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https://www.readbyqxmd.com/read/27911875/autophagy-flux-induced-by-ginsenoside-rg3-attenuates-human-prion-protein-mediated-neurotoxicity-and-mitochondrial-dysfunction
#1
Ji-Hong Moon, Ju-Hee Lee, You-Jin Lee, Sang-Youel Park
Mitochondrial quality control is a process by which mitochondria undergo successive rounds of fusion and fission with dynamic exchange of components to segregate functional and damaged elements. Removal of mitochondrion that contains damaged components is accomplished via autophagy. In this study, we investigated whether ginsenoside Rg3, an active ingredient of the herbal medicine ginseng that is used as a tonic and restorative agent, could attenuate prion peptide, PrP (106-126)-induced neurotoxicity and mitochondrial damage...
November 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27896021/lithocholic-acid-induces-endoplasmic-reticulum-stress-autophagy-and-mitochondrial-dysfunction-in-human-prostate-cancer-cells
#2
Ahmed A Gafar, Hossam M Draz, Alexander A Goldberg, Mohamed A Bashandy, Sayed Bakry, Mahmoud A Khalifa, Walid AbuShair, Vladimir I Titorenko, J Thomas Sanderson
Lithocholic acid (LCA) is a secondary bile acid that is selectively toxic to human neuroblastoma, breast and prostate cancer cells, whilst sparing normal cells. We previously reported that LCA inhibited cell viability and proliferation and induced apoptosis and necrosis of androgen-dependent LNCaP and androgen-independent PC-3 human prostate cancer cells. In the present study, we investigated the roles of endoplasmic reticulum (ER) stress, autophagy and mitochondrial dysfunction in the toxicity of LCA in PC-3 and autophagy deficient, androgen-independent DU-145 cells...
2016: PeerJ
https://www.readbyqxmd.com/read/27875077/march5-rna-promotes-autophagy-migration-and-invasion-of-ovarian-cancer-cells
#3
Jianguo Hu, Ying Meng, Zhanqin Zhang, Qiuting Yan, Xingwei Jiang, Zilan Lv, Lina Hu
MARCH5 is a crucial regulator of mitochondrial fission. However, the expression and function of MARCH5 in ovarian cancer have not been determined. This study investigated the expression and function of MARCH5 in ovarian cancer with respect to its potential role in the tumorigenesis of the disease as well as its usefulness as an early diagnostic marker. We found that the expression of MARCH5 was substantially upregulated in ovarian cancer tissue in comparison with the normal control. Silencing MARCH5 in SKOV3 cells decreased TGFB1-induced cell macroautophagy/autophagy, migration, and invasion in vitro and in vivo, whereas the ectopic expression of MARCH5 in A2780 cells had the opposite effect...
November 22, 2016: Autophagy
https://www.readbyqxmd.com/read/27755961/marrubium-vulgare-ethanolic-extract-induces-proliferation-block-apoptosis-and-cytoprotective-autophagy-in-cancer-cells-in-vitro
#4
V Paunovic, M Kosic, S Djordjevic, A Zugic, N Djalinac, U Gasic, V Trajkovic, J Harhaji-Trajkovic
Marrubium vulgare is a European medicinal plant with numerous beneficial effects on human health. The aim of the study was to isolate the plant ethanolic extract (MVE) and to investigate its anti-melanoma and anti-glioma effects. MVE was prepared by the modified pharmacopoeial percolation method and characterized by UHPLC-LTQ OrbiTrap MS. MVE dose-dependently reduced viability of melanoma (B16) and glioma (U251) cells, but not peripheral blood mononuclear cells. It arrested cell cycle in S+G2/M phase, which was associated with the activation of MAP kinase p38 and up-regulation of antiproliferative genes p53, p21 and p27...
September 30, 2016: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/27633131/autophagy-related-proteins-are-functionally-active-in-human-spermatozoa-and-may-be-involved-in-the-regulation-of-cell-survival-and-motility
#5
I M Aparicio, J Espino, I Bejarano, A Gallardo-Soler, M L Campo, G M Salido, J A Pariente, F J Peña, J A Tapia
Macroautophagy (hereafter autophagy) is an evolutionarily highly conserved cellular process that participates in the maintenance of intracellular homeostasis through the degradation of most long-lived proteins and entire organelles. Autophagy participates in some reproductive events; however, there are not reports regarding the role of autophagy in the regulation of sperm physiology. Hence, the aim of this study was to investigate whether autophagy-related proteins are present and functionally active in human spermatozoa...
September 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27568548/beige-adipocyte-maintenance-is-regulated-by-autophagy-induced-mitochondrial-clearance
#6
Svetlana Altshuler-Keylin, Kosaku Shinoda, Yutaka Hasegawa, Kenji Ikeda, Haemin Hong, Qianqian Kang, Yangyu Yang, Rushika M Perera, Jayanta Debnath, Shingo Kajimura
Beige adipocytes gained much attention as an alternative cellular target in anti-obesity therapy. While recent studies have identified a number of regulatory circuits that promote beige adipocyte differentiation, the molecular basis of beige adipocyte maintenance remains unknown. Here, we demonstrate that beige adipocytes progressively lose their morphological and molecular characteristics after withdrawing external stimuli and directly acquire white-like characteristics bypassing an intermediate precursor stage...
September 13, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27528614/differences-and-similarities-in-trail-and-tumor-necrosis-factor-mediated-necroptotic-signaling-in-cancer-cells
#7
Justyna Sosna, Stephan Philipp, Johaiber Fuchslocher Chico, Carina Saggau, Jürgen Fritsch, Alexandra Föll, Johannes Plenge, Christoph Arenz, Thomas Pinkert, Holger Kalthoff, Anna Trauzold, Ingo Schmitz, Stefan Schütze, Dieter Adam
Recently, a type of regulated necrosis (RN) called necroptosis was identified to be involved in many pathophysiological processes and emerged as an alternative method to eliminate cancer cells. However, only a few studies have elucidated components of TRAIL-mediated necroptosis useful for anticancer therapy. Therefore, we have compared this type of cell death to tumor necrosis factor (TNF)-mediated necroptosis and found similar signaling through acid and neutral sphingomyelinases, the mitochondrial serine protease HtrA2/Omi, Atg5, and vacuolar H(+)-ATPase...
October 15, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27508931/overexpression-of-hypo-phosphorylated-i%C3%AE%C2%BAb%C3%AE-at-ser313-protects-the-heart-against-sepsis
#8
Guang-Qing Wang, Tao Tang, Zhong-Shan Wang, Ying-Ying Liu, Li Wang, Peng-Fei Luo, Zhao-Fan Xia
IκBβis an inhibitor of nuclear factor kappa B(NF-κB) and participates in the cardiac response to sepsis. However, the role of the hypo-phosphorylated form of IκBβ at Ser313, which can be detected during sepsis, is unknown. Here, we examined the effects of IκBβ with a mutation at Ser313→Ala313 on cardiac damage induced by sepsis. Transgenic (Tg) mice were generated to overexpress IκBβ, in which Ser-313 is replaced with alanine ubiquitously, in order to mimic the hypo-phosphorylated form of IκBβ...
2016: PloS One
https://www.readbyqxmd.com/read/27507051/bh3-mimetic-obatoclax-gx15-070-mediates-mitochondrial-stress-predominantly-via-mcl-1-inhibition-and-induces-autophagy-dependent-necroptosis-in-human-oral-cancer-cells
#9
Prasad Sulkshane, Tanuja Teni
We have previously reported overexpression of antiapoptotic MCL-1 protein in human oral cancers and its association with therapy resistance and poor prognosis, implying it to be a potential therapeutic target. Hence, we investigated the efficacy and mechanism of action of Obatoclax, a BH3 mimetic pan BCL-2 inhibitor in human oral cancer cell lines. All cell lines exhibited high sensitivity to Obatoclax with complete clonogenic inhibition at 200-400 nM concentration which correlated with their MCL-1 expression...
August 5, 2016: Oncotarget
https://www.readbyqxmd.com/read/27428704/new-insights-into-the-pathways-initiating-and-driving-pancreatitis
#10
Anna S Gukovskaya, Stephen J Pandol, Ilya Gukovsky
PURPOSE OF REVIEW: In this article, we discuss recent studies that advance our understanding of molecular and cellular factors initiating and driving pancreatitis, with the emphasis on the role of acinar cell organelle disorders. RECENT FINDINGS: The central physiologic function of the pancreatic acinar cell - to synthesize, store, and secrete digestive enzymes - critically relies on coordinated actions of the endoplasmic reticulum (ER), the endolysosomal system, mitochondria, and autophagy...
July 13, 2016: Current Opinion in Gastroenterology
https://www.readbyqxmd.com/read/27413105/perfluorooctane-sulfonate-induces-autophagy-dependent-apoptosis-through-spinster-1-mediated-lysosomal-mitochondrial-axis-and-impaired-mitophagy
#11
Xiaofeng Yao, Shanshan Sha, Yuexia Wang, Xiance Sun, Jun Cao, Jian Kang, Liping Jiang, Min Chen, Yufang Ma
Lysosomal membrane permeabilization (LMP) and subsequently impaired autophagosome degradation was induced in HepG2 cells after treatment with perfluorooctane sulfonate (PFOS) for 24 h in our previous studies. We found that treatment of HepG2 cells with PFOS-induced autophagosome formation at earlier stage (6 h) of treatment in this study. The autophagosome formation inhibitor 3-methyladenine (3-MA) was able to relieve PFOS-induced LMP and release of cathepsin D in HepG2 cells. Knockdown of Spinster 1, a lysosomal membrane permease, attenuated PFOS-induced LMP in HepG2 cells...
September 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/27412471/the-nephroprotection-exerted-by-curcumin-in-maleate-induced-renal-damage-is-associated-with-decreased-mitochondrial-fission-and-autophagy
#12
Eduardo Molina-Jijón, Omar Emiliano Aparicio-Trejo, Rafael Rodríguez-Muñoz, Juan Carlos León-Contreras, María Del Carmen Cárdenas-Aguayo, Omar Noel Medina-Campos, Edilia Tapia, Laura Gabriela Sánchez-Lozada, Rogelio Hernández-Pando, José L Reyes, Laura Arreola-Mendoza, José Pedraza-Chaverri
We have previously reported that the antioxidant curcumin exerts nephroprotection in maleate-induced renal damage, a model associated with oxidative stress. However, the mechanisms involved in curcumin protective effect were not explored, to assess this issue, curcumin was administered daily by gavage (150 mg/kg) five days before a single maleate (400 mg/kg)-injection. Curcumin prevented maleate-induced proteinuria, increased heat shock protein of 72 KDa (Hsp72) expression, and decreased plasma glutathione peroxidase activity...
July 13, 2016: BioFactors
https://www.readbyqxmd.com/read/27366944/basal-autophagy-is-pivotal-for-hodgkin-and-reed-sternberg-cells-survival-and-growth-revealing-a-new-strategy-for-hodgkin-lymphoma-treatment
#13
Katrin Birkenmeier, Katharina Moll, Sebastian Newrzela, Sylvia Hartmann, Stefan Dröse, Martin-Leo Hansmann
As current classical Hodgkin lymphoma (cHL) treatment strategies have pronounced side-effects, specific inhibition of signaling pathways may offer novel strategies in cHL therapy. Basal autophagy, a regulated catabolic pathway to degrade cell's own components, is in cancer linked with both, tumor suppression or promotion. The finding that basal autophagy enhances tumor cell survival would thus lead to immediately testable strategies for novel therapies. Thus, we studied its contribution in cHL.We found constitutive activation of autophagy in cHL cell lines and primary tissue...
June 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27334109/the-pink1-synphilin-1-and-siah-1-complex-constitutes-a-novel-mitophagy-pathway
#14
Raymonde Szargel, Vered Shani, Fatimah Abd Elghani, Lucy N Mekies, Esti Liani, Ruth Rott, Simone Engelender
PTEN-induced putative kinase 1 (PINK1) and parkin are mutated in familial forms of Parkinson's disease and are important in promoting the mitophagy of damaged mitochondria. In this study, we showed that synphilin-1 interacted with PINK1 and was recruited to the mitochondria. Once in the mitochondria, it promoted PINK1-dependent mitophagy, as revealed by Atg5 knockdown experiments and the recruitment of LC3 and Lamp1 to the mitochondria. PINK1-synphilin-1 mitophagy did not depend on PINK1-mediated phosphorylation of synphilin-1 and occurred in the absence of parkin...
June 22, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27182794/abrus-agglutinin-a-type-ii-ribosome-inactivating-protein-inhibits-akt-ph-domain-to-induce-endoplasmic-reticulum-stress-mediated-autophagy-dependent-cell-death
#15
Prashanta Kumar Panda, Birendra Behera, Biswa Ranjan Meher, Durgesh Nandini Das, Subhadip Mukhopadhyay, Niharika Sinha, Prajna Paramita Naik, Bibhas Roy, Joyjyoti Das, Subhankar Paul, Tapas K Maiti, Rajesh Agarwal, Sujit K Bhutia
Abrus agglutinin (AGG), a type II ribosome-inactivating protein has been found to induce mitochondrial apoptosis. In the present study, we documented that AGG-mediated Akt dephosphorylation led to ER stress resulting the induction of autophagy-dependent cell death through the canonical pathway in cervical cancer cells. Inhibition of autophagic death with 3-methyladenosine (3-MA) and siRNA of Beclin-1 and ATG5 increased AGG-induced apoptosis. Further, inhibiting apoptosis by Z-DEVD-FMK and N-acetyl cysteine (NAC) increased autophagic cell death after AGG treatment, suggesting that AGG simultaneously induced autophagic and apoptotic death in HeLa cells...
May 16, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27163877/loss-of-autophagy-enhances-mif-macrophage-migration-inhibitory-factor-release-by-macrophages
#16
Jacinta P W Lee, Andrew Foote, Huapeng Fan, Celia Peral de Castro, Tali Lang, Sarah A Jones, Nichita Gavrilescu, Kingston H G Mills, Michelle Leech, Eric F Morand, James Harris
MIF (macrophage migration inhibitory factor [glycosylation-inhibiting factor]) is a pro-inflammatory cytokine expressed in multiple cells types, including macrophages. MIF plays a pathogenic role in a number of inflammatory diseases and has been linked to tumor progression in some cancers. Previous work has demonstrated that loss of autophagy in macrophages enhances secretion of IL1 family cytokines. Here, we demonstrate that loss of autophagy, by pharmacological inhibition or siRNA silencing of Atg5, enhances MIF secretion by monocytes and macrophages...
June 2, 2016: Autophagy
https://www.readbyqxmd.com/read/27099069/parthenolide-induces-apoptosis-and-autophagy-through-the-suppression-of-pi3k-akt-signaling-pathway-in-cervical-cancer
#17
Sridharan Jeyamohan, Rajesh Kannan Moorthy, Mahesh Kumar Kannan, Antony Joseph Velanganni Arockiam
OBJECTIVE: To investigate the effect of parthenolide on apoptosis and autophagy and to study the role of the PI3K/Akt signaling pathway in cervical cancer. RESULTS: Parthenolide inhibits HeLa cell viability in a dose dependent-manner and was confirmed by MTT assay. Parthenolide (6 µM) induces mitochondrial-mediated apoptosis and autophagy by activation of caspase-3, upregulation of Bax, Beclin-1, ATG5, ATG3 and down-regulation of Bcl-2 and mTOR. Parthenolide also inhibits PI3K and Akt expression through activation of PTEN expression...
August 2016: Biotechnology Letters
https://www.readbyqxmd.com/read/27096545/promotion-of-proapoptotic-signals-by-lysosomal-photodamage-mechanistic-aspects-and-influence-of-autophagy
#18
David Kessel, Conor L Evans
Prior studies demonstrated that a low level (LD10-15 ) of lysosomal photodamage can sensitize cells to the apoptotic death that results from subsequent mitochondrial photodamage. We have proposed that this process occurs via a calpain-catalyzed cleavage of the autophagy-associated protein ATG5 to form a proapoptotic fragment. In this report, we provide evidence for the postulated ATG5 cleavage and show that the sequential photodynamic therapy (PDT) protocol can also partly overcome the adverse effect of hypoxia on the initiation of apoptosis...
July 2016: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/27082295/prolyl-4-hydroxylases-inhibitor-stabilizes-hif-1%C3%AE-and-increases-mitophagy-to-reduce-cell-death-after-experimental-retinal-detachment
#19
Haiyang Liu, Hong Zhu, Tong Li, Pengfei Zhang, Ning Wang, Xiaodong Sun
PURPOSE: This study investigated the neuroprotective effect against photoreceptor cell death using prolyl-4-hydroxylases inhibitor (PHI), an HIF-1α stabilizer, in experimental retinal detachment (RD). METHODS: RD was created in Brown Norway rats by subretinal injection of 1% sodium hyaluronate. FG-4592 (a PHI, 25 mg/kg) or a vehicle was administered every 2 days with retro-orbital injection. Photoreceptor death was evaluated by TdT-dUTP terminal nick-end labeling (TUNEL) assay 3 days after RD and by the thickness of the outer nuclear layer 7 days after RD...
April 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27058536/autophagic-cell-death-and-apoptosis-jointly-mediate-cisatracurium-besylate-induced-cell-injury
#20
Haixia Zhuang, Weili Tian, Wen Li, Xingli Zhang, Jingjing Wang, Yue Yang, Xin Liu, Zhengyuan Xia, Du Feng, Liangqing Zhang
Cisatracurium besylate is an ideal non-depolarizing muscle relaxant which is widely used in clinical application. However, some studies have suggested that cisatracurium besylate can affect cell proliferation. Moreover, its specific mechanism of action remains unclear. Here, we found that the number of GFP-LC3 (green fluoresent protein-light chain 3) positive autophagosomes and the rate of mitochondria fracture both increased significantly in drug-treated GFP-LC3 and MitoDsRed stable HeLa cells. Moreover, cisatracurium promoted the co-localization of LC3 and mitochondria and induced formation of autolysosomes...
2016: International Journal of Molecular Sciences
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