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https://www.readbyqxmd.com/read/28334504/redd1-deficiency-impairs-autophagy-and-mitochondrial-biogenesis-in-articular-cartilage-and-increases-the-severity-of-experimental-osteoarthritis
#1
Oscar Alvarez-Garcia, Tokio Matsuzaki, Merissa Olmer, Lars Plate, Jeffery W Kelly, Martin K Lotz
Objective REDD1 is an endogenous inhibitor of mTOR that regulates cellular stress responses. REDD1 expression is decreased in aged and osteoarthritis (OA) cartilage and it regulates mTOR signaling and autophagy in articular chondrocytes in vitro. The present study investigated the effects of REDD1 deletion in vivo using a mouse model of experimental OA. Methods Severity of OA was histologically assessed in 4-month-old wild-type and in Redd1(-/-) mice subjected to surgical destabilization of the medial meniscus (DMM)...
March 23, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28296000/novel-application-of-localized-nanodelivery-of-anti-il6-protects-organ-transplant-from-ischemia-reperfusion-injuries
#2
Zhabiz Solhjou, Mayuko Uehara, Baharak Bahmani, Omar H Maarouf, Takaharu Ichimura, Craig R Brooks, Wanlong Xu, Mine Yilmaz, Abdala Elkhal, Stefan G Tullius, Indira Guleria, Martina McGrath, Reza Abdi
Ischemia reperfusion injury (IRI) evokes intra-graft inflammatory responses, which markedly augment alloimmune responses against the graft. Understanding the mechanisms underlying these responses is fundamental to develop therapeutic regimens to prevent/ameliorate organ IRI. Here, we demonstrate that IRI results in a marked increase in mitochondrial damage and autophagy in dendritic cells (DC). While autophagy is a survival mechanism for ischemic DC, it also augments their production of IL6. Allograft derived dendritic cells (ADDC) lacking autophagy related gene 5 (Atg5) showed higher death rates post-transplantation...
March 12, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28252104/altered-gene-expression-and-repressed-markers-of-autophagy-in-skeletal-muscle-of-insulin-resistant-patients-with-type-2-diabetes
#3
Andreas Buch Møller, Ulla Kampmann, Jakob Hedegaard, Kasper Thorsen, Iver Nordentoft, Mikkel Holm Vendelbo, Niels Møller, Niels Jessen
This case-control study was designed to investigate the gene expression profile in skeletal muscle from severely insulin resistant patients with long-standing type 2 diabetes (T2D), and to determine associated signaling pathways. Gene expression profiles were examined by whole transcriptome, strand-specific RNA-sequencing and associated signaling was determined by western blot. We identified 117 differentially expressed gene transcripts. Ingenuity Pathway Analysis related these differences to abnormal muscle morphology and mitochondrial dysfunction...
March 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28238968/changes-in-macroautophagy-chaperone-mediated-autophagy-and-mitochondrial-metabolism-in-murine-skeletal-and-cardiac-muscle-during-aging
#4
Jin Zhou, Shu Yun Chong, Andrea Lim, Brijesh K Singh, Rohit A Sinha, Adam B Salmon, Paul M Yen
Aging causes a general decline in cellular metabolic activity, and function in different tissues and whole body homeostasis. However, the understanding about the metabolomic and autophagy changes in skeletal muscle and heart during aging is still limited. We thus examined markers for macroautophagy, chaperone-mediated autophagy (CMA), mitochondrial quality control, as well as cellular metabolites in skeletal and cardiac muscle from young (5 months old) and aged (27 months old) mice. We found decreased autophagic degradation of p62 and increased ubiquitinated proteins in both tissues from aged mice, suggesting a decline in macroautophagy during aging...
February 26, 2017: Aging
https://www.readbyqxmd.com/read/28206988/inhibition-of-autophagy-blocks-cathepsins-tbid-mitochondrial-apoptotic-signaling-pathway-via-stabilization-of-lysosomal-membrane-in-ischemic-astrocytes
#5
Xian-Yong Zhou, Yu Luo, Yong-Ming Zhu, Zhi-He Liu, Thomas A Kent, Jia-Guo Rong, Wei Li, Shi-Gang Qiao, Min Li, Yong Ni, Kazumi Ishidoh, Hui-Ling Zhang
Our previous study and others have demonstrated that autophagy is activated in ischemic astrocytes and contributes to astrocytic cell death. However, the mechanisms of ischemia-induced autophagy remain largely unknown. In this study, we established a rat's model of permanent middle cerebral artery occlusion (pMCAO) and an in vitro oxygen and glucose deprivation (OGD) model. Autophagy was inhibited by either pharmacological treatment with 3-methyladenine (3-MA) and wortmannin (Wort) or genetic treatment with knockdown of Atg5 in primary cultured astrocytes and knockout of Atg5 in mouse embryonic fibroblast (MEF) cells, respectively...
February 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28163707/autophagy-is-impaired-in-neutrophils-from-streptozotocin-induced-diabetic-rats
#6
Wilson Mitsuo Tatagiba Kuwabara, Rui Curi, Tatiana Carolina Alba-Loureiro
We tested the hypothesis that changes reported on functions of neutrophils from streptozotocin-induced diabetic rats involve autophagy impairment. Wistar rats were rendered diabetic by streptozotocin injection (65 mg/kg, i.v.), and the measurements were carried out 2 weeks afterward. Neutrophils were collected through intraperitoneal cavity lavage after 4 h of i.p. oyster glycogen type 2 injection. Neutrophils cultured with PMA (20 nM) for 1 h were used for analysis of plasma membrane integrity, DNA fragmentation, and mitochondrial depolarization by flow cytometry; expression of Atg5, Atg14, Beclin1, LC3BII, and Rab9 by RT-PCR; the contents of caspase 3, LC3BII/LC3BI, and pS6 by western blotting; ATP content by fluorescence essay; reactive oxygen species production by chemiluminescence (Luminol), and autophagy by immunofluorescence tracking LC3B cleavage...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28131902/cq-synergistically-sensitizes-human-colorectal-cancer-cells-to-sn-38-cpt-11-through-lysosomal-and-mitochondrial-apoptotic-pathway-via-p53-ros-cross-talk
#7
Pinjia Chen, Xiaoyong Luo, Peipei Nie, Baoyan Wu, Wei Xu, Xinpeng Shi, Haocai Chang, Bing Li, Xiurong Yu, Zhengzhi Zou
Autophagy plays a key role in supporting cell survival against chemotherapy-induced apoptosis. In this study, we found the chemotherapy agent SN-38 induced autophagy in colorectal cancer (CRC) cells. However, inhibition of autophagy using a small molecular inhibitor 3-methyladenine (3-MA) and ATG5 siRNA did not increase SN-38-induced cytotoxicity in CRC cells. Notably, another autophagy inhibitor chloroquine (CQ) synergistically enhanced the anti-tumor activity of SN-38 in CRC cells with wild type (WT) p53...
March 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28106298/inhibition-of-inositol-1-4-5-trisphosphate-receptor-induce-breast-cancer-cell-death-through-deregulated-autophagy-and-cellular-bioenergetics
#8
Aru Singh, Megha Chagtoo, Swasti Tiwari, Nelson George, Bandana Chakravarti, Sajid Khan, Sripada Lakshmi, Madan M Godbole
Inositol 1,4,5-trisphosphate receptors (IP3 Rs) regulate autophagy in normal cells and are associated with metastasis in cancer cells. In breast cancer, however, the regulation and role of IP3 Rs is not clear. To study this we used MCF-7 breast cancer cell line and mouse model of breast cancer. Inhibiting IP3 R sub types resulted in compromised bioenergetics both in terms of glucose and mitochondrial metabolism. The siRNA mediated silencing of IP3 R or its blocking by its inhibitors Xestospongin C and 2-Amino-ethoxy diphenyl borate increased cell death and LC3II expression in MCF-7 cells as well as attenuated cellular bioenergetics...
January 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28103115/involvement-of-autophagy-in-nk-cell-development-and-function
#9
Alejandro López-Soto, José Manuel Bravo-San Pedro, Guido Kroemer, Lorenzo Galluzzi, Segundo Gonzalez
Natural killer (NK) cells are the prototypical members of the recently identified family of innate lymphoid cells (ILCs). Thanks to their cytotoxic and secretory functions, NK cells play a key role in the immune response to cells experiencing various forms of stress, including viral infection and malignant transformation. Autophagy is a highly conserved network of degradative pathways that participate in the maintenance of cellular and organismal homeostasis as they promote adaptation to adverse microenvironmental conditions...
March 4, 2017: Autophagy
https://www.readbyqxmd.com/read/28011320/autophagy-deficient-kupffer-cells-promote-tumorigenesis-by-enhancing-mtros-nf-%C3%AE%C2%BAb-il1%C3%AE-%C3%AE-dependent-inflammation-and-fibrosis-during-the-preneoplastic-stage-of-hepatocarcinogenesis
#10
Kai Sun, Lingyun Xu, Yingying Jing, Zhipeng Han, Xiaojing Chen, Chenlei Cai, Peipei Zhao, Xue Zhao, Liqun Yang, Lixin Wei
As a cellular degradation mechanism, autophagy exerts crucial and complicated effects on HCC development. Liver non-parenchymal cells, including hepatic resident macrophage Kupffer cells, also play important roles in this process. However, most associated studies have focused on the influence of the autophagy level in hepatic cells and HCC cells, but not liver non-parenchymal cells. Based on our previous study, we confirmed that Atg5 silence in the liver during the preneoplastic stage facilitated liver fibrosis, inflammation and, ultimately, tumorigenesis...
March 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27935055/subcellular-targeting-as-a-determinant-of-the-efficacy-of-photodynamic-therapy
#11
David Kessel
In prior studies, we have identified the ability of low-level lysosomal photodamage to potentiate the phototoxic effect of subsequent photodamage to mitochondria. The mechanism involves calpain-mediated cleavage of the autophagy-associated protein ATG5 to form a proapoptotic fragment (tATG5). In this report, we explore the permissible time lag between the two targeting procedures along with the effect of simultaneously targeting both lysosomes and mitochondria. This was found to be as effective as the sequential protocol with no gap between the irradiation steps...
March 2017: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/27911875/autophagy-flux-induced-by-ginsenoside-rg3-attenuates-human-prion-protein-mediated-neurotoxicity-and-mitochondrial-dysfunction
#12
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
#13
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
#14
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...
February 2017: Autophagy
https://www.readbyqxmd.com/read/27755961/marrubium-vulgare-ethanolic-extract-induces-proliferation-block-apoptosis-and-cytoprotective-autophagy-in-cancer-cells-in-vitro
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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