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https://www.readbyqxmd.com/read/28431575/heterogeneous-ribonuclear-protein-a3-hnrnp-a3-is-present-in-dipeptide-repeat-protein-containing-inclusions-in-frontotemporal-lobar-degeneration-and-motor-neurone-disease-associated-with-expansions-in-c9orf72-gene
#1
Yvonne S Davidson, Louis Flood, Andrew C Robinson, Yoshihiro Nihei, Kohji Mori, Sara Rollinson, Anna Richardson, Bridget C Benson, Matthew Jones, Julie S Snowden, Stuart Pickering-Brown, Christian Haass, Tammaryn Lashley, David M A Mann
Frontotemporal Lobar Degeneration (FTLD) encompasses certain related neurodegenerative disorders which alter behaviour, personality and language. Heterogeneous ribonuclear proteins (hnRNPs) maintain RNA metabolism and changes in their function may underpin the pathogenesis of FTLD. Immunostaining for hnRNP A1, A2/B1 and A3 was performed on sections of temporal cortex with hippocampus from 61 patients with FTLD, stratified by pathological hallmarks into FTLD-tau and FTLD-TDP type A, B and C subtypes, and by genetics into patients with C9orf72 expansions, MAPT or GRN mutations, or those without known mutation...
April 21, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28431282/the-role-of-pharmacologic-modulation-of-autophagy-on-anal-cancer-development-in-an-hpv-mouse-model-of-carcinogenesis
#2
Brooks L Rademacher, Kristina A Matkowskyj, Louise M Meske, Alexis Romero, Hana Sleiman, Evie H Carchman
Autophagy is an intracellular, catabolic process that maintains cellular health. We examined the response of pharmacologic modulation of autophagy in an HPV mouse model of anal carcinogenesis. K14E6/E7 mice were treated with the topical carcinogen DMBA weekly and assessed for tumors over 20 weeks. Concurrently, they were given either chloroquine or BEZ235, to inhibit or induce autophagy, respectively. Time to tumor onset was examined. Immunofluorescence (IF) was performed for LC3β and p62 to examine autophagy...
April 18, 2017: Virology
https://www.readbyqxmd.com/read/28429767/love-laughs-at-locksmiths-ubiquitylation-of-p62-sequestosome-1-unlocks-its-autophagy-receptor-potential
#3
Owen Conway, Vladimir Kirkin
The multimodular adapter p62/sequestosome-1 plays prominent roles in physiology and disease by mediating cell signaling and cargo degradation. The work by Peng et al. published recently in Cell Research provides mechanistic insights into activation of its autophagy receptor function critical for maintaining cell homeostasis during various forms of stress.
April 21, 2017: Cell Research
https://www.readbyqxmd.com/read/28429406/haplodeficiency-of-cathepsin-d-does-not-affect-cerebral-amyloidosis-and-autophagy-in-app-ps1-transgenic-mice
#4
Shaowu Cheng, Willayat Y Wani, David A Hottman, Angela Jeong, Dongfeng Cao, Kyle J LeBlanc, Paul Saftig, Jianhua Zhang, Ling Li
Autophagy and lysosomal function are important for protein homeostasis and their dysfunction have been associated with Alzheimer's disease (AD). Increased immunoreactivities of an important lysosomal protease, cathepsin D (Cat D), are evident in amyloid plaques and neurons in patients with AD. The current study tests the hypothesis that deleting one allele of the cathepsin D gene (Ctsd) impacts cerebral β-amyloidosis in APPsw/PS1dE9 (APP/PS1) double transgenic mice. Despite a significant 38% decrease of Cat D level in APP/PS1/Ctsd+/- compared to APP/PS1/Ctsd+/+ mice, no changes in steady state levels and deposition of Aβ were found in the brain...
April 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28428777/lactobacillus-fermentum-postbiotic-induced-autophagy-as-potential-approach-for-treatment-of-acetaminophen-hepatotoxicity
#5
Miroslav Dinić, Jovanka Lukić, Jelena Djokić, Marina Milenković, Ivana Strahinić, Nataša Golić, Jelena Begović
The aim of this study was to investigate the potential of postbiotics originated from Lactobacillus fermentum BGHV110 strain (HV110) to counteract acetaminophen (APAP)-induced hepatotoxicity in HepG2 cells. This strain was selected according to its autophagy inducing potential, based on previous studies reporting protective role of autophagy in APAP caused cellular damage. Cell viability was assessed using MTT and LDH assays, while autophagy was monitored by qPCR analysis of BECN1, Atg5, p62/SQSTM1, and PINK1 mRNA expression and by Western blot analysis of p62/SQSTM1 and lipidated LC3 accumulation...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28428740/protein-quality-control-by-molecular-chaperones-in-neurodegeneration
#6
REVIEW
Aaron Ciechanover, Yong Tae Kwon
Protein homeostasis (proteostasis) requires the timely degradation of misfolded proteins and their aggregates by protein quality control (PQC), of which molecular chaperones are an essential component. Compared with other cell types, PQC in neurons is particularly challenging because they have a unique cellular structure with long extensions. Making it worse, neurons are postmitotic, i.e., cannot dilute toxic substances by division, and, thus, are highly sensitive to misfolded proteins, especially as they age...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28427080/rapamycin-induces-autophagy-and-reduces-the-apoptosis-of-podocytes-under-a-stimulated-condition-of-immunoglobulin-a-nephropathy
#7
Shikai Liang, Juan Jin, Bo Lin, Jianguang Gong, Yiwen Li, Qiang He
Backgroud/Aims: The aim of this study was to investigate the potential renoprotective effect of rapamycin on the autophagy of podocytes treated with the supernatant of mesangial cells cultured with aggregated IgA1 (aIgA1) from immunoglobulin A nephropathy (IgAN) patients. METHODS: Monomeric IgA1 (mIgA1) was isolated from the serum of IgAN patients or healthy volunteers, and then transformed to aIgA1 by heating. Subsequently, the aIgA1-mesangial cell supernatant was prepared by collecting the medium of mouse mesangial cells (MSC1097) cultured with aIgA1 (100 mg/L) from different IgAN patients or healthy volunteers for 48 h...
April 18, 2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/28424968/visualization-of-reticulophagy-in-living-cells-using-an-endoplasmic-reticulum-targeted-p62-mutant
#8
Liang Wang, Lei Liu, Lingsong Qin, Qingming Luo, Zhihong Zhang
Reticulophagy is a type of selective autophagy in which protein aggregate-containing and/or damaged endoplasmic reticulum (ER) fragments are engulfed for lysosomal degradation, which is important for ER homeostasis. Several chemical drugs and mutant proteins that promote protein aggregate formation within the ER lumen can efficiently induce reticulophagy in mammalian cells. However, the exact mechanism and cellular localization of reticulophagy remain unclear. In this report, we took advantage of the self-oligomerization property of p62/SQSTM1, an adaptor for selective autophagy, and developed a novel reticulophagy system based on an ER-targeted p62 mutant to investigate the process of reticulophagy in living cells...
April 13, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28424277/janus-kinase-2-regulates-transcription-factor-eb-expression-and-autophagy-completion-in-glomerular-podocytes
#9
Tamadher A Alghamdi, Syamantak Majumder, Karina Thieme, Sri N Batchu, Kathryn E White, Youan Liu, Angela S Brijmohan, Bridgit B Bowskill, Suzanne L Advani, Minna Woo, Andrew Advani
The nonreceptor kinase Janus kinase 2 (JAK2) has garnered attention as a promising therapeutic target for the treatment of CKD. However, being ubiquitously expressed in the adult, JAK2 is also likely to be necessary for normal organ function. Here, we investigated the phenotypic effects of JAK2 deficiency. Mice in which JAK2 had been deleted from podocytes exhibited an elevation in urine albumin excretion that was accompanied by increased podocyte autophagosome fractional volume and p62 aggregation, which are indicative of impaired autophagy completion...
April 19, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28423647/upregulation-of-the-lncrna-meg3-induces-autophagy-to-inhibit-tumorigenesis-and-progression-of-epithelial-ovarian-carcinoma-by-regulating-activity-of-atg3
#10
Yin-Ling Xiu, Kai-Xuan Sun, Xi Chen, Shuo Chen, Yang Zhao, Qing-Guo Guo, Zhi-Hong Zong
Maternally expressed gene 3 (Meg3), a long non-coding RNA, has been reported to be associated with the pathogenesis of multiple malignancies. However, little is known regarding the role of Meg3 in epithelial ovarian cancer (EOC). In this study, we found that the expression of Meg3 was lower in epithelial ovarian carcinoma, and has potential to be considered as a biomarker for ovarian cancer. After transfecting the ovarian cancer cell lines OVCAR3 and A2780 with Meg3, phenotypic changes and autophagy-related molecules were examined...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423083/autophagy-protects-against-neural-cell-death-induced-by-piperidine-alkaloids-present-in-prosopis-juliflora-mesquite
#11
Victor D A Silva, Carlos Cuevas, Patricia Muñoz, Monica Villa, Ulises Ahumada-Castro, Sandro Huenchuguala, Cleonice C Dos Santos, Fillipe M DE Araujo, Rafael S Ferreira, Vanessa B DA Silva, Juliana H C E Silva, Érica N Soares, Eudes S Velozo, Juan Segura-Aguilar, Silvia L Costa
Prosopis juliflora is a shrub that has been used to feed animals and humans. However, a synergistic action of piperidine alkaloids has been suggested to be responsible for neurotoxic damage observed in animals. We investigated the involvement of programmed cell death (PCD) and autophagy on the mechanism of cell death induced by a total extract (TAE) of alkaloids and fraction (F32) from P. juliflora leaves composed majoritary of juliprosopine in a model of neuron/glial cell co-culture. We saw that TAE (30 µg/mL) and F32 (7...
January 2017: Anais da Academia Brasileira de Ciências
https://www.readbyqxmd.com/read/28422956/chronic-activation-of-ppar%C3%AE-with-fenofibrate-reduces-autophagic-proteins-in-the-liver-of-mice-independent-of-fgf21
#12
Eunjung Jo, Songpei Li, Qingning Liang, Xinmei Zhang, Hao Wang, Terence P Herbert, Trisha A Jenkins, Aimin Xu, Ji-Ming Ye
Autophagy is a catabolic mechanism to degrade cellular components to maintain cellular energy levels during starvation, a condition where PPARα may be activated. Here we report a reduced autophagic capacity in the liver following chronic activation of PPARα with fenofibrate (FB) in mice. Chronic administration of the PPARα agonist FB substantially reduced the levels of multiple autophagy proteins in the liver (Atg3, Agt4B, Atg5, Atg7 and beclin 1) which were associated with a decrease in the light chain LC3II/LC3I ratio and the accumulation of p62...
2017: PloS One
https://www.readbyqxmd.com/read/28421659/the-anti-inflammatory-effects-of-morin-hydrate-in-atherosclerosis-is-associated-with-autophagy-induction-through-camp-signaling
#13
Yue Zhou, Zhan-Qi Cao, Hong-Yuan Wang, Yan-Na Cheng, Lu-Gang Yu, Xin-Ke Zhang, Yan Sun, Xiu-Li Guo
SCOPE: Although the previous trials of inflammation have indicated that morin hydrate (MO) hold considerable promise, understanding the distinct mechanism of MO against inflammation remains a challenge. METHODS AND RESULTS: This study investigated the effect of MO in atherosclerosis in ApoE(-/-) mice and underlying cell signaling of MO effect in inflammation in human umbilical vein endothelial cells (HUVECs). Administration of MO significantly reduced serum lipid level, inflammatory cytokines (TNF-α and ICAM-1) and atherosclerotic plaque formation in vivo...
April 18, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28421304/increased-autophagic-degradation-contributes-to-the-neuroprotection-of-hydrogen-sulfide-against-cerebral-ischemia-reperfusion-injury
#14
Yuanjun Zhu, Mengyang Shui, Xiaoyan Liu, Wenhui Hu, Yinye Wang
Hydrogen sulfide (H2S), an endogenous gaseous signal molecule, exhibits protective effect against ischemic injury. However, its underlying mechanism is not fully understood. We have recently reported that exogenous H2S decreases the accumulation of autophagic vacuoles in mouse brain with ischemia/reperfusion (I/R) injury. To further investigate whether this H2S-induced reduction of autophagic vacuoles is caused by the decreased autophagosome synthesis and/or the increased autophagic degradation inautophagic flux, we performed in vitro and in vivo studies using SH-SY5Y cells for the oxygen and glucose deprivation/reoxygenation (OGD/R) and mice for the cerebral I/R, respectively...
April 18, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28420993/phellinus-linteus-mycelium-alleviates-myocardial-ischemia-reperfusion-injury-through-autophagic-regulation
#15
Hsing-Hui Su, Ya-Chun Chu, Jiuan-Miaw Liao, Yi-Hsin Wang, Ming-Shiou Jan, Chia-Wei Lin, Chiu-Yeh Wu, Chin-Yin Tseng, Jiin-Cherng Yen, Shiang-Suo Huang
The incidence of myocardial ischemia-reperfusion (IR) injury is rapidly increasing around the world and this disease is a major contributor to global morbidity and mortality. It is known that regulation of programmed cell death including apoptosis and autophagy reduces the impact of myocardial IR injury. In this study, the cardioprotective effects and underlying mechanisms of Phellinus linteus (Berk. and Curt.) Teng, Hymenochaetaceae (PL), a type of medicinal mushroom, were examined in rats subjected to myocardial IR injury...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28420820/high-insulin-impaired-ovarian-function-in-early-pregnant-mice-and-the-role-of-autophagy-in-this-process
#16
Yan Su, Juan Wu, Junlin He, Xueqing Liu, Xuemei Chen, Yubin Ding, Chen Zhang, Wenqi Chen, Yingxiong Wang, Rufei Gao
Metabolic disorders, such as PCOS (polycystic ovarian syndrome) and T2DM (type 2 diabetes mellitus), are associated with menstrual dysfunction, anovulation, infertility, and early pregnancy loss. Ovarian dysfunction is not only related to low pregnancy rates but also to the increased risk of miscarriage. Women with PCOS or T2DM, characterized by hyperinsulinemia, commonly experience ovarian dysfunction. In this study, we first explored whether high insulin levels directly affected ovarian functioning during embryo implantation...
April 18, 2017: Endocrine Journal
https://www.readbyqxmd.com/read/28419832/dihydromyricetin-modulates-p62-and-autophagy-crosstalk-with-the-keap-1-nrf2-pathway-to-alleviate-ethanol-induced-hepatic-injury
#17
Ping Qiu, Yu Dong, Bo Li, Xian-Jie Kang, Chao Gu, Tao Zhu, Yun-Yun Luo, Min-Xia Pang, Wei-Feng Du, Wei-Hong Ge
Increasing evidence has demonstrated that dihydromyricetin (DMY) contains highly effective antioxidative, anti-inflammatory, anti-microbial and anti-diabetic properties. Nevertheless, the underlying hepatoprotective mechanisms of DMY have infrequently been reported thus far. In the present study, C57BL/6 mice were fed with the Lieber-DeCarli diet containing alcohol or isocaloric maltose dextrin as a control diet with or without DMY (75 and 150mg/kg/d bw) for 6 weeks. DMY significantly attenuated hepatic enzyme release, hepatic lipid peroxidation and triglyceride deposition induced by chronic alcohol exposure...
April 15, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28409281/spinal-poly-ga-inclusions-in-a-c9orf72-mouse-model-trigger-motor-deficits-and-inflammation-without-neuron-loss
#18
Martin H Schludi, Lore Becker, Lillian Garrett, Tania F Gendron, Qihui Zhou, Franziska Schreiber, Bastian Popper, Leda Dimou, Tim M Strom, Juliane Winkelmann, Anne von Thaden, Kristin Rentzsch, Stephanie May, Meike Michaelsen, Benjamin M Schwenk, Jing Tan, Benedikt Schoser, Marianne Dieterich, Leonard Petrucelli, Sabine M Hölter, Wolfgang Wurst, Helmut Fuchs, Valerie Gailus-Durner, Martin Hrabe de Angelis, Thomas Klopstock, Thomas Arzberger, Dieter Edbauer
Translation of the expanded (ggggcc)n repeat in C9orf72 patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) causes abundant poly-GA inclusions. To elucidate their role in pathogenesis, we generated transgenic mice expressing codon-modified (GA)149 conjugated with cyan fluorescent protein (CFP). Transgenic mice progressively developed poly-GA inclusions predominantly in motoneurons and interneurons of the spinal cord and brain stem and in deep cerebellar nuclei. Poly-GA co-aggregated with p62, Rad23b and the newly identified Mlf2, in both mouse and patient samples...
April 13, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28406179/genetic-visualization-of-protein-interactions-harnessing-liquid-phase-transitions
#19
Taku Watanabe, Tatsuya Seki, Takashi Fukano, Asako Sakaue-Sawano, Satoshi Karasawa, Misaki Kubota, Hiroshi Kurokawa, Ken Inoue, Junichi Akatsuka, Atsushi Miyawaki
Protein-protein interactions (PPIs) are essential components of cellular function. Current fluorescence-based technologies to measure PPIs have limited dynamic range and quantitative reproducibility. Here, we describe a genetically-encoded PPI visualization system that harnesses the dynamics of condensed liquid-phase transitions to analyze protein interactions in living cells. The fluorescent protein Azami-Green and p62-PB1 domain when fused to PPI partners triggered a rapid concatenation/oligomerization process that drove the condensation of liquid-phase droplets for real-time analysis of the interaction with unlimited dynamic range in the fluorescence signal...
April 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28405513/tumor-sqstm1-p62-expression-and-t-cells-in-colorectal-cancer
#20
Keisuke Kosumi, Yohei Masugi, Juhong Yang, Zhi Rong Qian, Sun A Kim, Wanwan Li, Yan Shi, Annacarolina da Silva, Tsuyoshi Hamada, Li Liu, Mancang Gu, Tyler S Twombly, Yin Cao, David A Barbie, Katsuhiko Nosho, Hideo Baba, Wendy S Garrett, Jeffery A Meyerhardt, Edward L Giovannucci, Andrew T Chan, Charles S Fuchs, Shuji Ogino, Reiko Nishihara
Evidence suggests that activation of autophagy in neoplastic cells potentiates antitumor immunity through cross-presentation of tumor-associated antigens to T cells and release of immune mediators. The SQSTM1 (sequestosome 1, p62) protein is degraded by activated autophagy, and might enhance immune response to tumor cells. We hypothesized that tumor SQSTM1 expression level might be inversely associated with T-cell densities in colorectal carcinoma tissue. We evaluated tumor SQSTM1 expression by immunohistochemistry in 601 rectal and colon cancer cases within the Nurses' Health Study and Health Professionals Follow-up Study...
2017: Oncoimmunology
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