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https://www.readbyqxmd.com/read/28813698/caspase-independent-pathway-is-related-to-nilotinib-cytotoxicity-in-cultured-cardiomyocytes
#1
Qinghui Yang, Chunhui Zhang, Hong Wei, Zenghui Meng, Guangnan Li, Yuanyuan Xu, Yanjun Chen
BACKGROUND/AIMS: Cardiotoxicity is a predominant side-effect of nilotinib during chronic myeloid leukemia treatment. The underlying molecular mechanism remains unclear. The role of autophagy and mitochondrial signaling was investigated in nilotinib-treated cardiac H9C2 cells. METHODS: Cytotoxicity was assessed using Cell Death Detection kit. Immunoblot and immunofluorescence staining was performed, and cathepsin B and caspase3 activity was assessed in nilotinib-treated H9C2 cells with or without distinct pathway inhibitor or specific siRNA...
August 15, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28801211/parkin-clearance-of-dysfunctional-mitochondria-regulates-ros-levels-and-increases-survival-of-human-chondrocytes
#2
M Y Ansari, N M Khan, I Ahmad, T M Haqqi
OBJECTIVE: Mitochondrial dysfunction, oxidative stress and chondrocyte death are important contributors to the development and pathogenesis of osteoarthritis (OA). In this study, we determined the expression and role of Parkin in the clearance of damaged/dysfunctional mitochondria, regulation of reactive oxygen species (ROS) levels and chondrocyte survival under pathological conditions. METHODS: Human chondrocytes were from the unaffected area of knee OA cartilage (n = 12) and were stimulated with IL-1β to mimic pathological conditions...
August 8, 2017: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/28774732/downregulation-of-tigar-sensitizes-the-antitumor-effect-of-physapubenolide-through-increasing-intracellular-ros-levels-to-trigger-apoptosis-and-autophagosome-formation-in-human-breast-carcinoma-cells
#3
Ting Ma, Yi Zhang, Chao Zhang, Jian-Guang Luo, Ling-Yi Kong
Physapubenolide (PB) is a cytotoxic withanolide isolated from Physalis angulate that was used as a traditional Chinese medicine. In this study, we investigated the role of TIGAR and ROS in PB-induced apoptosis and autophagosome formation in human breast carcinoma MDA-MB-231 and MCF-7 cells. PB induced apoptosis by decreasing mitochondrial membrane potential and elevating the Bax/Bcl-2 protein expression ratio in MDA-MB-231 and MCF-7 cells. Caspase inhibitor Z-VAD-FMK treatment partly blocked PB induced cytotoxicity, suggesting that apoptosis serves as an important role in the anti-proliferative effect of PB...
July 31, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28729463/dietary-pufas-attenuate-nlrp3-inflammasome-activation-via-enhancing-macrophage-autophagy
#4
Lulu Shen, Yan Yang, Tiantong Ou, Chia-Chi C Key, Sarah H Tong, Russel C Sequeira, Jonathan M Nelson, Yan Nie, Zhan Wang, Elena Boudyguina, Swapnil V Shewale, Xuewei Zhu
Dietary PUFAs reduce atherosclerosis and macrophage inflammation, but how NLRP3 inflammasome activation and autophagy influence PUFA-mediated atheroprotection is poorly understood. We fed Ldlr-/- mice diets containing 10% (calories) palm oil (PO) and 0.2% cholesterol, supplemented with an additional 10% of calories as PO, fish oil (FO), echium oil (EO, containing 18:4 n-3), or borage oil (BO, containing 18:3 n-6). Inflammasome activation, autophagic flux, and mitochondrial function were measured in peritoneal macrophages, blood monocytes, or liver from diet-fed mice...
July 20, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28696570/effects-of-combined-lysosomal-and-mitochondrial-photodamage-in-a-non-small-cell-lung-cancer-cell-line-the-role-of-paraptosis
#5
David Kessel, John J Reiners
We previously reported that a low-level of lysosomal photodamage potentiated the phototoxic effect of subsequent mitochondrial photodamage mediated by the benzoporphyrin derivative BPD in murine hepatoma 1c1c7 cells. This was attributed to release of Ca(2+) from damaged lysosomes and a calpain-mediated conversion of the autophagy-related protein ATG5 to a pro-apoptotic fragment. We now report a comparison of these results with those obtained with the human non small-cell lung cancer A549 cell line. A549 cells contained lower levels of ATG5 and were less responsive than 1c1c7 cultures to the PDT combination...
July 11, 2017: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/28679997/alternative-autophagy-plays-a-central-role-in-mitochondria-elimination-from-reticulocytes
#6
Shigeomi Shimizu
Mitophagy is a mitochondrial quality control mechanism where damaged and surplus mitochondria are degraded by macroautophagy. Mitophagy is associated with various physiological and pathological events such as mitochondrial clearance during the terminal differentiation of reticulocytes. There are two different mammalian autophagy pathways: the Atg5-dependent conventional pathway and Atg5-independent alternative pathway; the latter is involved in reticulocyte's mitophagy.
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28671312/anti-prostate-cancer-potential-of-gossypetin-via-inducing-apoptotic-and-autophagic-cell-death
#7
Ming-Shih Lee, Chia-Wen Tsai, Chi-Ping Wang, Jing-Hsien Chen, Hui-Hsuan Lin
Gossypetin (GTIN), a naturally occurring hexahydroxy flavone, has been shown to possess antimutagenic, antioxidant, antimicrobial, and antiatherosclerotic effects. Here, we investigated the mechanism(s) underlying the anticancer potential of GTIN. In this study, investigations were showed that GTIN preferentially induces programed cell death of prostate cancer (PCa) cells in vitro and in vivo. MTT data showed that GTIN exhibited the anti-proliferation effect on human PCa cells in a dose- and time-dependent manner...
July 3, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28647341/suppression-of-autophagic-flux-contributes-to-cardiomyocyte-death-by-activation-of-necroptotic-pathways
#8
Makoto Ogasawara, Toshiyuki Yano, Masaya Tanno, Koki Abe, Satoko Ishikawa, Takayuki Miki, Atsushi Kuno, Toshiyuki Tobisawa, Shingo Muratsubaki, Kouhei Ohno, Yuki Tatekoshi, Kei Nakata, Wataru Ohwada, Tetsuji Miura
BACKGROUND: The role of necroptosis in myocardial injury has not been fully characterized. Here we examined roles of mitochondrial permeability transition pore (mPTP) and autophagy in necroptosis of cardiomyocytes. METHODS AND RESULTS: In H9c2 cells, necroptosis was induced by treatment with TNF-α (TNF) and z-VAD-fmk (zVAD) for 24h, and necroptotic death was determined by LDH release (as % of total). TNF/zVAD increased LDH release from 16.6±4.3% to 60.6±2.7%, and the LDH release was suppressed by necrostatin-1 (29...
June 21, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28577568/pirfenidone-inhibits-myofibroblast-differentiation-and-lung-fibrosis-development-during-insufficient-mitophagy
#9
Yusuke Kurita, Jun Araya, Shunsuke Minagawa, Hiromichi Hara, Akihiro Ichikawa, Nayuta Saito, Tsukasa Kadota, Kazuya Tsubouchi, Nahoko Sato, Masahiro Yoshida, Kenji Kobayashi, Saburo Ito, Yu Fujita, Hirofumi Utsumi, Haruhiko Yanagisawa, Mitsuo Hashimoto, Hiroshi Wakui, Yutaka Yoshii, Takeo Ishikawa, Takanori Numata, Yumi Kaneko, Hisatoshi Asano, Makoto Yamashita, Makoto Odaka, Toshiaki Morikawa, Katsutoshi Nakayama, Kazuyoshi Kuwano
BACKGROUND: Pirfenidone (PFD) is an anti-fibrotic agent used to treat idiopathic pulmonary fibrosis (IPF), but its precise mechanism of action remains elusive. Accumulation of profibrotic myofibroblasts is a crucial process for fibrotic remodeling in IPF. Recent findings show participation of autophagy/mitophagy, part of the lysosomal degradation machinery, in IPF pathogenesis. Mitophagy has been implicated in myofibroblast differentiation through regulating mitochondrial reactive oxygen species (ROS)-mediated platelet-derived growth factor receptor (PDGFR) activation...
June 2, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28574506/role-of-atg5-dependent-cell-death-in-the-embryonic-development-of-bax-bak-double-knockout-mice
#10
Satoko Arakawa, Masatsune Tsujioka, Tatsushi Yoshida, Hajime Tajima-Sakurai, Yuya Nishida, Yosuke Matsuoka, Ikuyo Yoshino, Yoshihide Tsujimoto, Shigeomi Shimizu
Programmed cell death, which is required for the development and homeostasis of metazoans, includes mechanisms such as apoptosis, autophagic cell death, and necrotic (or type III) death. Members of the Bcl2 family regulate apoptosis, among which Bax and Bak act as a mitochondrial gateway. Although embryonic fibroblasts from Bax/Bak double-knockout (DKO) mice are resistant to apoptosis, we previously demonstrated that these cells die through an autophagy-dependent mechanism in response to various types of cellular stressors...
June 2, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28535644/-effect-of-neuroglobin-on-oxygen-glucose-deprivation-and-reoxygenation-induced-autophagy-in-a-human-neuroblastoma-cell-line
#11
S Y Deng, Y H Ai, H Gong, L Wu, C X Chen, Y M Wang, Z Y Liu, L Huang, Q Y Peng, L N Zhang
Objective: To investigate the effect of neuroglobin on oxygen-glucose deprivation and reoxygenation (OGD/R) induced autophagy in a human neuroblastoma cell line (SH-SY5Y). Methods: SH-SY5Y cells were transfected with plasmids (or vector) to establish a stable cell line of NGB overexpression (OE). After treated with OGD/R, cells were collected for the analyses of mRNA (Atg5, Atg7, BECN1 and FUNDC1) and protein levels of LC3. Furthermore, mitochondrial and cytosolic fractions were isolated for protein levels of PINK1 and Parkin...
May 23, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28521613/how-autophagy-eats-large-mitochondria-autophagosome-formation-coupled-with-mitochondrial-fragmentation
#12
Shun-Ichi Yamashita, Tomotake Kanki
Mitochondrial autophagy (mitophagy) is thought to be a multi-step pathway wherein mitochondria are first divided into small fragments, which are subsequently recognized by the phagophore. DNM1L (dynamin 1 like) plays a pivotal role in mitochondrial division; however, its role in mitophagy remains controversial. In our recent study, we examined the contribution of DNM1L to mitophagy and showed that mitophagy and mitochondrial division occur even in DNM1L-defective cells. Furthermore, time-lapse imaging of mitophagy showed that DNM1L-independent mitochondrial division occurs concomitantly with autophagosome formation...
May 4, 2017: Autophagy
https://www.readbyqxmd.com/read/28456949/monitoring-of-atg5-independent-mitophagy
#13
Satoko Arakawa, Shinya Honda, Satoru Torii, Masatsune Tsujioka, Shigeomi Shimizu
Mitophagy is a mitochondrial quality control mechanism where damaged and surplus mitochondria are removed by autophagy. There are at least two different mammalian autophagy pathways: the Atg5-dependent conventional pathway and an Atg5-independent alternative pathway; the latter is involved in the erythrocyte mitophagy. In this chapter we describe the various experimental approaches to assess Atg5-indepedndent mitophagy in mammalian cells.
April 30, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28407242/the-role-of-autophagy-in-pro-inflammatory-responses-of-microglia-activation-via-mitochondrial-reactive-oxygen-species-in%C3%A2-vitro
#14
Junli Ye, Zhongxin Jiang, Xuehong Chen, Mengyang Liu, Jing Li, Na Liu
Microglia over-activation contributes to neurodegenerative processes by neurotoxin factors and pro-inflammatory molecules of pro-inflammatory processes. Mitochondrial reactive oxygen species (ROS) and autophagy pathway might be involved in microglial activation, but the underlying mechanism is unclear. Here, we regulated autophagy pathway of microglia in vitro by autophagy inhibition (3-methyladenine treatment, siRNA-Beclin 1 or siRNA-ATG5 transfection) or induction (rapamycin treatment) in murine microglial BV-2 cells or cultured primary mouse microglial cells...
July 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28388958/pre-incubation-with-hucmsc-exosomes-prevents-cisplatin-induced-nephrotoxicity-by-activating-autophagy
#15
Bingying Wang, Haoyuan Jia, Bin Zhang, Juanjuan Wang, Cheng Ji, Xueming Zhu, Yongmin Yan, Lei Yin, Jing Yu, Hui Qian, Wenrong Xu
BACKGROUND: The administration of cisplatin is limited due to its nephrotoxic side effects, and prevention of this nephrotoxicity of cisplatin is difficult. Mesenchymal stem cell (MSC)-derived exosomes have been implicated as a novel therapeutic approach for tissue injury. In this study, we demonstrated that the pretreatment of human umbilical cord MSC-derived exosomes (hucMSC-Ex) can prevent the development of cisplatin-induced renal toxicity by activation of autophagy in vitro and in vivo...
April 8, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28358377/mitochondrial-complex-i-inhibition-triggers-a-mitophagy-dependent-ros-increase-leading-to-necroptosis-and-ferroptosis-in-melanoma-cells
#16
Farhan Basit, Lisanne Mpe van Oppen, Laura Schöckel, Hasse M Bossenbroek, Sjenet E van Emst-de Vries, Johannes Cw Hermeling, Sander Grefte, Charlotte Kopitz, Melanie Heroult, Peter Hgm Willems, Werner Jh Koopman
Inhibition of complex I (CI) of the mitochondrial respiratory chain by BAY 87-2243 ('BAY') triggers death of BRAF(V600E) melanoma cell lines and inhibits in vivo tumor growth. Here we studied the mechanism by which this inhibition induces melanoma cell death. BAY treatment depolarized the mitochondrial membrane potential (Δψ), increased cellular ROS levels, stimulated lipid peroxidation and reduced glutathione levels. These effects were paralleled by increased opening of the mitochondrial permeability transition pore (mPTP) and stimulation of autophagosome formation and mitophagy...
March 30, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28334504/regulated-in-development-and-dna-damage-response-1-deficiency-impairs-autophagy-and-mitochondrial-biogenesis-in-articular-cartilage-and-increases-the-severity-of-experimental-osteoarthritis
#17
Oscar Alvarez-Garcia, Tokio Matsuzaki, Merissa Olmer, Lars Plate, Jeffery W Kelly, Martin K Lotz
OBJECTIVE: Regulated in development and DNA damage response 1 (REDD1) is an endogenous inhibitor of mechanistic target of rapamycin (mTOR) that regulates cellular stress responses. REDD1 expression is decreased in aged and osteoarthritic (OA) cartilage, and it regulates mTOR signaling and autophagy in articular chondrocytes in vitro. This study was undertaken to investigate the effects of REDD1 deletion in vivo using a mouse model of experimental OA. METHODS: OA severity was histologically assessed in 4-month-old wild-type and REDD1(-/-) mice subjected to surgical destabilization of the medial meniscus (DMM)...
July 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28296000/novel-application-of-localized-nanodelivery-of-anti-interleukin-6-protects-organ-transplant-from-ischemia-reperfusion-injuries
#18
Z Solhjou, M Uehara, B Bahmani, O H Maarouf, T Ichimura, C R Brooks, W Xu, M Yilmaz, A Elkhal, S G Tullius, I Guleria, M M McGrath, R Abdi
Ischemia-reperfusion injury (IRI) evokes intragraft 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 (DCs). While autophagy is a survival mechanism for ischemic DCs, it also augments their production of interleukin (IL)-6...
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
#19
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
#20
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
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