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Aviram Kogot-Levin, Ann Saada, Gil Leibowitz, Devorah Soiferman, Liza Douiev, Itamar Raz, Sarah Weksler-Zangen
Cytochrome-c-oxidase (COX) deficiency is a frequent cause of mitochondrial disease and is associated with a wide spectrum of clinical phenotypes. We studied mitochondrial function and biogenesis in fibroblasts derived from the Cohen (CDs) rat, an animal model of COX deficiency. COX activity in CDs-fibroblasts was 50% reduced compared to control rat fibroblasts (P<0.01). ROS-production in CDs fibroblasts increased, along with marked mitochondrial fragmentation and decreased mitochondrial membrane-potential, indicating mitochondrial dysfunction...
2016: PloS One
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
G Kaur, M Pawlik, S E Gandy, M E Ehrlich, J F Smiley, E Levy
Recent data suggest that intraneuronal accumulation of metabolites of the amyloid-β-precursor protein (APP) is neurotoxic. We observed that transgenic mice overexpressing in neurons a human APP gene harboring the APP(E693Q) (Dutch) mutation have intraneuronal lysosomal accumulation of APP carboxylterminal fragments (APP-CTFs) and oligomeric amyloid β (oAβ) but no histological evidence of amyloid deposition. Morphometric quantification using the lysosomal marker protein 2 (LAMP-2) immunolabeling showed higher neuronal lysosomal counts in brain of 12-months-old APP(E693Q) as compared with age-matched non-transgenic littermates, and western blots showed increased lysosomal proteins including LAMP-2, cathepsin D and LC3...
October 25, 2016: Molecular Psychiatry
Amiya Kumar Ghosh, Theresa Mau, Martin O'Brien, Sanjay Garg, Raymond Yung
Adipose tissue dysfunction in aging is associated with inflammation, metabolic syndrome and other diseases. We propose that impaired protein homeostasis due to compromised lysosomal degradation (micro-autophagy) might promote aberrant ER stress response and inflammation in aging adipose tissue. Using C57BL/6 mouse model, we demonstrate that adipose tissue-derived stromal vascular fraction (SVF) cells from old (18-20 months) mice have reduced expression of autophagy markers as compared to the younger (4-6 months) cohort...
October 24, 2016: Aging
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
Lou-Yan Ma, Ya-Li Lv, Kang Huo, Jie Liu, Su-Hang Shang, Yu-Lang Fei, Yan-Bo Li, Bei-Yu Zhao, Meng Wei, Yong-Ning Deng, Qiu-Min Qu
β-Amyloid (Aβ) deposition has a central role in the pathogenesis of Alzheimer disease (AD). Previous studies have indicated that as a risk factor for AD, diabetes mellitus (DM) could induce Aβ deposition in the brain, but the mechanism is not fully elucidated. Autophagy-lysosome is a cellular pathway involved in protein and organelle degradation. In the present study, we used streptozotocin (STZ)-induced diabetic rats to investigate whether autophagy-lysosome is related to Aβ1-42 clearance in DM. We found that DM rats had a longer escape latency and less frequent entry into the target zone than that of the control group (p<0...
October 20, 2016: Behavioural Brain Research
Qinghua Chen, Lulu Zhang, Siyao Chen, Yaqian Huang, Kun Li, Xiaoqi Yu, Huijuan Wu, Xiaoyu Tian, Chunyu Zhang, Chaoshu Tang, Junbao Du, Hongfang Jin
BACKGROUND: The study was designed to investigate if endogenous sulfur dioxide (SO2) was involved in cardiomyocyte autophagy and myocardial hypertrophy stimulated by angiotensin II (Ang II). METHODS: Thirty-two C57 mice were randomly divided into control, SO2, Ang II and Ang II+SO2 groups. Human myocardial cell line H9c2 was divided into four groups including control, SO2, Ang II and Ang II+SO2 groups. Blood pressure and myocardial hypertrophy of the mice were measured two weeks after Ang II administration...
September 30, 2016: International Journal of Cardiology
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
Kwang-Youn Kim, Hyun-Jun Jang, Yong Ryul Yang, Kwang-Il Park, JeongKon Seo, Il-Woo Shin, Tae-Il Jeon, Soon-Cheol Ahn, Pann-Ghill Suh, Timothy F Osborne, Young-Kyo Seo
Dysregulated autophagy is associated with steatosis and non-alcoholic fatty liver disease (NAFLD), however the mechanisms connecting them remain poorly understand. Here, we show that co-administration of lovastatin and ezetimibe (L/E) significantly reverses hepatic triglyceride accumulation concomitant with an increase in SREBP-2 driven autophagy in mice fed a high-fat diet (HFD). We further show that the statin mediated increase in SREBP-2 directly activates expression of patatin-like phospholipase domain-containing enzyme 8 (PNPLA8) gene, and PNPLA8 associates with autophagosomes and is associated with a decrease in cellular triglyceride...
October 21, 2016: Scientific Reports
Alfredo Lagunas-Martínez, Enrique García-Villa, Magaly Arellano-Gaytán, Carla O Contreras-Ochoa, Jisela Dimas-González, María E López-Arellano, Vicente Madrid-Marina, Patricio Gariglio
The E6 oncoprotein can interfere with the ability of infected cells to undergo programmed cell death through the proteolytic degradation of proapoptotic proteins such as p53, employing the proteasome pathway. Therefore, inactivation of the proteasome through MG132 should restore the activity of several proapoptotic proteins. We investigated whether in HPV16 E6-expressing keratinocytes (KE6 cells), the restoration of p53 levels mediated by MG132 and/or activation of the CD95 pathway through apoptosis antigen-1 (APO-1) antibody are responsible for the induction of apoptosis...
October 20, 2016: Apoptosis: An International Journal on Programmed Cell Death
Xin-Shuang Yu, Juan Du, Yu-Jun Fan, Feng-Jun Liu, Li-Li Cao, Ning Liang, De-Guo Xu, Jian-Dong Zhang
OBJECTIVE: This study aims to investigate the effects of endoplasmic reticulum stress (ERS) on autophagy, apoptosis and chemoresistance of human small cell lung cancer (SCLC) cells via the PI3K/AKT/mTOR signaling pathway. RESULTS: The expressions of ERS-related proteins (PEAK, eIF2α and CHOP) up-regulated, autophagy-related proteins (LC3, LC3-II and Beclin1) and apoptosis-related proteins (Bax and procaspase-3) down-regulated in NCI-H446 and H69 cells after tunicamycin treatment for 24 h...
October 18, 2016: Oncotarget
Soojong Park, Ahmad Fudhaili, Sang-Seok Oh, Ki Won Lee, Hamadi Madhi, Dong-Hee Kim, Jiyun Yoo, Hyung Won Ryu, Ki-Hun Park, Kwang Dong Kim
BACKGROUND: Broussonetia papyrifera (B. papyrifera), also known as paper mulberry, has been used as a traditional medicine for the treatment of several diseases, including ophthalmic disorders and impotency. However, the biological activity of kazinol A (1) among flavonols isolated from B. papyrifera has not been identified. PURPOSE: We identified a candidate metabolite for anti-human bladder cancer treatment from B. papyrifera and investigated the possible molecular mechanisms underlying its cytotoxic effects in T24 and cisplatin-resistant T24R2 human bladder cancer cells...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
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
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
Adam P Rofe, Luther J Davis, Jean L Whittingham, Elizabeth C Latimer-Bowman, Anthony J Wilkinson, Paul R Pryor
Rhodococcus equi (R. equi) is an important pulmonary pathogen in foals that often leads to the death of the horse. The bacterium harbors a virulence plasmid that encodes numerous virulence-associated proteins (Vaps) including VapA that is essential for intracellular survival inside macrophages. However, little is known about the precise function of VapA. Here, we demonstrate that VapA causes perturbation to late endocytic organelles with swollen endolysosome organelles having reduced Cathepsin B activity and an accumulation of LBPA, LC3 and Rab7...
October 19, 2016: MicrobiologyOpen
Dan Yi, Yongqing Hou, Huimin Mei, Lei Wang, Chien-An Andy Hu, Guoyao Wu
β-Conglycinin (β-CG) is well known for inducing intestinal allergies and dysfunction in neonates and young pigs. However, the underlying mechanisms are largely unknown. In this study, to clarify the role of autophagy in β-CG-induced cytotoxicity, we investigated the effects of β-CG on cell viability and autophagy activity in porcine enterocytes (IPEC-1 cells). The results indicated that the cell viability was decreased with the increasing levels of β-CG. β-CG treatment enhanced the eGFP-LC3 puncta per cells and LC3-II/LC3-I, and the latter was further increased in IPEC-1 cells cultured with bafilomycin A1...
October 19, 2016: Amino Acids
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
X H Sun, M S Yin, Y L Mu
Objective: To investigate the alterations of mTOR signaling pathway and autophagy in the development of type 2 diabetes and early diabetic cardiomyopathy and to study their roles in pathogenesis of diabetic myocardium. Methods: A type 2 diabetes rat model was established by injection of streptozocin after five-week of high fat diet. The rats were randomly divided into control group, experiment group of 2 weeks and experiment group of 4 weeks. Alterations of mTOR, p-mTOR, S6K1, Beclin-1 and LC3-Ⅱ expression in myocardium were determined by Western blot and immunohistochemistry...
October 8, 2016: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
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