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Autophagy

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https://www.readbyqxmd.com/read/28107461/inhibition-of-fatty-acid-synthase-reduces-blastocyst-hatching-through-regulation-of-the-akt-pathway-in-pigs
#1
Jing Guo, Nam-Hyung Kim, Xiang-Shun Cui
Fatty acid synthase (FASN) is an enzyme responsible for the de novo synthesis of long-chain fatty acids. During oncogenesis, FASN plays a role in growth and survival rather than acting within the energy storage pathways. Here, the function of FASN during early embryonic development was studied using its specific inhibitor, C75. We found that the presence of the inhibitor reduced blastocyst hatching. FASN inhibition decreased Cpt1 expression, leading to a reduction in mitochondria numbers and ATP content. This inhibition of FASN resulted in the down-regulation of the AKT pathway, thereby triggering apoptosis through the activation of the p53 pathway...
2017: PloS One
https://www.readbyqxmd.com/read/28106883/pten-deficiency-permits-the-formation-of-pancreatic-cancer-in-the-absence-of-autophagy
#2
Mathias T Rosenfeldt, Jim O'Prey, Lucia Flossbach, Colin Nixon, Jennifer P Morton, Owen J Sansom, Kevin M Ryan
No abstract text is available yet for this article.
January 20, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28106854/the-effect-of-polyphenols-on-protein-degradation-pathways-implications-for-neuroprotection
#3
REVIEW
Parvana Hajieva
Human neurodegenerative diseases are accompanied by accumulation of heavily oxidized and aggregated proteins. However, the exact molecular reason is not fully elucidated yet. Insufficient cellular protein quality control is thought to play an important role in accumulating covalently oxidized misfolded proteins. Pharmacologically active polyphenols and their derivatives exhibit potential for preventive and therapeutic purposes against protein aggregation during neurodegeneration. Although these compounds act on various biochemical pathways, their role in stabilizing the protein degradation machinery at different stages may be an attractive therapeutical strategy to halt the accumulation of misfolded proteins...
January 19, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28106737/a-novel-combination-rnai-toward-warburg-effect-by-replacement-with-mir-145-and-silencing-of-ptbp1-induces-apoptotic-cell-death-in-bladder-cancer-cells
#4
Tomoaki Takai, Yuki Yoshikawa, Teruo Inamoto, Koichiro Minami, Kohei Taniguchi, Nobuhiko Sugito, Yuki Kuranaga, Haruka Shinohara, Minami Kumazaki, Takuya Tsujino, Kiyoshi Takahara, Yuko Ito, Yukihiro Akao, Haruhito Azuma
Bladder cancer is one of the most difficult malignancies to control. We explored the use of a novel RNA-interference method for a driver oncogene regulating cancer specific energy metabolism by the combination treatment with a small interfering RNA (siRNA) and a microRNA. After transfection of T24 and 253JB-V cells with miR-145 and/or siR-PTBP1, we examined the effects of cell growth and gene expression by performing the trypan blue dye exclusion test, Western blot, Hoechst 33342 staining, reverse transcription polymerase chain reaction (RT-PCR), and electron microscopy...
January 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106723/inhibition-of-autophagic-degradation-process-contributes-to-claudin-2-expression-increase-and-epithelial-tight-junction-dysfunction-in-tnf-%C3%AE-treated-cell-monolayers
#5
Cong Zhang, Junkai Yan, Yongtao Xiao, Yujie Shen, Jiazheng Wang, Wensong Ge, Yingwei Chen
Tight junction dysfunction plays a vital role in some chronic inflammatory diseases. Pro-inflammatory cytokines, especially tumor necrosis factor alpha (TNF-α), act as important factors in intestinal epithelial tight junction dysfunction during inflammatory conditions. Autophagy has also been shown to be crucial in tight junction function and claudin-2 expression, but whether autophagy has an effect on the change of claudin-2 expression and tight junction function induced by TNF-α is still unknown. To answer this question, we examined the expression of claudin-2 protein, transepithelial electrical resistance (TER), and permeability of cell monolayers, autophagy flux change, and lysosomal pH after TNF-α with or without PP242 treatment...
January 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106298/inhibition-of-inositol-1-4-5-trisphosphate-receptor-induce-breast-cancer-cell-death-through-deregulated-autophagy-and-cellular-bioenergetics
#6
Aru Singh, Megha Chagtoo, Swasti Tiwari, Nelson George, Bandana Chakravarti, Sajid Khan, Sripada Lakshmi, Madan M Godbole
Inositol 1,4,5-trisphosphate receptors (IP3 Rs) regulate autophagy in normal cells and are associated with metastasis in cancer cells. In breast cancer, however, the regulation and role of IP3 Rs is not clear. To study this we used MCF-7 breast cancer cell line and mouse model of breast cancer. Inhibiting IP3 R sub types resulted in compromised bioenergetics both in terms of glucose and mitochondrial metabolism. The siRNA mediated silencing of IP3 R or its blocking by its inhibitors Xestospongin C and 2-Amino-ethoxy diphenyl borate increased cell death and LC3II expression in MCF-7 cells as well as attenuated cellular bioenergetics...
January 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28106136/long-term-exposure-to-835%C3%A2-mhz-rf-emf-induces-hyperactivity-autophagy-and-demyelination-in-the-cortical-neurons-of-mice
#7
Ju Hwan Kim, Da-Hyeon Yu, Yang Hoon Huh, Eun Ho Lee, Hyung-Gun Kim, Hak Rim Kim
Radiofrequency electromagnetic field (RF-EMF) is used globally in conjunction with mobile communications. There are public concerns of the perceived deleterious biological consequences of RF-EMF exposure. This study assessed neuronal effects of RF-EMF on the cerebral cortex of the mouse brain as a proxy for cranial exposure during mobile phone use. C57BL/6 mice were exposed to 835 MHz RF-EMF at a specific absorption rate (SAR) of 4.0 W/kg for 5 hours/day during 12 weeks. The aim was to examine activation of autophagy pathway in the cerebral cortex, a brain region that is located relatively externally...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28105557/the-anticancer-drug-sunitinib-promotes-autophagyand-protects-from-neurotoxicity-in-an-hiv-1-tat-model-of-neurodegeneration
#8
Jerel A Fields, Jeff Metcalf, Cassia Overk, Anthony Adame, Brian Spencer, Wolfgang Wrasidlo, Jazmin Florio, Edward Rockenstein, Johnny J He, Eliezer Masliah
Despite the success of antiretroviral therapies to control systemic HIV-1 infection, the prevalence of HIV-associated neurocognitive disorders (HANDs) has not decreased among aging patients with HIV. Autophagy pathway alterations, triggered by HIV-1 proteins including gp120, Tat, and Nef, might contribute to the neurodegenerative process in aging patients with HAND. Although no treatments are currently available to manage HAND, we have previously shown that sunitinib, an anticancer drug that blocks receptor tyrosine-kinase and cyclin kinase pathways, might be of interest...
January 19, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28105281/n-1-benzyl-3-5-dimethyl-1h-pyrazol-4-yl-benzamides-antiproliferative-activity-and-effects-on-mtorc1-and-autophagy
#9
Teng Ai, Rose Willett, Jessica Williams, Rui Ding, Daniel J Wilson, Jiashu Xie, Do-Hyung Kim, Rosa Puertollano, Liqiang Chen
Guided by antiproliferative activity in MIA PaCa-2 cells, we have performed preliminary structure-activity relationship studies on N-(1-benzyl-3,5-dimethyl-1H-pyrazol-4-yl)benzamides. Two selected compounds showed submicromolar antiproliferative activity and good metabolic stability. Both compounds reduced mTORC1 activity and increased autophagy at the basal level. In addition, they disrupted autophagic flux by interfering with mTORC1 reactivation and clearance of LC3-II under starvation/refeed conditions, as evidenced by accumulation of LC3-II and abnormal LC3 labeled punctae...
January 12, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28105213/wogonin-induces-beclin-1-pi3k-and-reactive-oxygen-species-mediated-autophagy-in-human-pancreatic-cancer-cells
#10
Shao-Jun Li, Shi-Jie Sun, Jie Gao, Fu-Bo Sun
Wogonin is considered to be an inhibitor of myeloid cell leukemia 1 and B-cell lymphoma 2, and a potential antitumor drug due to its ability to induce apoptosis in certain cancer cells; however, few previous studies have reported on wogonin-induced autophagy. The aim of the present study was to investigate the influence of wogonin on autophagy in human pancreatic cancer cells (HPCCs), elucidate its mechanism, and identify strategies to increase its effectiveness as an anti-cancer treatment. HPCCs were treated with wogonin and autophagy was detected in the cells...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28105210/mammalian-target-of-rapamycin-inhibitor-rad001-sensitizes-endometrial-cancer-cells-to-paclitaxel-induced-apoptosis-via-the-induction-of-autophagy
#11
Huan Wang, Dandan Li, Xiaomao Li, Xueling Ou, Suiling Liu, Yu Zhang, Jie Ding, Bo Xie
The aim of the present study was to investigate the effects of the mammalian target of rapamycin (mTOR) inhibitor, RAD001, on the growth of human endometrial cancer cells. The effects of RAD001 on human endometrial cancer Ishikawa and HEC-1A cell proliferation were determined by MTT assay. Green fluorescent protein microtubule-associated protein 1 light chain 3α (GFP-LC3) protein aggregates were observed under a confocal microscope, and Ishikawa and HEC-1A cell apoptosis was detected using flow cytometry. The expression levels of LC3-I, LC3-II and mTOR proteins were detected by western blot analysis...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28105169/role-of-wnt-%C3%AE-catenin-pathway-in-inducing-autophagy-and-apoptosis-in-multiple-myeloma-cells
#12
Nan Su, Pingping Wang, Yan Li
β-catenin is the downstream effector of the Wnt signaling pathway, which regulates cell proliferation and differentiation. Activation of the Wnt/β-catenin signaling pathway has been shown to positively correlate with prognosis in several types of malignancies. The present study aimed to determine the role of β-catenin in multiple myeloma (MM) cells using lentiviruses expressing small interfering RNA (siRNA). The expression of β-catenin in the MM cell line RPMI-8826 was evaluated following β-catenin knockdown by the siRNA...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28105121/expression-of-decorin-in-intestinal-tissues-of-mice-with-inflammatory-bowel-disease-and-its-correlation-with-autophagy
#13
Huazhou Zhao, Hongqing Xi, Bo Wei, Aizhen Cai, Ting Wang, Yi Wang, Xudong Zhao, Yanjing Song, Lin Chen
The aim of this study was to investigate the expression of decorin (DCN) in the intestinal tissues of mice with inflammatory bowel disease (IBD) and its correlation with autophagy. The IBD mouse model was created by intrarectal injection of trinitrobenzene sulfonic acid. The pathology of colon tissues of the mice was examined using hematoxylin and eosin staining. Expression of DCN and the proteins associated with autophagy was detected using immunohistochemistry. Normal human colon mucosal epithelial cells (NCM460 cells) were transfected with DCN expression plasmid and the expression of DCN and autophagy-associated proteins was detected by western blot analysis...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28104793/rab23-s-genetic-structure-function-and-related-diseases-a-review
#14
Li-Qiang Zheng, Su-Min Chi, Cheng-Xin Li
Rab23, has been proven to play a role in membrane trafficking and protein transport in eukaryotic cells. Rab23 is also a negative regulator of the Sonic hedgehog signaling pathway in an indirect way. The nonsense mutation and loss of protein of Rab23 has been associated with neural tube defect in mice and aberrant expression in various diseases in human such as neural system,breast, visceral and cutaneous tumor. In addition, Rab23 may play joint  roles in autophagosome formation during anti-infection process against  Group A streptococcus...
January 19, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28104670/mutants-for-drosophila-isocitrate-dehydrogenase-3b-are-defective-in-mitochondrial-function-and-larval-cell-death
#15
Dianne M Duncan, Paula Kiefel, Ian Duncan
The death of larval salivary gland cells during metamorphosis in Drosophila melanogaster has been a key system for studying steroid controlled programmed cell death. This death is induced by a pulse of the steroid hormone ecdysone that takes place at the end of the prepupal period. For many years, it has been thought that the ecdysone direct response gene Eip93F (E93) plays a critical role in initiating salivary gland cell death. This conclusion was based largely on the finding that the three "type" alleles of E93 cause a near-complete block in salivary gland cell death...
January 18, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28104575/modulation-of-proteostasis-by-transcription-factor-nrf2-and-impact-in-neurodegenerative-diseases
#16
REVIEW
Marta Pajares, Antonio Cuadrado, Ana I Rojo
Neurodegenerative diseases are linked to the accumulation of specific protein aggregates, suggesting an intimate connection between injured brain and loss of proteostasis. Proteostasis refers to all the processes by which cells control the abundance and folding of the proteome thanks to a wide network that integrates the regulation of signaling pathways, gene expression and protein degradation systems. This review attempts to summarize the most relevant findings about the transcriptional modulation of proteostasis exerted by the transcription factor NRF2 (nuclear factor (erythroid-derived 2)-like 2)...
January 10, 2017: Redox Biology
https://www.readbyqxmd.com/read/28104298/kr%C3%A3-pple-like-factor-10-regulates-radio-sensitivity-of-pancreatic-cancer-via-uv-radiation-resistance-associated-gene
#17
Vincent Hung-Shu Chang, Yi-Chih Tsai, Ya-Li Tsai, Shu-Ling Peng, Su-Liang Chen, Tsung Ming Chang, Winston Chun-Yuan Yu, Hui-Ju Ch'ang
BACKGROUND AND PURPOSE: Krüpple-like factor 10 (Klf10), an early response gene of TGFβ, was reported to be a prognostic biomarker for pancreatic cancer survival. The role of Klf10 in predicting tumor response to cancer treatment is unknown. MATERIALS AND METHODS: Genetically manipulated MiaPaCa and Panc-1 cells were established to evaluate clonogenic survival, autophagy, apoptosis and DNA repair after radiation. The interaction between Klf10 and UV radiation resistance-associated gene (UVRAG) was demonstrated by ChiP-PCR and luciferase reporter assay...
January 16, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28103798/selenium-suppresses-glutamate-induced-cell-death-and-prevents-mitochondrial-morphological-dynamic-alterations-in-hippocampal-ht22-neuronal-cells
#18
Yan-Mei Ma, Gordon Ibeanu, Li-Yao Wang, Jian-Zhong Zhang, Yue Chang, Jian-Da Dong, P Andy Li, Li Jing
BACKGROUND: Previous studies have indicated that selenium supplementation may be beneficial in neuroprotection against glutamate-induced cell damage, in which mitochondrial dysfunction is considered a major pathogenic feature. However, the exact mechanisms by which selenium protects against glutamate-provoked mitochondrial perturbation remain ambiguous. In this study glutamate exposed murine hippocampal neuronal HT22 cell was used as a model to investigate the underlying mechanisms of selenium-dependent protection against mitochondria damage...
January 19, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28103582/ampk-autophagy-inhibition-sensitizes-icaritin-induced-anti-colorectal-cancer-cell-activity
#19
Chunxian Zhou, Jun Gu, Gang Zhang, Da Dong, Qunying Yang, Min-Bin Chen, Dongfeng Xu
The current research studied the potential effect of autophagy on icaritin-induced anti-colorectal cancer (CRC) cell activity. Treatment of icaritin in both primary and established (HT-29) CRC cells induced feedback activation of autophagy, evidenced by p62 degradation, Beclin-1 and autophagy-related gene-5 (ATG-5) upregulation, as well as light chain 3B (LC3B)-GFP puncta formation. Pharmacological inhibiting of autophagy dramatically potentiated icaritin-induced CRC cell death and apoptosis. Meanwhile, shRNA-mediated knockdown of Beclin-1 or ATG-5 also sensitized icaritin-induced CRC cell death and apoptosis...
January 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28103122/ptk2-mediated-degradation-of-atg3-impedes-cancer-cells-susceptible-to-dna-damage-treatment
#20
Ke Ma, Wan Fu, Ming Tang, Chaohua Zhang, Tianyun Hou, Ran Li, Xiaopeng Lu, Yanan Wang, Jingyi Zhou, Xue Li, Luyao Zhang, Lina Wang, Ying Zhao, Wei-Guo Zhu
ATG3 (autophagy related 3) is an E2-like enzyme essential for autophagy; however, it is unknown whether it has an autophagy-independent function. Here, we report that ATG3 is a relatively stable protein in unstressed cells, but it is degraded in response to DNA-damaging agents such as etoposide or cisplatin. With mass spectrometry and a mutagenesis assay, phosphorylation of tyrosine 203 of ATG3 was identified to be a critical modification for its degradation, which was further confirmed by manipulating ATG3(Y203E) (phosphorylation mimic) or ATG3(Y203F) (phosphorylation-incompetent) in Atg3 knockout MEFs...
January 19, 2017: Autophagy
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