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https://www.readbyqxmd.com/read/28214874/heat-acclimation-regulates-the-autophagy-lysosome-function-to-protect-against-heat-stroke-induced-brain-injury-in-mice
#1
Junfeng Yi, Genlin He, Ju Yang, Zhen Luo, Xuesen Yang, Xue Luo
BACKGROUND/AIMS: The mechanisms underlying the protective role of heat acclimation (HA) in heat stroke (HS)-induced brain injury are still unclear. The autophagy-lysosome pathway is known to pay an important role in protecting stressed or diseased cells from death. Nevertheless, whether autophagy and lysosomes are involved in HA-mediated neuroprotection following HS exposure remains unclear. METHODS: The protective effects of HA were assessed by rectal temperature, hematoxylin-eosin staining, transmission electron microscopic analysis, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining, and Fluoro Jade B staining, after mice were subjected to HS...
January 18, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28214847/contribution-of-p62-to-phenotype-transition-of-coronary-arterial-myocytes-with-defective-autophagy
#2
Junxiang Bao, Guangbi Li, Xinxu Yuan, Pin-Lan Li, Erich Gulbins
BACKGROUND: Autophagy disorder contributes to dedifferentiation of arterial smooth muscle cells, but the mechanisms are poorly understood. Here, we sought to investigate the role of scaffolding adaptor p62/SQSTM1 (p62) in phenotype switching of mouse coronary arterial myocytes (CAMs) induced by CD38 gene deficiency or lysosomal dysfunction which blocks autophagic flux in the cells. METHODS: Protein expression was measured by western blot analysis and immunofluorescent staining...
February 3, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28212834/death-associated-protein-1-dap-1-positively-regulates-virus-replication-and-apoptosis-of-hemocytes-in-shrimp-marsupenaeus-japonicus
#3
Wen-Li Xia, Li-Hua Kang, Chang-Bin Liu, Cui-Jie Kang
Death-associated protein 1 (DAP1) is a small proline-rich cytoplasmic protein that functions both in the apoptosis and autophage process of mammalian and in the clinical cancer of human. However, little knowledge is known about the homologue gene of DAP1 and its roles in the physiological process of invertebrates. In this paper, we report a novel function of DAP1 in the antivirus immunity of shrimp. A homologue gene of DAP1 was cloned from Marsupenaeus japonicus and named as Mjdap-1. The full-length of Mjdap-1 was 1761 bp with a 309 bp open reading frame that encoded 102 amino acids...
February 14, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28212727/mitophagy-link-to-cancer-development-and-therapy
#4
REVIEW
Andrey V Kulikov, Ekaterina A Luchkina, Vladimir Gogvadze, Boris Zhivotovsky
Mitophagy, the selective degradation of mitochondria via the autophagic pathway, is a vital mechanism of mitochondrial quality control in cells. Mitophagy is responsible for the removal of malfunctioning or damaged mitochondria, which is essential for normal cellular physiology and tissue development. Pathways involved in the regulation of mitophagy, tumorigenesis, and cell death are overlapping in many cases and may be triggered by common upstream signals, which converge at the mitochondria. The failure to properly modulate mitochondrial turnover in response to oncogenic stresses can either stimulate or suppress tumorigenesis...
January 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28212571/activation-of-jnk-and-ire1-is-critically-involved-in-tanshinone-i-induced-p62-dependent-autophagy-in-malignant-pleural-mesothelioma-cells-implication-of-p62-uba-domain
#5
Jihyun Lee, Eun Jung Sohn, Sangwook Yoon, Gunho Won, Chang Geun Kim, Ji Hoon Jung, Sung-Hoon Kim
The aim of present study is to elucidate autophagic mechanism of tanshinone I (Tan I) in H28 and H2452 mesothelioma cells. Herein, Tan I exerted cytotoxicity with autophagic features of autophagy protein 5 (ATG5)/ microtubule-associated protein 1A/1B-light chain 3II (LC3 II) activation, p62/sequestosome 1 (SQSTM1) accumulation and increased number of LC3II punctae, acridine orange-stained cells and autophagic vacuoles. However, 3-methyladenine (3MA) and NH4Cl increased cytotoxicity in Tan I treated H28 cells...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212561/the-tlr7-agonist-imiquimod-induces-anti-cancer-effects-via-autophagic-cell-death-and-enhances-anti-tumoral-and-systemic-immunity-during-radiotherapy-for-melanoma
#6
Jeong Hyun Cho, Hyo-Ji Lee, Hyun-Jeong Ko, Byung-Il Yoon, Jongseon Choe, Keun-Cheol Kim, Tae-Wook Hahn, Jeong A Han, Sun Shim Choi, Young Mee Jung, Kee-Ho Lee, Yun-Sil Lee, Yu-Jin Jung
Toll-like receptor (TLR) ligands are strongly considered immune-adjuvants for cancer immunotherapy and have been shown to exert direct anti-cancer effects. This study was performed to evaluate the synergistic anti-cancer and anti-metastatic effects of the TLR7 agonist imiquimod (IMQ) during radiotherapy for melanoma. The pretreatment of B16F10 or B16F1 cells with IMQ combined with γ-ionizing radiation (IR) led to enhanced cell death via autophagy, as demonstrated by increased expression levels of autophagy-related genes, and an increased number of autophagosomes in both cell lines...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212395/delayed-apoptosis-allows-islet-%C3%AE-cells-to-implement-an-autophagic-mechanism-to-promote-cell-survival
#7
Heather L Hayes, Brett S Peterson, Jonathan M Haldeman, Christopher B Newgard, Hans E Hohmeier, Samuel B Stephens
Increased β-cell death coupled with the inability to replicate existing β-cells drives the decline in β-cell mass observed in the progression of both major forms of diabetes. Understanding endogenous mechanisms of islet cell survival could have considerable value for the development of novel strategies to limit β-cell loss and thereby promote β-cell recovery. Insulinoma cells have provided useful insight into β-cell death pathways but observations made in cell lines sometimes fail to translate to primary islets...
2017: PloS One
https://www.readbyqxmd.com/read/28211814/are-major-dementias-triggered-by-poor-blood-flow-to-the-brain-theoretical-considerations
#8
Jack C de la Torre
There is growing evidence that chronic brain hypoperfusion plays a central role in the development of Alzheimer's disease (AD) long before dyscognitive symptoms or amyloid-β accumulation in the brain appear. This commentary proposes that dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and Creutzfeldt-Jakob disease (CJD) may also develop from chronic brain hypoperfusion following a similar but not identical neurometabolic breakdown as AD. The argument to support this conclusion is that chronic brain hypoperfusion, which is found at the early stages of the three dementias reviewed here, will reduce oxygen delivery and lower oxidative phosphorylation promoting a steady decline in the synthesis of the cell energy fuel adenosine triphosphate (ATP)...
February 15, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28211011/teoa-a-triterpenoid-from-actinidia-eriantha-induces-autophagy-in-sw620-cells-via-endoplasmic-reticulum-stress-and-ros-dependent-mitophagy
#9
Dandan Zhang, Cuixia Gao, Ruyi Li, Lin Zhang, Jingkui Tian
2α,3α,24-Thrihydroxyurs-12-en-28-oicacid (TEOA), a pentacyclic triterpenoid, isolated from the roots of Actinidia eriantha, exhibits significant cytotoxicity against SW620, BGC-823, HepG-2, A549 and PC-3 cancer cells. In this study, we investigated the underlying molecular mechanism of the anticancer activity of TEOA in SW620 cells. We demonstrated that TEOA induced apoptosis through cleavage of caspase-9 and PARP in SW620 cells. In addition, evidence of TEOA-mediated autophagy included the induction of autophagolysosomes and activation of autophagic markers LC-3B and p62...
February 16, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28208686/identification-of-autophagy-related-genes-and-their-regulatory-mirnas-associated-with-celiac-disease-in-children
#10
Sergio Comincini, Federico Manai, Cristina Meazza, Sara Pagani, Carolina Martinelli, Noemi Pasqua, Gloria Pelizzo, Marco Biggiogera, Mauro Bozzola
Celiac disease (CD) is a severe genetic autoimmune disorder, affecting about one in 100 people, where the ingestion of gluten leads to damage in the small intestine. Diagnosing CD is quite complex and requires blood tests and intestinal biopsy examinations. Controversy exists regarding making the diagnosis without biopsy, due to the large spectrum of manifesting symptoms; furthermore, small-intestinal gastroscopy examinations have a relatively complex management in the pediatric population. To identify novel molecular markers useful to increase the sensitivity and specificity in the diagnosis of pediatric CD patients, the expression levels of two key autophagy executor genes (ATG7 and BECN1) and their regulatory validated miRNAs (miR-17 and miR-30a, respectively) were analyzed by relative quantitative real-time-PCR on a cohort of confirmed CD patients compared to age-related controls...
February 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28205624/the-small-molecule-auten-99-autophagy-enhancer-99-prevents-the-progression-of-neurodegenerative-symptoms
#11
Tibor Kovács, Viktor Billes, Marcell Komlós, Bernadette Hotzi, Anna Manzéger, Anna Tarnóci, Diána Papp, Fanni Szikszai, Janka Szinyákovics, Ákos Rácz, Béla Noszál, Szilvia Veszelka, Fruzsina R Walter, Mária A Deli, Laszlo Hackler, Robert Alfoldi, Orsolya Huzian, Laszlo G Puskas, Hanna Liliom, Krisztián Tárnok, Katalin Schlett, Adrienn Borsy, Ervin Welker, Attila L Kovács, Zsolt Pádár, Attila Erdős, Adam Legradi, Annamaria Bjelik, Károly Gulya, Balázs Gulyás, Tibor Vellai
Autophagy functions as a main route for the degradation of superfluous and damaged constituents of the cytoplasm. Defects in autophagy are implicated in the development of various age-dependent degenerative disorders such as cancer, neurodegeneration and tissue atrophy, and in accelerated aging. To promote basal levels of the process in pathological settings, we previously screened a small molecule library for novel autophagy-enhancing factors that inhibit the myotubularin-related phosphatase MTMR14/Jumpy, a negative regulator of autophagic membrane formation...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28202618/the-inflammatory-bowel-disease-associated-autophagy-gene-atg16l1t300a-acts-as-a-dominant-negative-variant-in-mice
#12
Ping Gao, Hongtao Liu, Huarong Huang, Qi Zhang, Warren Strober, Fuping Zhang
The basis of the increased risk for Crohn's disease conferred by the Atg16L1T300A polymorphism is incompletely understood. An important step forward came from the recent demonstration that the murine equivalent of Atg16L1T300A (Atg16L1T316A) exhibits increased susceptibility to caspase 3-mediated cleavage and resulting decreased levels of full-length Atg16L1 in macrophages. However, although this finding showed that this polymorphism is a loss-of-function abnormality, it did not address the possibility that this polymorphism also affects the function of a normal Atg16L1 allele in heterozygous mice...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28202616/dna-repair-interacts-with-autophagy-to-regulate-inflammatory-responses-to-pulmonary-hyperoxia
#13
Yan Ye, Ping Lin, Weidong Zhang, Shirui Tan, Xikun Zhou, Rongpeng Li, Qinqin Pu, Jonathan L Koff, Archana Dhasarathy, Feng Ma, Xin Deng, Jianxin Jiang, Min Wu
Oxygen is supplied as a supportive treatment for patients suffering from acute respiratory distress syndrome. Unfortunately, high oxygen concentration increases reactive oxygen species generation, which causes DNA damage and ultimately cell death in the lung. Although 8-oxoguanine-DNA glycosylase (OGG-1) is involved in repairing hyperoxia-mediated DNA damage, the underlying molecular mechanism remains elusive. In this study, we report that ogg-1-deficient mice exhibited a significant increase of proinflammatory cytokines (TNF-α, IL-6, and IFN-γ) in the lung after being exposed to 95% oxygen...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28198375/haploinsufficiency-networks-identify-targetable-patterns-of-allelic-deficiency-in-low-mutation-ovarian-cancer
#14
Joe Ryan Delaney, Chandni B Patel, Katelyn McCabe Willis, Mina Haghighiabyaneh, Joshua Axelrod, Isabelle Tancioni, Dan Lu, Jaidev Bapat, Shanique Young, Octavia Cadassou, Alena Bartakova, Parthiv Sheth, Carley Haft, Sandra Hui, Cheryl Saenz, David D Schlaepfer, Olivier Harismendy, Dwayne G Stupack
Identification of specific oncogenic gene changes has enabled the modern generation of targeted cancer therapeutics. In high-grade serous ovarian cancer (OV), the bulk of genetic changes is not somatic point mutations, but rather somatic copy-number alterations (SCNAs). The impact of SCNAs on tumour biology remains poorly understood. Here we build haploinsufficiency network analyses to identify which SCNA patterns are most disruptive in OV. Of all KEGG pathways (N=187), autophagy is the most significantly disrupted by coincident gene deletions...
February 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28197638/cobalt-chloride-treatment-induces-autophagic-apoptosis-in-human-glioma-cells-via-a-p53-dependent-pathway
#15
Bor-Chin Cheng, Jui-Tai Chen, Shun-Tai Yang, Chung-Ching Chio, Shing-Hwa Liu, Ruei-Ming Chen
Malignant glioma is the most aggressive brain tumor. Hypoxic condition has been explored for killing cancer stem cells or drug-resistant tumor cells. This study investigated the effects of hypoxia on autophagic death and the possible mechanisms. Exposure of human malignant glioma U87-MG cells to cobalt chloride (CoCl2) increased cellular hypoxia-inducible factor-1α levels and concurrently decreased cell viability concentration- and time-dependently. In parallel, treatment with CoCl2 suppressed proliferation of human U87-MG cells...
March 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28197628/resveratrol-induced-autophagy-and-apoptosis-in-cisplatin-resistant-human-oral-cancer-car-cells-a-key-role-of-ampk-and-akt-mtor-signaling
#16
Chao-Hsiang Chang, Chao-Ying Lee, Chi-Cheng Lu, Fuu-Jen Tsai, Yuan-Man Hsu, Je-Wei Tsao, Yu-Ning Juan, Hong-Yi Chiu, Jai-Sing Yang, Ching-Chiung Wang
Resveratrol is known to be an effective chemo-preventive phytochemical against multiple tumor cells. However, the increasing drug resistance avoids the cancer treatment in oral cavity cancer. In this study, we investigated the oral antitumor activity of resveratrol and its mechanism in cisplatin-resistant human oral cancer CAR cells. Our results demonstrated that resveratrol had an extremely low toxicity in normal oral cells and provoked autophagic cell death to form acidic vesicular organelles (AVOs) and autophagic vacuoles in CAR cells by acridine orange (AO) and monodansylcadaverine (MDC) staining...
March 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28197542/the-proline-arginine-dipeptide-from-hexanucleotide-repeat-expanded-c9orf72-inhibits-the-proteasome
#17
Rahul Gupta, Matthews Lan, Jelena Mojsilovic-Petrovic, Won Hoon Choi, Nathaniel Safren, Sami Barmada, Min Jae Lee, Robert Kalb
An intronic hexanucleotide repeat expansion (HRE) mutation in the C9ORF72 gene is the most common cause of familial ALS and frontotemporal dementia (FTD) and is found in ∼7% of individuals with apparently sporadic disease. Several different diamino acid peptides can be generated from the HRE by noncanonical translation (repeat-associated non-ATG translation, or RAN translation), and some of these peptides can be toxic. Here, we studied the effects of two arginine containing RAN translation products [proline/arginine repeated 20 times (PR20) and glycine/arginine repeated 20 times (GR20)] in primary rat spinal cord neuron cultures grown on an astrocyte feeder layer...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28197320/synthesis-biological-evaluation-and-autophagy-mechanism-of-12n-substituted-sophoridinamines-as-novel-anticancer-agents
#18
Chongwen Bi, Na Zhang, Peng Yang, Cheng Ye, Yanxiang Wang, Tianyun Fan, Rongguang Shao, Hongbin Deng, Danqing Song
A series of 12N-substituted sophoridinamine derivatives were synthesized and evaluated for their cytotoxic activities in human HepG2 hepatoma cells. Structure-activity relationship revealed that introduction of a suitable arylidene or arylethyl at the N'-end could greatly enhance antiproliferation potency. Among them, compound 6b possessing a N'-trimethoxyphenyl methylene exhibited potent antiproliferation effect against three human tumor cell lines including HepG2, leukemia (K562), and breast cancer (HMLE), with IC50 between 0...
February 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28195671/trachycladines-and-analogues-synthesis-and-anti-cancer-activity-evaluation
#19
Zisis V Peitsinis, Achilleas G Mitrakas, Eirini A Nakiou, Dafni A Melidou, Dimitra Kalamida, Christos Kakouratos, Michael I Koukourakis, Alexandros E Koumbis
The synthesis of four new analogues of marine nucleoside trachycladine A was accomplished via direct regio- and stereoselective Vorbrüggen glycosylations of 2,6-dichloropurine and 2-chloropurine with a D-ribose derived chiron. Naturally occurring trachycladines (A and B) and a series of analogues were examined for their cytotoxic activity against a number of cancer cell lines (glioblastoma, lung and cervical cancer). Parent trachycladine A and two analogues (the diacetate of 2,6-dichloropurine derivative and N-cyclopropyl trachycladine A) were found to result in a significant reduction of cell viability, with the latter exhibiting a stronger effect...
February 14, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28195184/new-findings-of-silica-nanoparticles-induced-er-autophagy-in-human-colon-cancer-cell
#20
Fujing Wei, Yimin Wang, Zewei Luo, Yu Li, Yixiang Duan
Nanoparticle-induced autophagy has been extensively studied, however, real time information about the endoplasmic reticulum involved autophagic process (ER autophagy) induced by nanomaterials remains unknown. In this work, silica nanoparticles (SNPs) were synthesized with characteristics of low toxicity, good biocompatibility and excellent water dispersibility to treat cells. Results show that either low concentration (10 μg/mL) or high concentration (200 μg/mL) of SNPs could increase the quantity of processing from microtubule-associated protein 1-light chain 3-I (LC3-I) to the other variant of LC3 (LC3-II)...
February 14, 2017: Scientific Reports
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