study of CL interaction with various Atg8 human orthologs, namely LC3B, GABARAPL2 and GABARAP...
October 20, 2016: Autophagy
Lu Cao, Mingui Fu, Santosh Kumar, Anil Kumar
Methamphetamine (METH), a commonly used controlled substance, is known to exacerbate neuropathological dysfunction in HIV-infected individuals. The neuropathological manifestation results from cell death or dysfunction in the central nervous system (CNS) wherein autophagy is expected to have an important role. Autophagy is generally considered protective during deprivation/stress. However, excessive autophagy can be destructive, leading to autophagic cell death. This study was designed to investigate if METH and HIV-1 gp120 interact to induce autophagy in SVGA astrocytes, and whether autophagy is epiphenomenal or it has a role in METH- and gp120-induced cytotoxicity...
October 20, 2016: Cell Death & Disease
Xiangbin Song, Zifa Li, Fei Liu, Zhenyong Wang, Lin Wang
Previous study has demonstrated that puerarin (PU) exerts nephroprotective effect against Pb-induced cytotoxicity in primary rat proximal tubular (rPT) cells. Autophagy can protect cells from various cytotoxic stimuli, but its role in the process of PU against Pb-induced nephrotoxicity is still unknown. This study aims to investigate whether PU can alleviate Pb-induced renal damage by recovering autophagy. Data showed that Pb inhibited the autophagic flux, as evidenced by the accumulation of LC3-II and p62 as well as the confocal microscopy analysis of GFP-LC3 puncta and punctate spots of monodansylcadaverine staining, whereas coadministration of PU could restore Pb-induced autophagy inhibition...
October 20, 2016: Journal of Biochemical and Molecular Toxicology
Liping Liu, Tiedong Sun, Feng Xin, Wei Cui, Jianquan Guo, Jian Hu
AIMS: To study whether autophagy participates in the neuroprotective effect of nerve growth factor (NGF) on neurons treated with alcohol. METHODS: The autophagy-related markers were used to explore the role of autophagy in PC12 cells exposed to alcohol or pre-incubated with NGF before initiating the treatment with alcohol (100 mM; 6 h). PC12 cells were pre-incubated with 3-methyladenine (3-MA) (10 mM; 1 h) or rapamycin (100 nM; 1 h) before co-incubated with alcohol (100 mM; 6 h) in order to investigate the relationship between apoptosis and autophagy...
October 19, 2016: Alcohol and Alcoholism: International Journal of the Medical Council on Alcoholism
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