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endoplasmic reticulum and autophagy

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https://www.readbyqxmd.com/read/28915631/in-vivo-autophagy-and-biogenesis-of-autophagosomes-within-male-haploid-cells-during-spermiogenesis
#1
Ping Yang, Nisar Ahmed, Lingling Wang, Hong Chen, Yasir Waqas, Tengfei Liu, Abdul Haseeb, Nasrullah Bangulzai, Yufei Huang, Qiusheng Chen
Autophagy is a unique catabolic pathway that is linked to several physiological processes. However, its role in the process of spermiogenesis is largely unknown. The aim of the current study was to determine the in vivo role of autophagy and the origin of autophagosome membrane biogenesis within male haploid cells. Our immunohistochemistry results demonstrated that LC3 and ATG7 localization were increased dramatically in round to elongated spermatids (haploid cells) towards the lumen of seminiferous tubules, however, poorly expressed in the early stages of germ cells near the basal membrane...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28906486/small-molecule-rl71-triggered-excessive-autophagic-cell-death-as-a-potential-therapeutic-strategy-in-triple-negative-breast-cancer
#2
Jian Gao, Minmin Fan, Shuang Peng, Minxia Zhang, Gang Xiang, Xin Li, Wenjie Guo, Yang Sun, Xuefeng Wu, Xudong Wu, Guang Liang, Yan Shen, Qiang Xu
Triple-negative breast cancer (TNBC) has an aggressive phenotype and a poor prognosis owing to the high propensity for metastatic progression and the absence of specific targeted treatment. Here, we revealed that small-molecule RL71 targeting sarco/endoplasmic reticulum calcium-ATPase 2 (SERCA2) exhibited potent anti-cancer activity on all TNBC cells tested. Apart from apoptosis induction, RL71 triggered excessive autophagic cell death, the main contributor to RL71-induced TNBC cell death. RL71 augmented the release of Ca(2+) from the endoplasmic reticulum (ER) into the cytosol by inhibiting SERCA2 activity...
September 14, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28904818/nf-%C3%AE%C2%BAb-pathway-link-with-er-stress-induced-autophagy-and-apoptosis-in-cervical-tumor-cells
#3
Xiaolan Zhu, Li Huang, Jie Gong, Chun Shi, Zhiming Wang, Bingkun Ye, Aiguo Xuan, Xiaosong He, Dahong Long, Xiao Zhu, Ningfang Ma, Shuilong Leng
Targeting endoplasmic reticulum (ER) stress is being investigated for its anticancer effect in various cancers, including cervical cancer. However, the molecular pathways whereby ER stress mediates cell death remain to be fully elucidated. In this study, we confirmed that ER stress triggered by compounds such as brefeldin A (BFA), tunicamycin (TM), and thapsigargin (TG) leads to the induction of the unfolded protein response (UPR) in cervical cancer cell lines, which is characterized by elevated levels of inositol-requiring kinase 1α, glucose-regulated protein-78, and C/EBP homologous protein, and swelling of the ER observed by transmission electron microscope (TEM)...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28904211/zonda-is-a-novel-early-component-of-the-autophagy-pathway-in-drosophila
#4
Mariana Melani, Ayelén Valko, Nuria M Romero, Milton O Aguilera, Julieta M Acevedo, Zambarlal Bhujabal, Joel Perez-Perri, Rocío V de la Riva-Carrasco, Maximiliano J Katz, Eleonora Sorianello, Cecilia D'Alessio, Gabor Juhász, Terje Johansen, María I Colombo, Pablo Wappner
Autophagy is an evolutionary conserved process by which eukaryotic cells undergo self-digestion of cytoplasmic components. Here we report that a novel Drosophila immunophilin, which we have named Zonda, is critically required for starvation-induced autophagy. We show that Zonda operates at early stages of the process, specifically for Vps34-mediated phosphatidylinositol 3-phosphate (PI3P) deposition. Zonda displays an even distribution under basal conditions, and soon after starvation nucleates in endoplasmic reticulum-associated foci that colocalize with omegasome markers...
September 13, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28903070/role-of-the-ampk-pathway-in-promoting-autophagic-flux-via-modulating-mitochondrial-dynamics-in-neurodegenerative-diseases-insight-into-prion-diseases
#5
REVIEW
Syed Zahid Ali Shah, Deming Zhao, Tariq Hussain, Lifeng Yang
Neurons are highly energy demanding cells dependent on the mitochondrial oxidative phosphorylation system. Mitochondria generate energy via respiratory complexes that constitute the electron transport chain. Adenosine triphosphate depletion or glucose starvation act as a trigger for the activation of adenosine monophosphate-activated protein kinase (AMPK). AMPK is an evolutionarily conserved protein that plays an important role in cell survival and organismal longevity through modulation of energy homeostasis and autophagy...
September 10, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28901440/autophagy-and-er-stress-in-lps-galn%C3%A2-induced-acute-liver-injury
#6
Ting Shi, Weifang Song, Ruiling Xu
Numerous mechanisms and factors have been implicated in liver damage; however, the involvement of autophagy and endoplasmic reticulum (ER) stress during early‑stage liver injury remains to be fully elucidated. The present study was conducted to determine the expression of autophagy and ER‑stress‑associated proteins in hepatic tissues following injury. A murine model of liver injury was induced by intraperitoneally injecting lipopolysaccharide (LPS) and D‑galactosamine (GalN), and control mice were similarly injected with normal saline...
August 31, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28900935/metabolic-disorders-and-cancer-hepatocyte-store-operated-ca-2-channels-in-nonalcoholic-fatty-liver-disease
#7
Eunüs S Ali, Grigori Y Rychkov, Greg J Barritt
In steatotic hepatocytes, intracellular Ca(2+) homeostasis is substantially altered compared to normal. Decreased Ca(2+) in the endoplasmic reticulum (ER) can lead to ER stress, an important mediator of the progression of liver steatosis to nonalcoholic steatohepatitis, type 2 diabetes, and hepatocellular carcinoma. Store-operated Ca(2+) channels (SOCs) in hepatocytes are composed principally of Orai1 and STIM1 proteins. Their main role is the maintenance of adequate Ca(2+) in the lumen of the ER. In steatotic hepatocytes, store-operated Ca(2+) entry (SOCE) is substantially inhibited...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28899653/role-of-autophagy-in-zika-virus-infection-and-pathogenesis
#8
REVIEW
Abhilash I Chiramel, Sonja M Best
Autophagy is an evolutionarily conserved cellular pathway that culminates in lysosomal degradation of selected substrates. Autophagy can serve dual roles in virus infection with either pro- or antiviral functions depending on the virus and the stage of the viral replication cycle. Recent studies have suggested a role for autophagy in Zika virus (ZIKV) replication by demonstrating the accumulation of autophagic vesicles following ZIKV infection in both in vitro and in vivo models. In human fetal neural stem cells, ZIKV inhibits Akt-mTOR signaling to induce autophagy, increase virus replication and impede neurogenesis...
September 9, 2017: Virus Research
https://www.readbyqxmd.com/read/28888852/renal-endoplasmic-reticulum-stress-is-coupled-to-impaired-autophagy-in-a-mouse-model-of-gsd-ia
#9
Benjamin L Farah, Dustin J Landau, Yajun Wu, Rohit A Sinha, Alwin Loh, Boon-Huat Bay, Dwight D Koeberl, Paul M Yen
GSD Ia (von Gierke Disease, Glycogen Storage Disease Type Ia) is a devastating genetic disorder with long-term sequelae, such as non-alcoholic fatty liver disease and renal failure. Down-regulated autophagy is involved in the development of hepatic metabolic dysfunction in GSD Ia; however, the role of autophagy in the renal pathology is unknown. Here we show that autophagy is impaired and endoplasmic reticulum (ER) stress is increased in the kidneys of a mouse model of GSD Ia. Induction of autophagy by rapamycin also reduces this ER stress...
September 1, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28870808/hedgehog-signaling-inhibitor-gant61-induces-endoplasmic-reticulum-stress-mediated-protective-autophagy-in-hepatic-stellate-cells
#10
Jie Li, Lingmin Zhang, Qingqing Xia, Junhui Fu, Zhijun Zhou, Feng Lin
Hedgehog (Hh) signaling plays an important role in the viability maintenance of hepatic stellate cells (HSC). HSCs have been identified as the major profibrogenic cells in the liver. The present study revealed that a novel Hh antagonist GANT61 induced apoptosis in the activated human hepatic stellate cell line LX-2 cells, as it dose-dependently caused mitochondrial inner transmembrane potential (ΔΨm) loss and caspase-3 cleavage. Autophagic flux was markedly increased after GANT61 treatment in LX-2 cells...
September 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28868254/mitochondria-associated-membranes-as-networking-platforms-and-regulators-of-cancer-cell-fate
#11
REVIEW
Maria Livia Sassano, Alexander R van Vliet, Patrizia Agostinis
The tight cross talk between two essential organelles of the cell, the endoplasmic reticulum (ER) and mitochondria, is spatially and functionally regulated by specific microdomains known as the mitochondria-associated membranes (MAMs). MAMs are hot spots of Ca(2+) transfer between the ER and mitochondria, and emerging data indicate their vital role in the regulation of fundamental physiological processes, chief among them mitochondria bioenergetics, proteostasis, cell death, and autophagy. Moreover, and perhaps not surprisingly, it has become clear that signaling events regulated at the ER-mitochondria intersection regulate key processes in oncogenesis and in the response of cancer cells to therapeutics...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28865110/the-effect-of-photodamage-on-the-female-caucasian-facial-stratum-corneum-corneome-using-mass-spectrometry-based-proteomics
#12
Rainer Voegeli, Jean-Marc Monneuse, Rotraut Schoop, Beverley Summers, Anthony V Rawlings
BACKGROUND: The effect of photodamage on facial stratum corneum (SC) is still poorly understood. OBJECTIVE: To describe the SC proteome from tape strippings of Caucasian SC from photoexposed cheek and photoprotected post auricular (PA) site a global analysis of photodamage on the skin will be developed leading to a better understanding of keratinocyte signalling pathways and identification of new molecular targets for the treatment of photoaged skin. METHODS: Female Caucasian subjects had 9 consecutive tape strippings taken from their cheeks and PA site...
September 2, 2017: International Journal of Cosmetic Science
https://www.readbyqxmd.com/read/28864006/endoplasmic-reticulum-stress-responses-in-placentation-a-true-balancing-act
#13
Daniel Bastida-Ruiz, Elizabeth Aguilar, Agnès Ditisheim, Lucile Yart, Marie Cohen
The unfolded protein response (UPR) is recognized as a key mechanism to promote protein folding and processing in eukaryotes when endoplasmic reticulum stress (ERS) occurs. Some conditions such as hypoxia or glucose deprivation are factors that may elicit ERS response. Recent literature collectively proposes that ERS response is crucial for mammalian reproduction by allowing decidualization and placentation to occur. However, prolonged ERS and activation of UPR pathways can lead to apoptosis and autophagy, which in turn could pose adverse effects on pregnancy outcomes and placentation...
September 2017: Placenta
https://www.readbyqxmd.com/read/28859319/autophagy-participates-in-the-unfolded-protein-response-in-toxoplasma-gondii
#14
Hoa Mai Nguyen, Laurence Berry, William J Sullivan, Sébastien Besteiro
Environmental and genetic perturbations of endoplasmic reticulum (ER) function can lead to the accumulation of unfolded proteins. In these conditions, eukaryotic cells can activate a complex signaling network called the unfolded protein response (UPR) to reduce ER stress and restore cellular homeostasis. Autophagy, a degradation and recycling process, is part of this response. The parasitic protist Toxoplasma gondii is known to be able to activate the UPR upon ER stress, and we now show that this pathway leads to autophagy activation, supporting the idea of a regulated function for canonical autophagy as part of an integrated stress response in the parasites...
August 15, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/28842527/mechanisms-contributing-to-cardiac-remodelling
#15
REVIEW
Qing-Qing Wu, Yang Xiao, Yuan Yuan, Zhen-Guo Ma, Hai-Han Liao, Chen Liu, Jin-Xiu Zhu, Zheng Yang, Wei Deng, Qi-Zhu Tang
Cardiac remodelling is classified as physiological (in response to growth, exercise and pregnancy) or pathological (in response to inflammation, ischaemia, ischaemia/reperfusion (I/R) injury, biomechanical stress, excess neurohormonal activation and excess afterload). Physiological remodelling of the heart is characterized by a fine-tuned and orchestrated process of beneficial adaptations. Pathological cardiac remodelling is the process of structural and functional changes in the left ventricle (LV) in response to internal or external cardiovascular damage or influence by pathogenic risk factors, and is a precursor of clinical heart failure (HF)...
September 15, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28842428/defective-lysosomal-clearance-of-autophagosomes-and-its-clinical-implications-in-nonalcoholic-steatohepatitis
#16
Xiaojuan Wang, Xiang Zhang, Eagle S H Chu, Xiaoting Chen, Wei Kang, Feng Wu, Ka-Fai To, Vincent W S Wong, Henry L Y Chan, Matthew T V Chan, Joseph J Y Sung, William K K Wu, Jun Yu
Autophagic impairment is implicated in nonalcoholic fatty liver disease (NAFLD), but the molecular mechanism is unclear. We found that autophagic flux was significantly inhibited in 3 murine models of NAFLD. Interestingly, the number of acidic organelles and the level of mature cathepsin D were reduced, suggesting defective lysosome acidification. Asparagine synthetase (ASNS) was induced by endoplasmic reticulum stress, leading to the generation of asparagine, which inhibited lysosome acidification. Both steatotic- and asparagine-treated hepatocytes showed reduced lysosomal acidity and retention of lysosomal calcium...
August 25, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28841673/chop-favors-endoplasmic-reticulum-stress-induced-apoptosis-in-hepatocellular-carcinoma-cells-via-inhibition-of-autophagy
#17
Yan Lei, Shuiliang Wang, Bingshuang Ren, Jin Wang, Jin Chen, Jun Lu, Shihuai Zhan, Yunfeng Fu, Lianghu Huang, Jianming Tan
C/EBP-homologous protein (CHOP) is an important component of the endoplasmic reticulum (ER) stress response. We demonstrated the induction of ER stress in response to tunicamycin stimulation, as evidenced by increased expression of chaperone proteins Grp78, Grp94, and enhanced eukaryotic initiation factor 2 subunit 1 (eIF2α) phosphorylation in hepatocellular carcinoma cells. Tunicamycin-induced ER stress resulted in apoptosis and autophagy simultaneously. While inhibition of autophagy mediated by 3-methyladenine pretreatment or direct knockdown of LC3B promoted cell apoptosis, activation of autophagy with rapamycin decreased tunicamycin- induced apoptosis in HCC cells...
2017: PloS One
https://www.readbyqxmd.com/read/28838965/blocking-autophagy-enhances-the-pro-apoptotic-effect-of-bufalin-on-human-gastric-cancer-cells-through-endoplasmic-reticulum-stress
#18
Hongyan Zhao, Qinghua Li, Jie Pang, Huilin Jin, Hongwei Li, Xiaoying Yang
Bufalin has been used to treat cancer for several years. However, the molecular mechanisms for its anti-tumor function are not fully understood. This work aimed to investigate the effect of bufalin on the proliferation and apoptosis of human gastric cancer (HGC) cells and the roles of endoplasmic reticulum (ER) stress and autophagy in bufalin induced apoptosis. HGC cell lines, SGC7901 and BGC823 were treated with different concentration of bufalin or 80 nmol/l bufalin for 1, 2, 3 and 4 days. Cell counting kit-8 (CCK-8) assay and direct cell counting method were used to detect proliferation...
August 24, 2017: Biology Open
https://www.readbyqxmd.com/read/28817690/resveratrol-and-caloric-restriction-prevent-hepatic-steatosis-by-regulating-sirt1-autophagy-pathway-and-alleviating-endoplasmic-reticulum-stress-in-high-fat-diet-fed-rats
#19
Shibin Ding, Jinjin Jiang, Guofu Zhang, Yongjun Bu, Guanghui Zhang, Xiangmei Zhao
BACKGROUND: Studies have demonstrated that resveratrol (a natural polyphenol) and caloric restriction activate Sirtuin-1 (SIRT1) and induce autophagy. Furthermore, autophagy is induced by the SIRT1-FoxO signaling pathway and was recently shown to be a critical protective mechanism against non-alcoholic fatty liver disease (NAFLD) development. We aimed to compare the effects of resveratrol and caloric restriction on hepatic lipid metabolism and elucidate the mechanism by which resveratrol supplementation and caloric restriction alleviate hepatosteatosis by examining the molecular interplay between SIRT1 and autophagy...
2017: PloS One
https://www.readbyqxmd.com/read/28817601/bortezomib-initiates-endoplasmic-reticulum-stress-elicits-autophagy-and-death-in-echinococcus-granulosus-larval-stage
#20
María Celeste Nicolao, Julia A Loos, Christian Rodriguez Rodrigues, Viviana Beas, Andrea C Cumino
Cystic echinococcosis (CE) is a worldwide distributed helminthic zoonosis caused by Echinococcus granulosus. Benzimidazole derivatives are currently the only drugs for chemotherapeutic treatment of CE. However, their low efficacy and the adverse effects encourage the search for new therapeutic targets. We evaluated the in vitro efficacy of Bortezomib (Bz), a proteasome inhibitor, in the larval stage of the parasite. After 96 h, Bz showed potent deleterious effects at a concentration of 5 μM and 0.5 μM in protoscoleces and metacestodes, respectively (P < 0...
2017: PloS One
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