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Naho Hirayama, Toshihiko Aki, Takeshi Funakoshi, Kanako Noritake, Kana Unuma, Koichi Uemura
Paraquat (PQ) is an herbicide that was once used worldwide, but is now prohibited in many nations due to its high toxicity to humans. However, there are still rare cases of the fetal intoxication of PQ, which was purchased prior to the prohibition in Japan. In this study, several cell death pathways, the mitochondrial stress response, and autophagy were examined in SH-SY5Y cells exposed to PQ. The results reveal the decrease of a mitochondrial stress sensitive-BNIP3 (Bcl-2/adenovirus E1B 19-kDa-interacting protein 3) protein, the suppression of autophagic flux, and the lack of apoptosis as well as other regulated forms of necrosis, such as necroptosis and ferroptosis...
2018: Journal of Toxicological Sciences
Yang Yuan, Shan-Shan Pan
BACKGROUND: Late exercise preconditioning (LEP) is confirmed to have a protective effect on acute cardiovascular stress. However, the mechanisms by which mitophagy participates in EP-induced cardioprotection remain unclear. LEP may involve mitophagy mediated by the receptors PARK2 gene-encoded E3 ubiquitin ligase (Parkin) and BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (Bnip3) to scavenge damaged mitochondria. METHODS: Our exercise preconditioning (EP) protocol involved four 10-minute periods of running, separated by 10-minute recovery intervals, plus a period of exhaustive running at 24 hours after EP...
March 9, 2018: Journal of Cardiovascular Pharmacology
Johan Spetz, Nils Rudqvist, Britta Langen, Toshima Z Parris, Johanna Dalmo, Emil Schüler, Bo Wängberg, Ola Nilsson, Khalil Helou, Eva Forssell-Aronsson
INTRODUCTION: Patients with neuroendocrine tumors expressing somatostatin receptors are often treated with177 Lu-octreotate. Despite being highly effective in animal models,177 Lu-octreotate-based therapies in the clinical setting can be optimized further. The aims of the study were to identify and elucidate possible optimization venues for177 Lu-octreotate tumor therapy by characterizing transcriptional responses in the GOT1 small intestine neuroendocrine tumor model in nude mice. METHODS: GOT1-bearing female BALB/c nude mice were intravenously injected with 15 MBq177 Lu-octreotate (non-curative amount) or mock-treated with saline solution...
February 6, 2018: Nuclear Medicine and Biology
Bjorn T Tam, Angus P Yu, Eric W Tam, Douglas A Monks, Xu P Wang, Xiao M Pei, Su P Koh, Thomas K Sin, Helen K W Law, Felix N Ugwu, Rashmi Supriya, Benjamin Y Yung, Shea P Yip, S C Wong, Lawrence W Chan, Christopher W Lai, Pin Ouyang, Parco M Siu
Pressure-induced injury (PI), such as a pressure ulcer, in patients with limited mobility is a healthcare issue worldwide. PI is an injury to skin and its underlying tissue such as skeletal muscle. Muscle compression, composed of mechanical deformation of muscle and external load, leads to localized ischemia and subsequent unloading reperfusion and, hence, a pressure ulcer in bed-bound patients. Although the gross factors involved in PI have been identified, little is known about the exact disease mechanism or its links to apoptosis, autophagy and inflammation...
February 27, 2018: Scientific Reports
Jessica Sacks, Anny Mulya, Ciaran E Fealy, Hazel Huang, John D Mosinski, Mangesh R Pagadala, Hideharu Shimizu, Esam Batayyah, Philip R Schauer, Stacy A Brethauer, John P Kirwan
Bariatric surgery provides significant and durable improvements in glycemic control and hepatic steatosis, but the underlying mechanisms that drive improvements in these metabolic parameters remain to be fully elucidated. Recently, alterations in mitochondrial morphology have shown a direct link to nutrient adaptations in obesity. Here, we evaluate the effects of Roux-en-Y gastric bypass (RYGB) surgery on markers of liver mitochondrial dynamics in a diet-induced obesity Sprague-Dawley (SD) rat model. Livers were harvested from adult male SD rats 90-days after either Sham or RYGB surgery and continuous high-fat feeding...
February 2018: Physiological Reports
Yufei Song, Yu Du, Wenying Zou, Yan Luo, Xiaojie Zhang, Jianliang Fu
Chronic cerebral hypoperfusion (CCH) plays an insidious role in the development of cognitive impairment. Considerable evidence suggests that Diabetes Mellitus (DM) as a vascular risk factor may exacerbate CCH and is closely related to cognitive decline. Dysregulation of autophagy is known to be associated with the pathogenesis of neurodegenerative diseases such as Alzheimer's disease. To elucidate the role of autophagy in CCH- and/or DM-related pathogenesis, mouse neuroblastoma Neuro-2a cells were exposed to hypoxia and/or high glucose for 48 h, mimicking CCH complicated with DM pathologies...
February 19, 2018: Scientific Reports
Ruoqiu Fu, Qin Deng, Hongwei Zhang, Xiaoye Hu, Yunong Li, Yanxia Liu, Jinjiao Hu, Qingsong Luo, Yanhao Zhang, Xiuxing Jiang, Lirong Li, Chong Yang, Ning Gao
Increasing evidences reveal that autophagy inhibitor could enhance the effect of chemotherapy to cancer. However, few autophagy inhibitors are currently approved for clinical application in humans. Berbamine (BBM) is a natural compound extracted from traditional Chinese medicine that is widely used for treatment of a variety of diseases without any obvious side effects. Here we found that BBM is a novel auophagy inhibitor, which potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human breast cancer cells...
February 14, 2018: Cell Death & Disease
Rui Chen, Jiehua Xu, Yanling She, Ting Jiang, Shanyao Zhou, Huacai Shi, Cheng Li
Necrostatin-1 (Nec-1) is a selective and potent allosteric inhibitor of necroptosis by specifically inhibiting the activity of receptor‑interacting protein (RIP) 1 kinase. The aim of the present study was to determine the effect of Nec‑1 on an anoxia model comprising mouse skeletal C2C12 myotubes. In the present study, a hypoxic mimetic reagent, cobalt chloride (CoCl2), was used to induce hypoxia in C2C12 myotubes. The cytotoxic effects of CoCl2‑induced hypoxia were determined by a Cell Counting kit‑8 assay and flow cytometry...
February 6, 2018: International Journal of Molecular Medicine
Minwei He, Kangqi Li, Chuanfei Yu, Bingfeng Lv, Ning Zhao, Jinhai Deng, Lulu Cao, He Huang, Ang Yin, Taiping Shi, Lu Wang
FUZ is regarded as a planar cell polarity effector that controls multiple cellular processes during vertebrate development. However, the role of FUZ in tumor biology remains poorly studied. Our purpose of this study is to discover the physiological effects and mechanism of FUZ in non-small-cell lung cancer (NSCLC) in vitro. With the help of bioinformatics analysis, we noticed that the expression level of FUZ negatively correlates with prognosis of NSCLC patients. Exogenous FUZ expression markedly promoted cell proliferation of NSCLC cells...
February 5, 2018: Life Sciences
Rathinavel Ashokkumar, Sankar Jamuna, M S Sakeena Sadullah, S Niranjali Devaraj
The molecular mechanisms involved in ER stress-induced post myocardial injury remain elusive. In this study, we have investigated the molecular mechanism of ER stress-mediated myocyte death in Isoproterenol (ISO) induced myocardial infarction and its inhibition by a potent anti oxidant and anti-apoptotic bioflavonoid, Vitexin. ISO mediated apoptosis was found to be associated with ER permeabilization and characterized by enhanced production of ROS, activation of caspase-3, modulation of Bcl2 family proteins and activation of bnip3...
February 5, 2018: Biochemical and Biophysical Research Communications
Shiro Matsubara, Kota Bokuda, Yuri Asano, Ryo Morishima, Keizo Sugaya, Kazuhito Miyamoto, Reiji Koide, Takashi Komori, Shigeaki Suzuki, Ichizo Nishino
Immune-mediated necrotizing myopathy (IMNM) associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) autoantibodies occurs in patients both with and without history of statin-intake. The mechanisms of muscle fiber degeneration in this condition remain unknown. We studied pathological changes in muscle biopsies from three patients lacking history of statin-intake. Ultrastructural observations showed accumulation of degenerating mitochondria, glycogen granules and autophagic vacuoles, forming large composites in three cases, along with various nonspecific changes...
January 11, 2018: Neuromuscular Disorders: NMD
Michael I Koukourakis, Christos Kakouratos, Dimitra Kalamida, Achilleas Mitrakas, Stamatia Pouliliou, Erasmia Xanthopoulou, Evdokia Papadopoulou, Virginia Fasoulaki, Alexandra Giatromanolaki
Apalutamide (ARN-509) is an antiandrogen that binds selectively to androgen receptors (AR) and does not show antagonist-to-agonist switch like bicalutamide. We compared the activity of ARN versus bicalutamide on prostate cancer cell lines. The 22Rv1, PC3, and DU145 cell lines were used to study the effect of ARN and bicalutamide on the expression cytoplasmic/nuclear kinetics of AR, AR-V7 variant, phosphorylated AR, as well as the levels of the AR downstream proteins prostate-specific antigen and TMPRSS2, under exposure to testosterone and/or hypoxia...
January 29, 2018: Anti-cancer Drugs
Michael L Rossetti, Jennifer L Steiner, Bradley S Gordon
Androgen-deficiency promotes muscle atrophy in part by increasing autophagy-mediated muscle protein breakdown during the fasted state, but factors contributing to this remain undefined. To identify novel factors, mice were subjected to sham or castration surgery. Seven-weeks post-surgery, mice were fasted overnight, refed for 30 min, and fasted another 4.5 h before sacrifice. BNIP3-mediated turnover of mitochondria was increased within the atrophied tibialis anterior (TA) of castrated mice and related to the magnitude of muscle atrophy and autophagy activation (i...
January 29, 2018: Molecular and Cellular Endocrinology
Chao Yuan, Luqiao Pu, Zhiliang He, Jian Wang
The present study aimed to investigate the molecular mechanisms of cyclic stretch-induced apoptosis in human intervertebral disc cartilage endplate-derived stem cells (CESCs). CESCs were stretched by the Flexercell-4000™ Tension Plus system, the effect on cell viability was measured by a Cell Counting Kit-8 assay, while cell apoptosis was detected by flow cytometry. Western blot analysis was used to evaluate the expression of B-cell lymphoma 2 (Bcl-2)/adenovirus E1B 19 kDa interacting protein 3 (BNIP3), Bcl-2, Bcl-2 homologous antagonist killer (Bak), Bcl-2-associated X protein (Bax), Bcl extra large (Bcl-xl) and the activity of caspase-3, while Z-VAD-FMK was used to inhibit caspase-3...
January 2018: Experimental and Therapeutic Medicine
Shekoufeh Almasi, Barry E Kennedy, Mariam El Aghil, Andra M Sterea, Shashi Gujar, Santiago Partida-Sánchez, Yassine El Hiani
A lack of effective treatment is one of the main factors contributing to gastric cancer-related death. Discovering effective targets and understanding their underlying anticancer mechanism is key to achieving the best response to treatment and to limiting side effects. Although recent studies have shown that the cation channel transient receptor potential melastatin-2 (TRPM2) is crucial for cancer cell survival, the exact mechanism remains unclear, limiting its therapeutic potential. Here, using molecular and functional assays, we investigated the role of TRPM2 in survival of gastric cancer cells...
January 17, 2018: Journal of Biological Chemistry
Francesco Albano, Federico Chiurazzi, Selena Mimmi, Eleonora Vecchio, Arianna Pastore, Clementina Cimmino, Camilla Frieri, Enrico Iaccino, Antonio Pisano, Gaetanina Golino, Giuseppe Fiume, Massimo Mallardo, Giuseppe Scala, Ileana Quinto
Chronic lymphocytic leukaemia (CLL) is the most common B-cell malignancy with a variable clinical outcome. Biomarkers of CLL progression are required for optimising prognosis and therapy. The Inhibitor of Bruton's tyrosine kinase-isoform α (IBTKα) gene encodes a substrate receptor of Cullin 3-dependent E3 ubiquitin ligase, and promotes cell survival in response to the reticulum stress. Searching for novel markers of CLL progression, we analysed the expression of IBTKα in the peripheral blood B-cells of CLL patients, before and after first line therapy causing remission...
January 9, 2018: Cell Death & Disease
Stéphanie Buart, Stéphane Terry, Muhammad Z Noman, Emilie Lanoy, Céline Boutros, Paul Fogel, Philippe Dessen, Guillaume Meurice, Yann Gaston-Mathé, Philippe Vielh, Séverine Roy, Emilie Routier, Virginie Marty, Sophie Ferlicot, Luc Legrès, Morad El Bouchtaoui, Nyam Kamsu-Kom, Jane Muret, Eric Deutsch, Alexander Eggermont, Jean-Charles Soria, Caroline Robert, Salem Chouaib
Gradients of hypoxia occur in most solid tumors and cells found in hypoxic regions are associated with the most aggressive and therapy-resistant fractions of the tumor. Despite the ubiquity and importance of hypoxia responses, little is known about the variation in the global transcriptional response to hypoxia in melanoma. Using microarray technology, whole genome gene expression profiling was first performed on established melanoma cell lines. From gene set enrichment analyses, we derived a robust 35 probes signature (hypomel for HYPOxia MELanoma) associated with hypoxia-response pathways, including 26 genes up regulated, and 9 genes down regulated...
December 12, 2017: Oncotarget
Hans-Juergen Schulten, Mohammed Bangash, Sajjad Karim, Ashraf Dallol, Deema Hussein, Adnan Merdad, Fatma K Al-Thoubaity, Jaudah Al-Maghrabi, Awatif Jamal, Fahad Al-Ghamdi, Hani Choudhry, Saleh S Baeesa, Adeel G Chaudhary, Mohammed H Al-Qahtani
BACKGROUND: Breast cancer brain metastases (BCBM) develop in about 20-30% of breast cancer (BC) patients. BCBM are associated with dismal prognosis not at least due to lack of valuable molecular therapeutic targets. The aim of the study was to identify new molecular biomarkers and targets in BCBM by using complementary state-of-the-art techniques. METHODS: We compared array expression profiles of three BCBM with 16 non-brain metastatic BC and 16 primary brain tumors (prBT) using a false discovery rate (FDR) p < 0...
December 29, 2017: Journal of Translational Medicine
Zonghao Tang, Zhenghong Zhang, Yedong Tang, Lingbin Qi, Fafu Yang, Zhengchao Wang
Dimethyl carbonate (DMC) is a widely used industrial chemical, which may be increasingly used in the future. However, its toxicity profile remains largely unknown. The present study was designed to investigate the effects of DMC exposure on the ovaries and the effect of autophagy activation on follicular development. Rats were randomly divided into a control group and low, medium and high dose DMC groups (all n=10). Histological analyses identified no marked differences in the rate of apoptosis between the control and low dose groups; however, marked apoptosis occurred in the medium and high dose groups...
December 2017: Experimental and Therapeutic Medicine
Xinrui Zhao, Congcong Ma, Rui Li, Jing Xue, Lidong Liu, Peishu Liu
The purpose of this study is to evaluate the expression of hypoxia-inducible factor-1 α (HIF-1 α ) in women uterosacral ligament tissues with pelvic organ prolapse and women with normal uterine support structures and illuminate its relationship with apoptosis. Samples were collected from 38 women with pelvic organ prolapse and 31 age matched controls. The expression levels of HIF-1 α and BNIP3 in the uterosacral ligaments were measured using immunohistochemistry, qRT-PCR, and Western blot. To assess apoptosis we performed TUNEL assay and Western blot analyses...
2017: BioMed Research International
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