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https://www.readbyqxmd.com/read/28821708/a-reversible-phospho-switch-mediated-by-ulk1-regulates-the-activity-of-autophagy-protease-atg4b
#1
N Pengo, A Agrotis, K Prak, J Jones, R Ketteler
Upon induction of autophagy, the ubiquitin-like protein LC3 is conjugated to phosphatidylethanolamine (PE) on the inner and outer membrane of autophagosomes to allow cargo selection and autophagosome formation. LC3 undergoes two processing steps, the proteolytic cleavage of pro-LC3 and the de-lipidation of LC3-PE from autophagosomes, both executed by the same cysteine protease ATG4. How ATG4 activity is regulated to co-ordinate these events is currently unknown. Here we find that ULK1, a protein kinase activated at the autophagosome formation site, phosphorylates human ATG4B on serine 316...
August 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28819136/the-possible-molecular-mechanisms-of-bisphenol-a-action-on-porcine-early-embryonic-development
#2
Jing Guo, Ming-Hui Zhao, Kyung-Tae Shin, Ying-Jie Niu, Yong-Dae Ahn, Nam-Hyung Kim, Xiang-Shun Cui
Bisphenol A (BPA) is an environmental contaminant widely used in the plastic industry. BPA has been demonstrated to be an endocrine disruptor and has an adverse effect on the embryonic development of mammals. However, the mechanism of action of BPA is limited. In this study, we investigated the role and mechanism of BPA in porcine embryonic development. First, the parthenotes were treated with different concentrations of BPA. We found that blastocyst formation was impaired and the parthenotes were arrested at the 4-cell stage after treatment with 100 μm BPA...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819100/blockage-of-the-lysosome-dependent-autophagic-pathway-contributes-to-complement-membrane-attack-complex-induced-podocyte-injury-in-idiopathic-membranous-nephropathy
#3
Wei Jing Liu, Zhi-Hang Li, Xiao-Cui Chen, Xiao-Lu Zhao, Zhen Zhong, Chen Yang, Hong-Luan Wu, Ning An, Wei-Yan Li, Hua-Feng Liu
Dysregulation of autophagy-mediated podocyte homeostasis is proposed to play a role in idiopathic membranous nephropathy (IMN). In the present study, autophagic activity and lysosomal alterations were investigated in podocytes of IMN patients and in cultured podocytes exposed to sublytic terminal complement complex, C5b-9. C5b-9 upregulated the number of LC3 positive puncta and the expression of p62 in patient podocytes and in C5b-9 injuried podocyte model. The lysosomal turnover of LC3-II was not influenced, although the BECN1 expression level was upregulated after exposure of podocytes to C5b-9...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28817179/autophagy-induction-plays-a-protective-role-against-hypoxic-stress-in-human-dental-pulp-cells
#4
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/28816044/action-of-gold-nanospikes-based-nanoradiosensitizers-cellular-internalization-radiotherapy-and-autophagy
#5
Ningning Ma, Peidang Liu, Nongyue He, Ning Gu, Fu-Gen Wu, Zhan Chen
A major challenge to achieve effective X-ray radiation therapy is to use a relatively low and safe radiation dose. Various radiosensitizers, which can significantly enhance the radiotherapeutic performance, have been developed. Gold-based nanomaterials, as a new type of nanoparticle-based radiosensitizers, have been extensively used in researches involving cancer radiotherapy. However, the cancer therapeutic effect using the gold nanoparticle-based radiotherapy is usually not significant because of the low cellular uptake efficiency and the autophagy-inducing ability of these gold nanomaterials...
August 17, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28815517/autophagy-in-adipocyte-differentiation
#6
Zhipeng Tao, Longhua Liu, Louise D Zheng, Zhiyong Cheng
Adipose tissue regulates metabolic homeostasis by acting as an endocrine organ and energy reservoir. Adipose tissue development and functional maintenance are dependent on adipocyte differentiation, in which autophagy plays an important role. It has been shown that autophagy deficiency dampens adipocyte differentiation, compromises adipose tissue development, dysregulates adipocytokine secretion, and even causes sudden death in young animals. Therefore, accurate assessment of autophagy in adipocyte is critical for the study of adipose biology or pathology of metabolic diseases...
August 17, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28815060/defective-expression-of-atg4d-abrogates-autophagy-and-promotes-growth-in-human-uterine-fibroids
#7
Abdeljabar El Andaloussi, Samar Habib, Gizem Soylemes, Archana Laknaur, Heba Elhusseini, Ayman Al-Hendy, Nahed Ismail
Uterine fibroids (UF) are the most common pelvic tumors in women of reproductive-age and they usually cause heavy menstrual bleeding, pain and infertility. Autophagy is a collection of processes that enables the cells to digest and recycle their cytoplasmic contents, such as toxic protein aggregates, defunct or disused organelles and invading microorganisms. Dysregulation in autophagy process were described in neoplasms; however, the contribution of autophagy to the pathogenesis of UF remains unknown. In this study, we demonstrate that autophagy is deregulated in human UF as evidenced by significant accumulation of autophagosome in human UF cells compared to normal myometrium cells...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28813698/caspase-independent-pathway-is-related-to-nilotinib-cytotoxicity-in-cultured-cardiomyocytes
#8
Qinghui Yang, Chunhui Zhang, Hong Wei, Zenghui Meng, Guangnan Li, Yuanyuan Xu, Yanjun Chen
BACKGROUND/AIMS: Cardiotoxicity is a predominant side-effect of nilotinib during chronic myeloid leukemia treatment. The underlying molecular mechanism remains unclear. The role of autophagy and mitochondrial signaling was investigated in nilotinib-treated cardiac H9C2 cells. METHODS: Cytotoxicity was assessed using Cell Death Detection kit. Immunoblot and immunofluorescence staining was performed, and cathepsin B and caspase3 activity was assessed in nilotinib-treated H9C2 cells with or without distinct pathway inhibitor or specific siRNA...
August 15, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28813181/pathway-choice-between-proteasomal-and-autophagic-degradation
#9
Kefeng Lu, Fabian den Brave, Stefan Jentsch
Efficient degradation of abnormal or aggregated proteins is crucial to protect the cell against proteotoxic stress. Selective targeting and disposal of such proteins usually occurs in a ubiquitin-dependent manner by proteasomes and macroautophagy/autophagy. Whereas proteasomes are efficient in degrading abnormal soluble proteins, protein aggregates are typically targeted for degradation by autophagic vesicles. Both processes require ubiquitin-binding receptors, which are targeted to proteasomes via ubiquitin-like domains or to phagophores (the precursors to autophagosomes) via Atg8/LC3 binding motifs, respectively...
August 16, 2017: Autophagy
https://www.readbyqxmd.com/read/28812433/regulation-of-sqstm1-p62-via-uba-domain-ubiquitination-and-its-role-in-disease
#10
YouJin Lee, Conrad C Weihl
Macroautophagy/autophagy can be a selective degradative process via the utilization of various autophagic receptor proteins. Autophagic receptors selectively recognize ubiquitinated cargoes and deliver them to phagophores, the precursors to autophagosomes, for their degradation. For example, SQSTM1/p62 directly binds to ubiquitinated protein aggregates via its UBA domain and sequesters them into inclusion bodies via its PB1 domain. SQSTM1also interacts with phagophores via its LC3-interacting (LIR) motif. However, a regulatory mechanism for autophagic receptors is not yet understood...
August 16, 2017: Autophagy
https://www.readbyqxmd.com/read/28811357/autophagy-attenuates-endothelial-to-mesenchymal-transition-by-promoting-snail-degradation-in-human-cardiac-microvascular-endothelial-cells
#11
Jin Zou, Yanhua Liu, Bingong Li, Zeqi Zheng, Xuan Ke, Yanqin Hao, Xuelian Li, Xingxing Li, Fuyou Liu, Zhiyong Zhang
Endothelial-to-mesenchymal transition (EndMT) mainly exists in cardiovascular development and disease progression, and is well known to contribute to cardiac fibrosis. Recent studies indicated that autophagy also participates in the regulation of cardiac fibrosis. However, the precise role of autophagy in cardiac fibrosis and the underlying molecular mechanism remain unclear. This study aimed to explore the role of autophagy in EndMT, reveal the underlying molecular mechanism and seek new therapy for cardiac fibrosis...
August 15, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28811097/type-i-collagen-promotes-primary-cilia-growth-through-down-regulating-hdac6-mediated-autophagy-in-confluent-mouse-embryo-fibroblast-3t3-l1-cells
#12
Qian Xu, Weiwei Liu, Xiaoling Liu, Wuxiyar Otkur, Toshihiko Hayashi, Masayuki Yamato, Hitomi Fujisaki, Shunji Hattori, Shin-Ichi Tashiro, Takashi Ikejima
Primary cilia are microtubule-based organelles that extend from nearly all vertebrate cells. Abnormal ciliogenesis and cilia length are suggested to be associated with hypertension and obesity as well as diseases such as Meckel-Gruber syndrome. Extracellular matrix (ECM), comprising cellular microenvironment, influences cell shape and proliferation. However, influence of ECM on cilia biogenesis has not been well studied. In this study we examined the effects of type I collagen (col I), the major component of ECM, on primary cilia growth...
August 12, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28810608/mechanism-of-microrna-21-regulating-il-6-inflammatory-response-and-cell-autophagy-in-intervertebral-disc-degeneration
#13
Hao Lin, Wenzhi Zhang, Tao Zhou, Wansu Li, Ziao Chen, Chaochao Ji, Chao Zhang, Fang He
This study investigated the mechanism of microRNA-21 in regulating IL-6 inflammatory response and cell autophagy in intervertebral disc degeneration. A total of 10 patients with lumbar disc herniation accompanied by nerve root pain (observation group) and 10 patients with lumbar burst fractures (control group) were selected. The nucleus pulposus tissues of the lesion were obtained during operation for cell culture. Real-time quantitative polymerase chain reaction (PCR) was used to detect the expression of microRNA-21...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810529/silymarin-induces-a-multi-targeted-cell-death-process-in-the-human-colon-cancer-cell-line-ht-29
#14
L Khorsandi, G Saki, N Bavarsad, M Mombeini
This study investigated the Silymarin (SM) effects on growth of HT-29 human colon cancer cell line and its cellular death mechanism. HT-29 cells were treated by 25μM/ml of SM for 48h. HT-29 cells were also pretreated with 10mmol zVAD (apoptosis inhibitor), 10mmol 3-MA (autophagy inhibitor) and 3mmol Nec (necroptosis inhibitor) for evaluation cell death induced by apoptosis, outophagy and necroptosis. MTT and clonogenicity assays revealed that the SM without inhibitors induced a significant decrease in cell viability and proliferation of HT-29 cells (p<0...
August 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28808420/inhibition-of-mtor-signaling-confers-protection-against-cerebral-ischemic-injury-in-acute-hyperglycemic-rats
#15
Changchun Hei, Ping Liu, Xiao Yang, Jianguo Niu, P Andy Li
Hyperglycemia is known to exacerbate neuronal death resulted from cerebral ischemia. The mechanisms are not fully understood. The mammalian target of rapamycin (mTOR) pathway regulates cell growth, division and apoptosis. Recent studies suggest that activation of mTOR may mediate ischemic brain damage. The objective of the present experiment is to explore whether mTOR mediates ischemic brain damage in acute hyperglycemic animals. Rats were subjected to 10 min of forebrain ischemia under euglycemic, hyperglycemic and rapamycin-treated hyperglycemic conditions...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28808340/kr%C3%A3-ppel-like-factor-6-is-a-transcriptional-activator-of-autophagy-in-acute-liver-injury
#16
Svenja Sydor, Paul Manka, Jan Best, Sami Jafoui, Jan-Peter Sowa, Miguel Eugenio Zoubek, Virginia Hernandez-Gea, Francisco Javier Cubero, Julia Kälsch, Diana Vetter, Maria Isabel Fiel, Yujin Hoshida, C Billie Bian, Leonard J Nelson, Han Moshage, Klaas Nico Faber, Andreas Paul, Hideo A Baba, Guido Gerken, Scott L Friedman, Ali Canbay, Lars P Bechmann
Krüppel-like factor 6 (KLF6) is a transcription factor and tumor suppressor. We previously identified KLF6 as mediator of hepatocyte glucose and lipid homeostasis. The loss or reduction of KLF6 is linked to the progression of hepatocellular carcinoma, but its contribution to liver regeneration and repair in acute liver injury are lacking so far. Here we explore the role of KLF6 in acute liver injury models in mice, and in patients with acute liver failure (ALF). KLF6 was induced in hepatocytes in ALF, and in both acetaminophen (APAP)- and carbon tetrachloride (CCl4)-treated mice...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808311/antitumor-properties-of-coenzyme-q0-against-human-ovarian-carcinoma-cells-via-induction-of-ros-mediated-apoptosis-and-cytoprotective-autophagy
#17
You-Cheng Hseu, Tai-Jung Tsai, Mallikarjuna Korivi, Jer-Yuh Liu, Hui-Jye Chen, Chung-Ming Lin, Yi-Chun Shen, Hsin-Ling Yang
Coenzyme Q0 (CoQ0, 2,3-dimethoxy-5-methyl-1,4-benzoquinone) has been reported to exert anticancer properties against human breast/lung cancer cells. This study investigated the in vitro and in vivo anticancer properties of CoQ0 on human ovarian carcinoma (SKOV-3) cells and xenografted nude mice, and revealed the underlying molecular mechanism. CoQ0 induced G2/M arrest through downregulation of cyclin B1/A and CDK1/K2 expressions. CoQ0-induced autophagy as a survival mechanism was evidenced by increased accumulation of LC3-II, GFP-LC3 puncta, AVOs formation and Beclin-1/Bcl-2 dysregulation...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28807642/alterations-of-apoptosis-and-autophagy-in-developing-brain-of-rats-with-epilepsy-changes-in-lc3-p62-beclin-1-and-bcl-2-levels
#18
Qinrui Li, Ying Han, Junbao Du, Hongfang Jin, Jing Zhang, Manman Niu, Jiong Qin
Current studies have indicated that apoptotic and autophagic signaling pathways are triggered by epileptic seizures, but the precise roles of these processes in epilepsy-induced neuronal loss remain unclear. Identifying a concrete molecular mechanism may help researchers develop relevant epilepsy therapies that are more effective than existing treatments. Autophagy is a type of conserved degradation that contributes to cellular homeostasis. The involved signaling pathways allow us to observe alterations in autophagy and apoptosis during epileptic seizures over time...
August 11, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28806134/ilir-viral-a-web-resource-for-lir-motif-containing-proteins-in-viruses
#19
Anne-Claire Jacomin, Siva Samavedam, Hannah Charles, Ioannis P Nezis
Macroautophagy/autophagy has been shown to mediate the selective lysosomal degradation of pathogenic bacteria and viruses (xenophagy), and to contribute to the activation of innate and adaptative immune responses. Autophagy can serve as an antiviral defense mechanism but also as a pro-viral process during infection. Atg8-family proteins play a central role in the autophagy process due to their ability to interact with components of the autophagy machinery as well as selective autophagy receptors and adaptor proteins...
August 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28806108/the-composition-of-a-protein-aggregate-modulates-the-specificity-and-efficiency-of-its-autophagic-degradation
#20
Gangming Zhang, Long Lin, Di Qi, Hong Zhang
The mechanism underlying autophagic degradation of a protein aggregate remains largely unknown. A family of receptor proteins that simultaneously bind to the cargo and the Atg8 family of autophagy proteins (such as the MAP1LC3/LC3 subfamily) has been shown to confer cargo selectivity. The selectivity and efficiency of protein aggregate removal is also modulated by scaffold proteins that interact with receptor proteins and ATG proteins. During C. elegans embryogenesis, autophagic clearance of the cargoes PGL-1 and PGL-3 requires the receptor protein SEPA-1 and the scaffold protein EPG-2...
August 14, 2017: Autophagy
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