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Autophage and 继发性甲状旁腺功能亢进

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https://www.readbyqxmd.com/read/27936516/neuroprotection-of-hypoxic-postconditioning-against-global-cerebral-ischemia-through-influencing-posttranslational-regulations-of-heat-shock-protein-27-in-adult-rats
#1
Lixuan Zhan, Liu Liu, Kongping Li, Baoxing Wu, Dandan Liu, Donghai Liang, Haixia Wen, Yanmei Wang, Weiwen Sun, Weiping Liao, En Xu
We previously reported that hypoxic postconditioning (HPC) ameliorated hippocampal neuronal death induced by transient global cerebral ischemia (tGCI) in adult rats. However, the mechanism of HPC-induced neuroprotection is still elusive. Notably, heat shock protein 27 (Hsp27) has recently emerged as a potent neuroprotectant in cerebral ischemia. Although its robust protective effect on stroke has been recognized, the mechanism of Hsp27-mediated neuroprotection is largely unknown. Here, we investigated the potential molecular mechanism by which HPC modulates the posttranslational regulations of Hsp27 after tGCI...
December 9, 2016: Brain Pathology
https://www.readbyqxmd.com/read/27936094/lutein-attenuates-both-apoptosis-and-autophagy-upon-cobalt-ii-chloride-induced-hypoxia-in-rat-m%C3%A5-ller-cells
#2
Frederic K C Fung, Betty Y K Law, Amy C Y Lo
Retinal ischemia/reperfusion injury is a common feature of various retinal diseases such as glaucoma and diabetic retinopathy. Lutein, a potent anti-oxidant, is used to improve visual function in patients with age-related macular degeneration (AMD). Lutein attenuates apoptosis, oxidative stress and inflammation in animal models of acute retinal ischemia/hypoxia. Here, we further show that lutein improved Műller cell viability and enhanced cell survival upon hypoxia-induced cell death through regulation of intrinsic apoptotic pathway...
2016: PloS One
https://www.readbyqxmd.com/read/27935582/global-ischemia-induces-lysosomal-mediated-degradation-of-mtor-and-activation-of-autophagy-in-hippocampal-neurons-destined-to-die
#3
Jee-Yeon Hwang, Michael Gertner, Fabrizio Pontarelli, Brenda Court-Vazquez, Michael Vander Laan Bennett, Dimitry Ofengeim, Ruth Suzanne Zukin
The mammalian target of rapamycin (mTOR) is a key regulator of cell growth, autophagy, translation, and survival. Dysregulation of mTOR signaling is associated with cancer, diabetes, and autism. However, a role for mTOR signaling in neuronal death is not well delineated. Here we show that global ischemia triggers a transient increase in mTOR phosphorylation at S2448, whereas decreasing p-mTOR and functional activity in selectively vulnerable hippocampal CA1 neurons. The decrease in mTOR coincides with an increase in biochemical markers of autophagy, pS317-ULK-1, pS14-Beclin-1, and LC3-II, a decrease in the cargo adaptor p62, and an increase in autophagic flux, a functional readout of autophagy...
December 9, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27933980/nanoceria-mediated-drug-delivery-for-targeted-photodynamic-therapy-on-drug-resistant-breast-cancer
#4
Hong Li, Cong Liu, Yi-Ping Zeng, Yu-Hui Hao, Jia-Wei Huang, Zhang-You Yang, Rong Li
Photodynamic therapy (PDT) has shown great potential for overcoming drug-resistant cancers. Here, we report a multifunctional drug delivery system based on chlorin e6 (Ce6)/folic acid (FA)-loaded branched polyethylenimine-PEGylation ceria nanoparticles (PPCNPs-Ce6/FA), which was developed for targeted PDT to overcome drug-resistant breast cancers. Nanocarrier delivery and FA targeting significantly promoted the cellular uptake of photosensitizers (PSs), followed by their accumulation in lysosomes. PPCNPs-Ce6/FA generated reactive oxygen species (ROS) after near-infrared irradiation (NIR, 660 nm), leading to reduced P-glycoprotein (P-gp) expression, lysosomal membrane permeabilization (LMP), and excellent phototoxicity toward resistant MCF-7/ADR cells, even at ultralow doses...
November 23, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27933272/autophagy-dependent-secretion-contribution-to-tumor-progression
#5
REVIEW
Tom G Keulers, Marco B E Schaaf, Kasper M A Rouschop
Autophagy is best known as a lysosomal degradation and recycling pathway to maintain cellular homeostasis. During autophagy, cytoplasmic content is recognized and packed in autophagic vacuoles, or autophagosomes, and targeted for degradation. However, during the last years, it has become evident that the role of autophagy is not restricted to degradation alone but also mediates unconventional forms of secretion. Furthermore, cells with defects in autophagy apparently are able to reroute their cargo, like mitochondria, to the extracellular environment; effects that contribute to an array of pathologies...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27932981/proton-pump-inhibitors-display-antitumor-effects-in-barrett-s-adenocarcinoma-cells
#6
Eduardo Chueca, Nadezda Apostolova, Juan V Esplugues, María A García-González, Ángel Lanas, Elena Piazuelo
Recent evidence has reported that proton pump inhibitors (PPIs) can exert antineoplastic effects through the disruption of pH homeostasis by inhibiting vacuolar ATPase (H(+)-VATPase), a proton pump overexpressed in several tumor cells, but this aspect has not been deeply investigated in EAC yet. In the present study, the expression of H(+)-VATPase was assessed through the metaplasia-dysplasia-adenocarcinoma sequence in Barrett's esophagus (BE) and the antineoplastic effects of PPIs and cellular mechanisms involved were evaluated in vitro...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27932681/acute-intermittent-hypoxia-in-rats-activates-muscle-proteolytic-pathways-through-a-glucocorticoid-dependent-mechanism
#7
Franciele Przygodda, Leandro Henrique Manfredi, Juliano Machado, Dawit A P Gonçalves, Neusa Maria Zanon, Leni G H Bonagamba, Benedito H Machado, Isis do Carmo Kettelhut, Luiz C C Navegantes
Although it is well known that chronic hypoxia induces muscle wasting, the effects of intermit-tent hypoxia on skeletal muscle protein metabolism remains unclear. We hypothesized that acute intermittent hypoxia (AIH), a challenge that activates the hypothalamic-pituitary-adrenal axis, would alter muscle protein homeostasis through a glucocorticoid-dependent mechanism. Three-week-old rats were submitted to adrenalectomy (ADX) and exposed to 8 h of AIH (6% O2 for 40s at 9 min intervals). Animals were sacrificed and the soleus and extensor digitorum longus (EDL) muscles were harvested and incubated in vitro for measurements of protein turn-over...
December 8, 2016: Journal of Applied Physiology
https://www.readbyqxmd.com/read/27932527/mechanisms-of-in-vivo-ribosome-maintenance-change-in-response-to-nutrient-signals
#8
Andrew D Mathis, Bradley C Naylor, Richard H Carson, Eric Evans, Justin Harwell, Jared Knect, Eric Hexem, Fredrick Peelor, Benjamin F Miller, Karyn L Hamilton, Mark K Transtrum, Benjamin T Bikman, John C Price
Control of protein homeostasis is fundamental to the health and longevity of all organisms. Because the rate of protein synthesis by ribosomes is a central control point in this process, regulation and maintenance of ribosome function could have amplified importance in the overall regulatory circuit. Indeed, ribosomal defects are commonly associated with loss of protein homeostasis, aging and disease, whereas improved protein homeostasis, implying optimal ribosomal function, is associated with disease resistance and increased lifespan...
December 8, 2016: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/27932476/high-fat-diet-induced-lysosomal-dysfunction-and-impaired-autophagic-flux-contribute-to-lipotoxicity-in-the-kidney
#9
Takeshi Yamamoto, Yoshitsugu Takabatake, Atsushi Takahashi, Tomonori Kimura, Tomoko Namba, Jun Matsuda, Satoshi Minami, Jun-Ya Kaimori, Isao Matsui, Taiji Matsusaka, Fumio Niimura, Motoko Yanagita, Yoshitaka Isaka
Excessive fat intake contributes to the progression of metabolic diseases via cellular injury and inflammation, a process termed lipotoxicity. Here, we investigated the role of lysosomal dysfunction and impaired autophagic flux in the pathogenesis of lipotoxicity in the kidney. In mice, a high-fat diet (HFD) resulted in an accumulation of phospholipids in enlarged lysosomes within kidney proximal tubular cells (PTCs). In isolated PTCs treated with palmitic acid, autophagic degradation activity progressively stagnated in association with impaired lysosomal acidification and excessive lipid accumulation...
December 8, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27929731/autophagic-homeostasis-is-required-for-the-pluripotency-of-cancer-stem-cells
#10
Tanveer Sharif, Emma Martell, Cathleen Dai, Barry E Kennedy, Patrick Murphy, Derek Clements, Youra Kim, Patrick W K Lee, Shashi Gujar
Pluripotency is an important feature of cancer stem cells (CSCs) that contributes to self-renewal and chemoresistance. The maintenance of pluripotency of CSCs under various pathophysiological conditions requires a complex interaction between various cellular pathways including those involved in homeostasis and energy metabolism. However, the exact mechanisms that maintain the CSC pluripotency remain poorly understood. In this report, using both human and murine models of CSCs, we demonstrate that basal levels of autophagy are required to maintain the pluripotency of CSCs, and that this process is differentially regulated by the rate limiting enzyme in the NAD(+) synthesis pathway NAMPT (nicotinamide phosphoribosyltransferase) and the transcription factor POU5F1/OCT4 (POU class 5 homeobox 1)...
December 8, 2016: Autophagy
https://www.readbyqxmd.com/read/27929729/fyco1-and-autophagy-control-the-integrity-of-the-haploid-male-germ-cell-specific-rnp-granules
#11
Matteo Da Ros, Tiina Lehtiniemi, Opeyemi Olotu, Daniel Fischer, Fu-Ping Zhang, Helena Vihinen, Eija Jokitalo, Anu Sironen, Jorma Toppari, Noora Kotaja
Ribonucleoprotein (RNP) granules play a major role in compartmentalizing cytoplasmic RNA regulation. Haploid round spermatids that have exceptionally diverse transcriptomes are characterized by a unique germ cell-specific RNP granule, the chromatoid body (CB). The CB shares many characteristics with somatic RNP granules but also has germline-specific features. The CB appears to be a central structure in PIWI-interacting RNA (piRNA)-targeted RNA regulation. Here, we identified a novel CB component, FYCO1, which is involved in the intracellular transport of autophagic vesicles in somatic cells...
December 8, 2016: Autophagy
https://www.readbyqxmd.com/read/27929538/downregulation-of-aspp2-improves-hepatocellular-carcinoma-cells-survival-via-promoting-becn1-dependent-autophagy-initiation
#12
Rui Chen, Hao Wang, Beibei Liang, Guoke Liu, Min Tang, Rongjie Jia, Xiaoyu Fan, Wei Jing, Xuyu Zhou, Huajing Wang, Yang Yang, Huafeng Wei, Bohua Li, Jian Zhao
Autophagy is an important catabolic process, which sustains intracellular homeostasis and lengthens cell survival under stress. Here we identify the ankyrin-repeat-containing, SH3-domain-containing, and proline-rich region-containing protein 2 (ASPP2), a haploinsufficient tumor suppressor, as a molecular regulator of starvation-induced autophagy in hepatocellular carcinoma (HCC). ASPP2 expression is associated with an autophagic response upon nutrient deprivation and downregulation of ASPP2 facilitates autophagic flux, whereas overexpression of ASPP2 blocks this starvation-induced autophagy in HCC cells...
December 8, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27929536/hyperhomocysteinemia-causes-er-stress-and-impaired-autophagy-that-is-reversed-by-vitamin-b-supplementation
#13
Madhulika Tripathi, Cheng Wu Zhang, Brijesh Kumar Singh, Rohit Anthony Sinha, Kyaw Thu Moe, Deidre Anne DeSilva, Paul Michael Yen
Hyperhomocysteinemia (HHcy) is a well-known risk factor for stroke; however, its underlying molecular mechanism remains unclear. Using both mouse and cell culture models, we have provided evidence that impairment of autophagy has a central role in HHcy-induced cellular injury in the mouse brain. We observed accumulation of LC3B-II and p62 that was associated with increased MTOR signaling in human and mouse primary astrocyte cell cultures as well as a diet-induced mouse model of HHcy, HHcy decreased lysosomal membrane protein LAMP2, vacuolar ATPase (ATP6V0A2), and protease cathepsin D, suggesting that lysosomal dysfunction also contributed to the autophagic defect...
December 8, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27929117/cct-complex-restricts-neuropathogenic-protein-aggregation-via-autophagy
#14
Mariana Pavel, Sara Imarisio, Fiona M Menzies, Maria Jimenez-Sanchez, Farah H Siddiqi, Xiaoting Wu, Maurizio Renna, Cahir J O'Kane, Damian C Crowther, David C Rubinsztein
Aberrant protein aggregation is controlled by various chaperones, including CCT (chaperonin containing TCP-1)/TCP-1/TRiC. Mutated CCT4/5 subunits cause sensory neuropathy and CCT5 expression is decreased in Alzheimer's disease. Here, we show that CCT integrity is essential for autophagosome degradation in cells or Drosophila and this phenomenon is orchestrated by the actin cytoskeleton. When autophagic flux is reduced by compromise of individual CCT subunits, various disease-relevant autophagy substrates accumulate and aggregate...
December 8, 2016: Nature Communications
https://www.readbyqxmd.com/read/27928645/braf-v600e-dependent-role-of-autophagy-in-uveal-melanoma
#15
Yinu Zhao, Weibin Wang, Irene Min, Brian Wyrwas, Maureen Moore, Rasa Zarnegar, Thomas J Fahey
BACKGROUND: Autophagy can function in a dual role in cancer development and progression: It can be cytoprotective or contribute to cell death. Therefore, determining the contextual role of autophagy between these two opposing effects is important. So far, little is known about the role of autophagy in uveal melanoma. In the present study, we looked to investigate the autophagic process, as well as its effect on cell survival in uveal melanoma cell lines under stressed conditions (starvation)...
December 7, 2016: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/27928028/mitochondrial-pyruvate-carrier-regulates-autophagy-inflammation-and-neurodegeneration-in-experimental-models-of-parkinson-s-disease
#16
Anamitra Ghosh, Trevor Tyson, Sonia George, Erin N Hildebrandt, Jennifer A Steiner, Zachary Madaj, Emily Schulz, Emily Machiela, William G McDonald, Martha L Escobar Galvis, Jeffrey H Kordower, Jeremy M Van Raamsdonk, Jerry R Colca, Patrik Brundin
Mitochondrial and autophagic dysfunction as well as neuroinflammation are involved in the pathophysiology of Parkinson's disease (PD). We hypothesized that targeting the mitochondrial pyruvate carrier (MPC), a key controller of cellular metabolism that influences mTOR (mammalian target of rapamycin) activation, might attenuate neurodegeneration of nigral dopaminergic neurons in animal models of PD. To test this, we used MSDC-0160, a compound that specifically targets MPC, to reduce its activity. MSDC-0160 protected against 1-methyl-4-phenylpyridinium (MPP(+)) insult in murine and cultured human midbrain dopamine neurons and in an α-synuclein-based Caenorhabditis elegans model...
December 7, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27927774/autophagy-inhibition-enhances-sunitinib-efficacy-in-clear-cell-ovarian-carcinoma
#17
Lindsay DeVorkin, Matthew Hattersley, Paul Kim, Jenna Ries, Jaeline Spowart, Michael S Anglesio, Samuel M Levi, David G Huntsman, Ravi K Amaravadi, Jeffrey D Winkler, Anna V Tinker, Julian J Lum
: Clear cell ovarian carcinoma (CCOC) is an aggressive form of epithelial ovarian cancer that exhibits low response rates to systemic therapy and poor patient outcomes. Multiple studies in CCOC have revealed expression profiles consistent with increased hypoxia, and our previous data suggests that hypoxia is correlated with increased autophagy in CCOC. Hypoxia-induced autophagy is a key factor promoting tumor cell survival and resistance to therapy. Recent clinical trials with the molecular-targeted receptor tyrosine kinase (RTK) inhibitor sunitinib have demonstrated limited activity...
December 7, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27927596/quantification-of-muscle-pathology-in-infantile-pompe-disease
#18
Anne Schänzer, Ann-Kathrin Kaiser, Christian Mühlfeld, Martin Kulessa, Werner Paulus, Harald von Plein, Marianne Rohrbach, Lara Viergutz, Eugen Mengel, Thorsten Marquardt, Bern Neubauer, Till Acker, Andreas Hahn
The effects of enzyme replacement therapy (ERT) in infantile Pompe disease are variable, necessitating the identification of biomarkers to assess the severity of disease and response to ERT. The aims of this study were to investigate whether quantification of muscle pathology in infantile Pompe disease prior to and during ERT is feasible at the light microscope, and to develop a score that summarizes the degree of muscle pathology in a comprehensive manner from PAS-stained resin sections alone. We, therefore, determined glycogen load, extent of muscle fibre disruption, and amount of autophagic vacuoles in resin-embedded muscle biopsy specimens from 11 infantile Pompe patients and 2 with early childhood phenotype by quantitative methods, correlated the findings with ultrastructural analyses, compared PAS-stained resin sections with conventional PAS-stained cryosections, and related the quantified degree of muscle damage from infantile patients to the effects of ERT...
November 3, 2016: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/27927076/evidence-of-biological-activity-of-mentha-species-extracts-on-apoptotic-and-autophagic-targets-on-murine-raw264-7-and-human-u937-monocytic-cells
#19
Fatiha Brahmi, Samia Hadj-Ahmed, Amira Zarrouk, Maryem Bezine, Thomas Nury, Khodir Madani, Mohamed Chibane, Anne Vejux, Pierre Andreoletti, Lila Boulekbache-Makhlouf, Gérard Lizard
CONTEXT: Mints (Lamiaceae) are used as traditional remedies for the treatment of several diseases. Their extracts are recognized as anti-inflammatory compounds. OBJECTIVE: This study characterized the cytotoxic effects of Mentha spicata L. (MS), Mentha pulegium L. (MP) and Mentha rotundifolia (L). Huds (MR) on macrophage cells (RAW264.7; U937) and determined their impact on apoptosis and autophagy, which can play a role in controlling inflammation. MATERIALS AND METHODS: The extracts were prepared in culture medium and tested from 25 to 400 μg/mL after 24-48 h of treatment...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/27925395/persistency-of-enlarged-autolysosomes-underscores-nanoparticle-induced-autophagy-in-hepatocytes
#20
Ji-Qian Zhang, Wei Zhou, Sha-Sha Zhu, Jun Lin, Peng-Fei Wei, Fen-Fen Li, Pei-Pei Jin, Han Yao, Yun-Jiao Zhang, Yi Hu, Yi-Ming Liu, Ming Chen, Zheng-Quan Li, Xue-Sheng Liu, Li Bai, Long-Ping Wen
The diverse biological effects of nanomaterials form the basis for their applications in biomedicine but also cause safety issues. Induction of autophagy is a cellular response after nanoparticles exposure. It may be beneficial in some circumstances, yet autophagy-mediated toxicity raises an alarming concern. Previously, it has been reported that upconversion nanoparticles (UCNs) elicit liver damage, with autophagy contributing most of this toxicity. However, the detailed mechanism is unclear. This study reveals persistent presence of enlarged autolysosomes in hepatocytes after exposure to UCNs and SiO2 nanoparticles both in vitro and in vivo...
December 7, 2016: Small
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