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https://www.readbyqxmd.com/read/29343514/trpm2-channel-mediated-regulation-of-autophagy-maintains-mitochondrial-function-and-promotes-gastric-cancer-cell-survival-via-the-jnk-signaling-pathway
#1
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
https://www.readbyqxmd.com/read/29317636/the-expression-of-inhibitor-of-bruton-s-tyrosine-kinase-gene-is-progressively-up-regulated-in-the-clinical-course-of-chronic-lymphocytic-leukaemia-conferring-resistance-to-apoptosis
#2
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
https://www.readbyqxmd.com/read/29312568/transcriptional-response-to-hypoxic-stress-in-melanoma-and-prognostic-potential-of-gbe1-and-bnip3
#3
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
https://www.readbyqxmd.com/read/29287594/comprehensive-molecular-biomarker-identification-in-breast-cancer-brain-metastases
#4
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
https://www.readbyqxmd.com/read/29250140/effects-of-dimethyl-carbonate-induced-autophagic-activation-on-follicular-development-in-the-mouse-ovary
#5
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
https://www.readbyqxmd.com/read/29230415/hypoxia-induces-apoptosis-through-hif-1%C3%AE-signaling-pathway-in-human-uterosacral-ligaments-of-pelvic-organ-prolapse
#6
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-1α (HIF-1α) 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-1α 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
https://www.readbyqxmd.com/read/29228704/role-of-hif-1a-in-regulating-autophagic-cell-survival-during-cerebral-ischemia-reperfusion-in-rats
#7
Yongqing Guo
Hypoxia-inducible factor-1a (HIF-1a) plays a beneficial role during cerebral ischemia reperfusion (IR), but the underlying molecular mechanisms are not completely understood. Here, we aimed to investigate the effects and molecular regulation of HIF-1a on brain cell apoptosis and autophagy during IR. We found that augmentation of HIF-1a in re-perfused hematopoietic cells significantly reduced brain damage, alleviated brain edema and improved neural function during IR, seemingly through two HIF-1a target genes BNIP3 and NIX, which were critical regulators for cell apoptosis and autophagic cell survival...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29223809/cadmium-induces-bnip3-dependent-autophagy-in-chicken-spleen-by-modulating-mir-33-ampk-axis
#8
Menghao Chen, Xiaojing Li, Ruifeng Fan, Jie Yang, Xi Jin, Sattar Hamid, Shiwen Xu
Cadmium (Cd), a widespread environmental pollutant, has toxic effects on organs including spleen. However, the underlying mechanisms of Cd induced spleen toxicity and the roles of micro-RNA (miRNA) in this process remain poorly understood. To investigate this, cadmium chloride (CdCl2, 10 mg/kg) was administered in the diet of chickens for 90 days. Electron microscopy, qPCR and Western blot were performed. Results showed that Cd exposure suppressed miR-33-5q which increased the levels of AMPK. Subsequently, significant decrease in AKT/mTOR signaling and HSP70 were observed...
December 6, 2017: Chemosphere
https://www.readbyqxmd.com/read/29218081/tetramethylpyrazine-phosphate-and-borneol-combination-therapy-synergistically-attenuated-ischemia-reperfusion-injury-of-the-hypothalamus-and-striatum-via-regulation-of-apoptosis-and-autophagy-in-a-rat-model
#9
Bin Yu, Ming Ruan, Tao Liang, Shi-Wen Huang, Sheng-Jin Liu, Hai-Bo Cheng, Xiang-Chun Shen
The combination of tetramethylpyrazine (TMP) and borneol (BO) has shown promise for treatment of cerebral ischemia in clinical and experimental studies. However, the mechanism for the synergistic effect of these compounds is unclear. In this study, global cerebral ischemia-reperfusion (GCIR) was induced in rats that were subsequently treated with tetramethylpyrazine phosphate (TMPP) (13.3 mg/kg), BO (0.16 g/kg), or the combination TMPP + BO. Neuronal ultrastructure and intracellular calcium [Ca2+]i levels were evaluated in hypothalamus and striatum...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29207102/lncrna-tug1-serves-an-important-role-in-hypoxia-induced-myocardial-cell-injury-by-regulating-the-mir%C3%A2-145%C3%A2-5p%C3%A2-binp3-axis
#10
Zhongwei Wu, Shengji Zhao, Chunfu Li, Chaoquan Liu
The aim of the present study was to investigate the function of long non‑coding RNA TUG1 in hypoxia‑induced myocardial cell injury and to explore the potential molecular mechanisms. The cardiomyocyte cell line H9c2 was cultured under hypoxic and normoxic conditions. TUG1 expression under hypoxic conditions was then detected. The effects of TUG1 overexpression on viability, apoptosis, migration and invasion were assayed. In addition, the microRNA (miR)‑145‑5p expression was detected. Following H9c2 cell transfection with miR‑145‑5p mimics, the H9c2 cell viability, apoptosis, migration and invasion were also detected...
November 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29206300/effects-of-mtor-nf-%C3%AE%C2%BAb-signaling-pathway-and-high-thoracic-epidural-anesthesia-on-myocardial-ischemia-reperfusion-injury-via-autophagy-in-rats
#11
Wei-Qiang Huang, Jian-Lin Wen, Ri-Qi Lin, Peng Wei, Feng Huang
We investigated the role of mammalian target of rapamycin/nuclear factor-kappa B (mTOR/NF-κB) signaling pathway in high thoracic epidural anesthesia (HTEA) against myocardial ischemia-reperfusion (I/R) injury in rats. The rat model of myocardial I/R injury was established. Ninety rats were divided into the normal, sham, I/R, eHTEA, the PDTC and HTEA + PDTC groups. ELISA was applied to detect cardiac function indexes. HE staining was conducted to observe histopathological changes of myocardial tissues, and TTC staining was performed to detect the myocardial infarction size...
December 5, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29167529/liver-specific-deletion-of-ror%C3%AE-aggravates-diet-induced-nonalcoholic-steatohepatitis-by-inducing-mitochondrial-dysfunction
#12
Hyeon-Ji Kim, Yong-Hyun Han, Hyelin Na, Ju-Yeon Kim, Taewook Kim, Hye-Jin Kim, Chanseok Shin, Jung Weon Lee, Mi-Ock Lee
Mitochondrial dysfunction may play a key role in the progression of steatosis to nonalcoholic steatohepatitis (NASH); however, the molecular mechanism that controls the structure and function of mitochondria in NASH is not clearly understood. Here, we demonstrated that RORα is a regulator of expression of Bnip3 and PGC-1α, and thereby enhances mitochondrial quality. First, we observed that liver-specific RORα knockout mice (RORα-LKO) were more susceptible to high-fat diet-induced NASH compared with control, probably due to mitochondrial dysfunction...
November 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29167125/mesenchymal-stem-cells-reduce-hypoxia-induced-apoptosis-in-alveolar-epithelial-cells-by-modulating-hif-and-ros-hypoxic-signalings
#13
Olivier Bernard, Florence Jeny, Yurdagul Uzunhan, Elisabetta Dondi, Rahma Terfous, Rabab Label, Angela Sutton, Jérôme Larghero, Valérie Vanneaux, Hilario Nunes, Emilie Boncoeur, Carole Planès, Nicolas Dard
Distal lung diseases such as pulmonary fibrosis or acute lung injury are commonly associated with local alveolar hypoxia that may be deleterious through the stimulation of alveolar epithelial cell (AEC) apoptosis. In various murine models of alveolar injury, administration of allogenic human mesenchymal stem cells (hMSC) exerts an overall protective paracrine effect limiting lung inflammation and fibrosis. However, the precise mechanisms on lung cells themselves remain poorly understood. Here we investigated whether hMSC conditioned medium (hMSC-CM) would protect AECs from hypoxia-induced apoptosis and the mechanisms involved in this cytoprotective effect...
November 22, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29149759/dusp1-alleviates-cardiac-ischemia-reperfusion-injury-by-suppressing-the-mff-required-mitochondrial-fission-and-bnip3-related-mitophagy-via-the-jnk-pathways
#14
Qinhua Jin, Ruibing Li, Nan Hu, Ting Xin, Pingjun Zhu, Shunying Hu, Sai Ma, Hong Zhu, Jun Ren, Hao Zhou
Mitochondrial fission and selective mitochondrial autophagy (mitophagy) form an essential axis of mitochondrial quality control that plays a critical role in the development of cardiac ischemia-reperfusion (IR) injury. However, the precise upstream molecular mechanism of fission/mitophagy remains unclear. Dual-specificity protein phosphatase1 (DUSP1) regulates cardiac metabolism, but its physiological contribution in the reperfused heart, particularly its influence on mitochondrial homeostasis, is unknown. Here, we demonstrated that cardiac DUSP1 was downregulated following acute cardiac IR injury...
November 6, 2017: Redox Biology
https://www.readbyqxmd.com/read/29137361/downregulation-of-mir-199a-5p-promotes-prostate-adeno-carcinoma-progression-through-loss-of-its-inhibition-of-hif-1%C3%AE
#15
Jinjing Zhong, Rui Huang, Zhengzheng Su, Mengni Zhang, Miao Xu, Jing Gong, Ni Chen, Hao Zeng, Xueqin Chen, Qiao Zhou
Hypoxia-inducible factor-1 alpha (HIF-1α) plays key roles in cell survival under both hypoxia and normoxia conditions. Regulation of HIF-1α is complex and involves numerous molecules and pathways, including post-transcriptional regulation by microRNAs (miRNAs). Although upregulation of HIF-1α has been shown to promote prostate adenocarcinoma (PCa) progression, the mechanism by which miRNAs modulate HIF-1α in prostate cancer has not been clarified. Here, we show that miR-199a-5p is underexpressed in prostate adenocarcinoma...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29131087/deferoxamine-induced-migration-and-odontoblast-differentiation-via-ros-dependent-autophagy-in-dental-pulp-stem-cells
#16
Xuan Wang, Tian Tian Wu, Long Jiang, Du Rong, Ya Qin Zhu
BACKGROUND/AIMS: As a vital degradation and recycling system, autophagy plays an essential role in regulating the differentiation of stem cells. We previously showed that iron chelator deferoxamine (DFO) could promote the repair ability of dental pulp stem cells (DPSCs). Here, we investigated the effect of DFO in autophagy and the role of autophagy in regulating the migration and odontoblast differentiation of DPSCs. METHODS: Transmission electron microscopy, immunofluorescence staining and western blotting were performed to evaluate the autophagic activity of DPSCs...
November 1, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29093680/mechanistic-study-of-bakuchiol-induced-anti-breast-cancer-stem-cell-and-in-vivo-anti-metastasis-effects
#17
Li Li, Chi C Liu, Xueping Chen, Shisan Xu, Sinai Hernandez Cortes-Manno, Shuk H Cheng
Cancer stem cells are involved in cancer establishment, progression, and resistance to current treatments. We demonstrated the in vitro and in vivo anti-breast cancer effect of bakuchiol in a previous study. However, the ability of bakuchiol to target breast cancer stem cells (BCSCs) and inhibit breast cancer metastasis remains unknown. In the current study, we used the cell surface markers CD44 and CD24 to distinguish BCSCs from MCF-7 cells. Bakuchiol inhibited mammosphere formation and aldehyde dehydrogenase activity in BCSCs...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29063978/mst1-regulates-colorectal-cancer-stress-response-via-inhibiting-bnip3-related-mitophagy-by-activation-of-jnk-p53-pathway
#18
Qi Li, Feng Qi, Xiangchao Meng, Chenpei Zhu, Yingtang Gao
The Hippo-Mst1 pathway is associated with tumor development and progression. However, little evidence is available for its role in colorectal cancer (CRC) stress response via mitochondrial homeostasis. In this study, we conducted gain-of function assay about Mst1 in CRC via adenovirus transfection. Then, cellular viability and apoptosis were measured via MTT, TUNEL assay, and typan blue staining. Mitochondrial function was detected via JC1 staining, mPTP opening assay, and immunofluorescence of cyt-c. Mitophagy was observed via western blots and immunofluorescence...
October 24, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/29045486/thiamine-deficiency-activates-hypoxia-inducible-factor-1%C3%AE-to-facilitate-pro-apoptotic-responses-in-mouse-primary-astrocytes
#19
Kristy Zera, Jason Zastre
Thiamine is an essential enzyme cofactor required for proper metabolic function and maintenance of metabolism and energy production in the brain. In developed countries, thiamine deficiency (TD) is most often manifested following chronic alcohol consumption leading to impaired mitochondrial function, oxidative stress, inflammation and excitotoxicity. These biochemical lesions result in apoptotic cell death in both neurons and astrocytes. Comparable histological injuries in patients with hypoxia/ischemia and TD have been described in the thalamus and mammillary bodies, suggesting a congruency between the cellular responses to these stresses...
2017: PloS One
https://www.readbyqxmd.com/read/29030976/synergistic-effect-of-hif-1%C3%AE-and-foxo3a-trigger-cardiomyocyte-apoptosis-under-hyperglycemic-ischemia-condition
#20
Ya-Fang Chen, Sudhir Pandey, Cecilia Hsuan Day, Yu-Feng Chen, Ai-Zhi Jiang, Tsung-Jung Ho, Ray-Jade Chen, Vijaya PadmaViswanadha, Wei-Wen Kuo, Chih-Yang Huang
Cardiomyocyte death is an important pathogenic feature of ischemia and heart failure. Through this study, we showed the synergistic role of HIF-1α and FoxO3a in cardiomyocyte apoptosis subjected to hypoxia plus elevated glucose levels. Using gene specific small interfering RNAs (siRNA), semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR), western blot, immunofluorescence, nuclear and cytosolic localization and TUNEL assay techniques, we determined that combined function of HIF-1α and FoxO3a under high glucose plus hypoxia condition lead to enhanced expression of BNIP3 inducing cardiomyocyte death...
October 14, 2017: Journal of Cellular Physiology
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