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Autophagy

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https://www.readbyqxmd.com/read/28633005/autophagy-impairment-mediated-by-s-nitrosation-of-atg4b-leads-to-neurotoxicity-in-response-to-hyperglycemia
#1
Yazi Li, Yuying Zhang, Lei Wang, Ping Wang, Yanhong Xue, Xiaopeng Li, Xinhua Qiao, Xu Zhang, Tao Xu, Guanghui Liu, Peng Li, Chang Chen
The majority of diabetic patients develop neuropathy and there is an increasing prevalence of neurodegeneration in the central nervous system (CNS). However, the mechanism behind is poorly understood. Here we first observed that macroautophagy/autophagy was suppressed in the hippocampus of diabetic GK rats with hyperglycemia, whereas it was unchanged in ob/ob mice without hyperglycemia. Autophagy could be directly inhibited by high glucose in mouse primary hippocampal neurons. Moreover, autophagy was protective in high-glucose-induced neurotoxicity...
June 20, 2017: Autophagy
https://www.readbyqxmd.com/read/28632995/microenvironment-and-tumors-a-nurturing-relationship
#2
Nadja Sandra Katheder, Tor Erik Rusten
No abstract text is available yet for this article.
June 20, 2017: Autophagy
https://www.readbyqxmd.com/read/28614042/bnip3l-nix-dependent-mitophagy-regulates-cell-differentiation-via-metabolic-reprogramming
#3
Lorena Esteban-Martínez, Patricia Boya
Macroautophagy/autophagy is the process by which cellular components are degraded and recycled within the lysosome. These components include mitochondria, the selective degradation of which is known as mitophagy. Mitochondria are dynamic organelles that constantly adapt their morphology, function, and number to accommodate the metabolic needs of the cell. Extensive metabolic reconfiguration occurs during cell differentiation, when mitochondrial activity increases in most cell types. However, our data demonstrate that during physiological retinal ganglion cell (RGC) development, mitophagy-dependent metabolic reprogramming towards glycolysis regulates numbers of RGCs, which are the first neurons to differentiate in the retina and whose axons form the optic nerve...
June 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28614034/sqstm1-p62-sequestosome-1-senses-cellular-ubiquitin-stress-through-e2-mediated-ubiquitination
#4
Jiao Yang, Hong Peng, Xiaoduo Xie, Ronggui Hu
The alterations in cellular ubiquitin (Ub) homeostasis, known as Ub stress, feature and affect cellular responses in multiple conditions, yet the underlying mechanisms are incompletely understood. We recently report that the macroautophagy/autophagy receptor SQSTM1/p62, functions as a novel Ub sensor to activate autophagy upon Ub(+) stress (upregulation of the Ub level). First, SQSTM1 was found to undergo extensive ubiquitination and activate autophagy under Ub(+) stress induced by prolonged Bortezomib (BTZ) treatment, Ub overexpression or by heat shock...
June 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28613987/methyl-%C3%AE-cyclodextrin-restores-impaired-autophagy-flux-in-niemann-pick-c1-deficient-cells-through-activation-of-ampk
#5
Sheng Dai, Andrés E Dulcey, Xin Hu, Christopher A Wassif, Forbes D Porter, Christopher P Austin, Daniel S Ory, Juan Marugan, Wei Zheng
The drug 2-hydroxypropyl-β-cyclodextrin (HPβCD) reduces lysosomal cholesterol accumulation in Niemann-Pick disease, type C (NPC) and has been advanced to human clinical trials. However, its mechanism of action for reducing cholesterol accumulation in NPC cells is uncertain and its molecular target is unknown. We found that methyl-β-cyclodextrin (MβCD), a potent analog of HPβCD, restored impaired macroautophagy/autophagy flux in Niemann-Pick disease, type C1 (NPC1) cells. This effect was mediated by a direct activation of AMP-activated protein kinase (AMPK), an upstream kinase in the autophagy pathway, through MβCD binding to its β-subunits...
June 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28613983/azithromycin-attenuates-myofibroblast-differentiation-and-lung-fibrosis-development-through-proteasomal-degradation-of-nox4
#6
Kazuya Tsubouchi, Jun Araya, Shunsuke Minagawa, Hiromichi Hara, Akihiro Ichikawa, Nayuta Saito, Tsukasa Kadota, Nahoko Sato, Masahiro Yoshida, Yusuke Kurita, Kenji Kobayashi, Saburo Ito, Yu Fujita, Hirofumi Utsumi, Haruhiko Yanagisawa, Mitsuo Hashimoto, Hiroshi Wakui, Yutaka Yoshii, Takeo Ishikawa, Takanori Numata, Yumi Kaneko, Hisatoshi Asano, Makoto Yamashita, Makoto Odaka, Toshiaki Morikawa, Katsutoshi Nakayama, Yoichi Nakanishi, Kazuyoshi Kuwano
Accumulation of profibrotic myofibroblasts is involved in the process of fibrosis development during idiopathic pulmonary fibrosis (IPF) pathogenesis. TGFB (transforming growth factor beta) is one of the major profibrotic cytokines for myofibroblast differentiation and NOX4 (NADPH oxidase 4) has an essential role in TGFB-mediated cell signaling. Azithromycin (AZM), a second-generation antibacterial macrolide, has a pleiotropic effect on cellular processes including proteostasis. Hence, we hypothesized that AZM may regulate NOX4 levels by modulating proteostasis machineries, resulting in inhibition of TGFB-associated lung fibrosis development...
June 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28613975/activation-of-drd5-dopamine-receptor-d5-inhibits-tumor-growth-by-autophagic-cell-death
#7
Zhi Gen Leng, Shao Jian Lin, Ze Rui Wu, Yu Hang Guo, Lin Cai, Han Bing Shang, Hao Tang, Ya Jun Xue, Mei Qing Lou, Wenxiu Zhao, Wei-Dong Le, Wei Guo Zhao, Xun Zhang, Zhe Bao Wu
Dopamine agonists such as bromocriptine and cabergoline have been successfully used in the treatment of pituitary prolactinomas and other neuroendocrine tumors. However, their therapeutic mechanisms are not fully understood. In this study we demonstrated that DRD5 (dopamine receptor D5) agonists were potent inhibitors of pituitary tumor growth. We further found that DRD5 activation increased production of reactive oxygen species (ROS), inhibited the MTOR pathway, induced macroautophagy/autophagy, and led to autophagic cell death (ACD) in vitro and in vivo...
June 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28613094/an-iron-hand-over-cancer-stem-cells
#8
Ahmed Hamaï, Tatiana Cañeque, Sebastian Müller, Trang Thi Mai, Antje Hienzsch, Christophe Ginestier, Emmanuelle Charafe-Jauffret, Patrice Codogno, Maryam Mehrpour, Raphaël Rodriguez
The paradigm of cancer stem cells (CSCs) defines the existence of cells exhibiting self-renewal and tumor-seeding capacity. These cells have been associated with tumor relapse and are typically resistant to conventional chemotherapeutic agents. Over the past decade, chemical biology studies have revealed a significant number of small molecules able to alter the proliferation of these cells in various settings. The natural product salinomycin has emerged as the most promising anti-CSC agent. However, an explicit mechanism of action has not yet been characterized, in particular due to the pleiotropic responses salinomycin is known for...
June 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28605287/prdx1-peroxiredoxin-1-deficiency-reduces-cholesterol-efflux-via-impaired-macrophage-lipophagic-flux
#9
Se-Jin Jeong, Sinai Kim, Jong-Gil Park, In-Hyuk Jung, Mi-Ni Lee, Sejin Jeon, Hyae Yon Kweon, Dae-Yeul Yu, Sang-Hak Lee, Yangsoo Jang, Sang Won Kang, Ki-Hwan Han, Yury I Miller, Young Mi Park, Cheolho Cheong, Jae-Hoon Choi, Goo Taeg Oh
Oxidative stress activates macroautophagy/autophagy and contributes to atherogenesis via lipophagic flux, a form of lipid removal by autophagy. However, it is not known exactly how endogenous anti-oxidant enzymes are involved in lipophagic flux. Here, we demonstrate that the anti-oxidant PRDX1 (peroxiredoxin 1) has a crucial role in the maintenance of lipophagic flux in macrophages. PRDX1 is more highly expressed than other anti-oxidant enzymes in monocytes and macrophages. We determined that Prdx1 deficiency induced excessive oxidative stress and impaired maintenance of autophagic flux in macrophages...
June 12, 2017: Autophagy
https://www.readbyqxmd.com/read/28598244/accumulation-of-undegraded-autophagosomes-by-expression-of-dominant-negative-stx17-syntaxin-17-mutants
#10
Masaaki Uematsu, Taki Nishimura, Yuriko Sakamaki, Hayashi Yamamoto, Noboru Mizushima
Macroautophagy/autophagy, which is one of the main degradation systems in the cell, is mediated by a specialized organelle, the autophagosome. Purification of autophagosomes prior to fusion with lysosomes is important for both mechanistic and physiological studies of the autophagosome. Here, we report a simple method to accumulate undigested autophagosomes. Overexpression of the autophagosomal Qa-SNARE STX17 (syntaxin 17) lacking the N-terminal domain (NTD) or N-terminally tagged GFP-STX17 causes accumulation of autophagosomes...
June 9, 2017: Autophagy
https://www.readbyqxmd.com/read/28598240/classical-autophagy-proteins-lc3b-and-atg4b-facilitate-melanosome-movement-on-cytoskeletal-tracks
#11
Amrita Ramkumar, Divya Murthy, Desingu Ayyappa Raja, Archana Singh, Anusha Krishnan, Sangeeta Khanna, Archana Vats, Lipi Thukral, Pushkar Sharma, Sridhar Sivasubbu, Rajni Rani, Vivek T Natarajan, Rajesh S Gokhale
Macroautophagy/autophagy is a dynamic and inducible catabolic process that responds to a variety of hormonal and environmental cues. Recent studies highlight the interplay of this central pathway in a variety of pathophysiological diseases. Although defective autophagy is implicated in melanocyte proliferation and pigmentary disorders, the mechanistic relationship between the 2 pathways have not been elucidated. In this study, we show that autophagic proteins LC3B and ATG4B mediate melanosome trafficking on cytoskeletal tracks...
June 9, 2017: Autophagy
https://www.readbyqxmd.com/read/28598236/destructive-cellular-paths-underlying-familial-and-sporadic-parkinson-disease-converge-on-mitophagy
#12
Xinnan Wang
The knowledge gap separating the molecular and cellular underpinnings of Parkinson disease (PD) and its pathology hinders treatment innovation. Adding to this difficulty is the lack of a reliable biomarker for PD. Our previous studies identify a link of 2 PD proteins, PINK1 and PRKN/Parkin to a mitochondrial motor/adaptor RHOT1/Miro-1, which mediates mitochondrial motility and mitophagy. Here we review our recent paper showing that a third PD protein, LRRK2, also targets RHOT1 and regulates mitophagy, and pathogenic LRRK2 disrupts this function...
June 9, 2017: Autophagy
https://www.readbyqxmd.com/read/28598235/lift-and-cut-anti-host-autophagy-mechanism-of-legionella-pneumophila
#13
Supansa Pantoom, Aimin Yang, Yao-Wen Wu
RavZ, an effector protein of pathogenic Legionella pneumophila, inhibits host macroautophagy/autophagy by deconjugation of lipidated LC3 proteins from phosphatidylethanolamine (PE) on the autophagosome membrane. The mechanism for how RavZ specifically recognizes and deconjugates the lipidated LC3s is not clear. To understand the structure-function relationship of LC3-deconjugation by RavZ, we prepared semisynthetic LC3 proteins modified with different fragments of PE or 1-hexadecanol (C16). We find that RavZ activity is strictly dependent on the conjugated PE structure and RavZ extracts LC3-PE from the membrane before deconjugation...
June 9, 2017: Autophagy
https://www.readbyqxmd.com/read/28598233/functional-impairment-in-rhot1-miro1-degradation-and-mitophagy-is-a-shared-feature-in-familial-and-sporadic-parkinson-disease
#14
Vikramjit Lahiri, Daniel J Klionsky
Mitophagy is a conserved and highly regulated process of selective degradation crucial in maintaining normal cellular physiology. Genetic defects and cellular aberrations affecting mitophagy have been associated with the development of Parkinson disease. In their recently published article (highlighted in a punctum in this issue of the journal) Hsieh et al. present a putative mitophagy marker which serves as a mechanistic link between sporadic and familial Parkinson disease.
June 9, 2017: Autophagy
https://www.readbyqxmd.com/read/28598232/exercise-reestablishes-autophagic-flux-and-mitochondrial-quality-control-in-heart-failure
#15
Juliane C Campos, Bruno B Queliconi, Luiz H M Bozi, Luiz R G Bechara, Paulo M M Dourado, Allen M Andres, Paulo R Jannig, Kátia M S Gomes, Vanessa O Zambelli, Cibele Rocha-Resende, Silvia Guatimosim, Patricia C Brum, Daria Mochly-Rosen, Roberta A Gottlieb, Alicia J Kowaltowski, Julio C B Ferreira
We previously reported that facilitating the clearance of damaged mitochondria through macroautophagy/autophagy protects against acute myocardial infarction. Here we characterized the impact of exercise, a safe strategy against cardiovascular disease, on cardiac autophagy and its contribution to mitochondrial quality control, bioenergetics and oxidative damage in a post-myocardial infarction-induced heart failure animal model. We found that failing hearts displayed reduced autophagic flux depicted by accumulation of autophagy-related markers and loss of responsiveness to chloroquine treatment at 4 and 12 weeks after myocardial infarction...
June 9, 2017: Autophagy
https://www.readbyqxmd.com/read/28598230/protective-mechanism-of-fsh-against-oxidative-damage-in-mouse-ovarian-granulosa-cells-by-repressing-autophagy
#16
Ming Shen, Yi Jiang, Zhiqiang Guan, Yan Cao, Liechuan Li, Honglin Liu, Shao-Chen Sun
Oxidative stress-induced granulosa cell (GCs) death represents a common reason for follicular atresia. Follicle-stimulating hormone (FSH) has been shown to prevent GCs from oxidative injury, although the underlying mechanism remains to be elucidated. Here we first report that the suppression of autophagic cell death via some novel signaling effectors is engaged in FSH-mediated GCs protection against oxidative damage. The decline in GCs viability caused by oxidant injury was remarkably reduced following FSH treatment, along with impaired macroautophagic/autophagic flux under conditions of oxidative stress both in vivo and in vitro...
June 9, 2017: Autophagy
https://www.readbyqxmd.com/read/28598229/autophagy-in-natural-and-therapy-driven-anticancer-immunosurveillance
#17
Federico Pietrocola, José Manuel Bravo-San Pedro, Lorenzo Galluzzi, Guido Kroemer
Autophagy is primordial for the maintenance of metabolic and genetic homeostasis in all eukaryotic organisms. Owing to its cell-intrinsic effects, autophagy robustly inhibits malignant transformation, yet can support the progression of established neoplasms as well as their resistance to conventional treatments. The notion that autophagy inhibition sensitizes neoplastic cells to chemotherapy and radiation therapy rivals with the capacity of autophagy to contribute to natural and therapy-driven anticancer immunosurveillance via a multitude of mechanisms...
June 9, 2017: Autophagy
https://www.readbyqxmd.com/read/28598226/mtor-controls-genesis-and-autophagy-of-gabaergic-interneurons-during-brain-development
#18
Minhan Ka, Amanda L Smith, Woo-Yang Kim
Interneuron progenitors in the ganglionic eminence of the ventral telencephalon generate most cortical interneurons during brain development. However, the regulatory mechanism of interneuron progenitors remains poorly understood. Here, we show that MTOR (mechanistic target of rapamycin [serine/threonine kinase]) regulates proliferation and macroautophagy/autophagy of interneuron progenitors in the developing ventral telencephalon. To investigate the role of MTOR in interneuron progenitors, we conditionally deleted the Mtor gene in mouse interneuron progenitors and their progeny by using Tg(mI56i-cre,EGFP)1Kc/Dlx5/6-Cre-IRES-EGFP and Nkx2-1-Cre drivers...
June 9, 2017: Autophagy
https://www.readbyqxmd.com/read/28594263/phototrophy-and-starvation-based-induction-of-autophagy-upon-removal-of-gcn5-catalyzed-acetylation-of-atg7-in-magnaporthe-oryzae
#19
Shulin Zhang, Meiling Liang, Naweed Naqvi, Chaoxiang Lin, Wanqiang Qian, Lian-Hui Zhang, Yi Zhen Deng
Magnaporthe oryzae, the ascomycete fungus that causes rice blast disease, initiates conidiation in response to light when grown on Prune-Agar medium containing both carbon and nitrogen sources. Macroautophagy/autophagy was shown to be essential for M. oryzae conidiation and induced specifically upon exposure to light but is undetectable in the dark. Therefore, it is inferred that autophagy is naturally induced by light, rather than by starvation during M. oryzae conidiation. However, the signaling pathway(s) involved in such phototropic induction of autophagy remains unknown...
June 8, 2017: Autophagy
https://www.readbyqxmd.com/read/28594260/thermoresponsive-nanocomposite-gel-for-local-drug-delivery-to-suppress-the-growth-of-glioma-by-inducing-autophagy
#20
Li Ding, Qi Wang, Ming Shen, Ying Sun, Xiangyu Zhang, Can Huang, Jianhua Chen, Rongxin Li, Yourong Duan
Although the treatments of malignant glioma include surgery, radiotherapy and chemotherapy by oral drug administration, the prognosis of patients with glioma remains very poor. We developed a polyethylene glycol-dipalmitoylphosphatidyle- thanoiamine (mPEG-DPPE) calcium phosphate nanoparticles (NPs) injectable thermoresponsive hydrogel (nanocomposite gel) that could provide a sustained and local delivery of paclitaxel (PTX) and temozolomide (TMZ). In addition, the proportion of PTX and TMZ for the optimal synergistic antiglioma effect on C6 cells was determined to be 1:100 (w/w) by the Chou and Talalay method...
June 8, 2017: Autophagy
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