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https://www.readbyqxmd.com/read/28222492/discovery-of-mieap-regulated-mitochondrial-quality-control-as-a-new-function-of-tumor-suppressor-p53
#1
REVIEW
Yasuyuki Nakamura, Hirofumi Arakawa
The tumor suppressor p53 gene is frequently mutated in human cancers, and the p53 protein suppresses cancer. However, the mechanism behind the p53-mediated tumor suppression is still unclear. Recently, Mieap (the mitochondria-eating protein) was identified as a p53-inducible protein. Mieap induces the accumulation of lysosomal proteins within mitochondria (MALM: Mieap-induced accumulation of lysosome-like organelles within mitochondria) in response to mitochondrial damage, and eliminates the oxidized mitochondrial proteins to repair unhealthy mitochondria...
February 21, 2017: Cancer Science
https://www.readbyqxmd.com/read/28216619/15-deoxy-%C3%AE-12-14-prostaglandin-j2-alleviates-hepatic-ischemia-reperfusion-injury-in-mice-via-inducing-antioxidant-response-and-inhibiting-apoptosis-and-autophagy
#2
Kan Chen, Jing-Jing Li, Sai-Nan Li, Jiao Feng, Tong Liu, Fan Wang, Wei-Qi Dai, Yu-Jing Xia, Jie Lu, Ying-Qun Zhou, Chuan-Yong Guo
Hepatic ischemia-reperfusion (I/R) injury is a common clinical impairment that occurs in many circumstances and leads to poor prognosis. Both apoptosis and autophagy have been shown to contribute to cell death in hepatic I/R injury. 15-Deoxy-Δ(12,14)-prostaglandin J2 (15d-PGJ2) is one of the best-studied anti-inflammatory prostaglandins, which has been verified to exert anti-inflammatory and cell-protective functions in various types of cells and animal models. In this study we explored the effects of 15d-PGJ2 on both apoptosis and autophagy in mouse hepatic I/R injury and its possible mechanisms...
February 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28213823/long-term-resistance-exercise-induced-muscular-hypertrophy-is-associated-with-autophagy-modulation-in-rats
#3
Insu Kwon, Yongchul Jang, Joon-Yong Cho, Young C Jang, Youngil Lee
Elevation of anabolism and concurrent suppression of catabolism are critical metabolic adaptations for muscular hypertrophy in response to resistance exercise (RE). Here, we investigated if RE-induced muscular hypertrophy is acquired by modulating a critical catabolic process autophagy. Male Wistar Hannover rats (14 weeks old) were randomly assigned to either sedentary control (SC, n = 10) or resistance exercise (RE, n = 10). RE elicited significant hypertrophy of flexor digitorum profundus (FDP) muscles in parallel with enhancement in anabolic signaling pathways (phosphorylation of AKT, mTOR, and p70S6K)...
February 17, 2017: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/28207880/skeletal-muscle-metabolic-adaptations-to-endurance-exercise-training-are-attainable-in-mice-with-simvastatin-treatment
#4
William M Southern, Anna S Nichenko, Daniel D Shill, Corey C Spencer, Nathan T Jenkins, Kevin K McCully, Jarrod A Call
We tested the hypothesis that a 6-week regimen of simvastatin would attenuate skeletal muscle adaptation to low-intensity exercise. Male C57BL/6J wildtype mice were subjected to 6-weeks of voluntary wheel running or normal cage activities with or without simvastatin treatment (20 mg/kg/d, n = 7-8 per group). Adaptations in in vivo fatigue resistance were determined by a treadmill running test, and by ankle plantarflexor contractile assessment. The tibialis anterior, gastrocnemius, and plantaris muscles were evaluated for exercised-induced mitochondrial adaptations (i...
2017: PloS One
https://www.readbyqxmd.com/read/28195146/the-inhibition-of-lung-cancer-cell-migration-by-ahr-regulated-autophagy
#5
Chi-Hao Tsai, Ching-Hao Li, Yu-Wen Cheng, Chen-Chen Lee, Po-Lin Liao, Cheng-Hui Lin, Shih-Hsuan Huang, Jaw-Jou Kang
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is highly expressed in multiple organs and tissues. Whereas AhR mediates the metabolism of xenobiotic and endogenous compounds, its novel function in cancer epithelial-mesenchymal transition (EMT) remains controversial. Autophagy also participates in tumour progression through its functions in cell homeostasis and facilitates adaptation to EMT progression. In the present study, we found that AhR-regulated autophagy positively modulates EMT in non-small cell lung cancer cells...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28167504/inhibition-of-isoprenylcysteine-carboxylmethyltransferase-induces-cell-cycle-arrest-and-apoptosis-through-p21-and-p21-regulated-bnip3-induction-in-pancreatic-cancer
#6
Kanjoormana Aryan Manu, Tin Fan Chai, Jing Tsong Teh, Wan Long Zhu, Patrick J Casey, Mei Wang
Pancreatic cancer remains one of the most difficult to treat human cancers despite recent advances in targeted therapy. Inhibition of Isoprenylcysteine carboxylmethyltransferase (ICMT), an enzyme that post-translationally modifies a group of proteins including several small GTPases, suppresses proliferation of some human cancer cells. However, the efficacy of ICMT inhibition on human pancreatic cancer has not been evaluated. In this study we have evaluated a panel of human pancreatic cancer cell lines and identified those that are sensitive to ICMT inhibition...
February 6, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28151469/bnip3-upregulation-via-stimulation-of-erk-and-jnk-activity-is-required-for-the-protection-of-keratinocytes-from-uvb-induced-apoptosis
#7
Mariko Moriyama, Hiroyuki Moriyama, Junki Uda, Hirokazu Kubo, Yuka Nakajima, Arisa Goto, Takashi Morita, Takao Hayakawa
The human skin has an important role in barrier function. Ultraviolet rays (UV) from sunlight exposure can cause cell apoptosis in the skin epidermis, resulting in the disruption of the barrier. Previously, we have demonstrated that BNIP3 stimulates autophagy in epidermal keratinocytes and has a protective effect in these cells upon UVB irradiation. In this study, we found that the accumulation of reactive oxygen species (ROS) by UVB irradiation was sufficient to trigger the activation of JNK and ERK mitogen-activated protein kinase (MAPK) in human primary epidermal keratinocytes...
February 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28148542/predicting-the-grade-of-dysplasia-of-pancreatic-cystic-neoplasms-using-cyst-fluid-dna-methylation-markers
#8
Tatsuo Hata, Marco Dal Molin, Seung-Mo Hong, Koji Tamura, Masaya Suenaga, Jun Yu, Hiraku Sedogawa, Matthew J Weiss, Christopher L Wolfgang, Anne Marie Lennon, Ralph H Hruban, Michael G Goggins
PURPOSE: Pancreatic cysts are common and pose diagnostic and management challenges. Pancreatic cyst fluid markers have the potential to aid in the management of cysts with concerning imaging findings. Our aim was to evaluate cyst fluid methylated DNA markers for their accuracy for predicting the histologic grade of neoplastic pancreatic cysts. EXPERIMENTAL DESIGN: Pancreatic cyst fluid samples from 183 patients (29 discovery, 154 validation) aspirated after surgical resection were analyzed for methylated DNA at selected genes (SOX17, BNIP3, FOXE1, PTCHD2, SLIT2, EYA4 and SFRP1) using methylation-specific droplet-digital PCR (dd-QMSP)...
February 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28117625/autophagy-influences-the-low-dose-hyper-radiosensitivity-of-human-lung-adenocarcinoma-cells-by-regulating-mlh1
#9
Qiong Wang, Zhuya Xiao, Zhenyu Lin, Jie Zhou, Weihong Chen, Wuyun Jie, Xing Cao, Zhongyuan Yin, Jing Cheng
Purpose To investigate the impact of autophagy on the low-dose hyper-radiosensitivity (HRS) of human lung adenocarcinoma cells via MLH1 regulation. Materials and methods Immunofluorescent staining, Western blotting, and electron microscopy were utilized to detect autophagy in A549 and H460 cells. shRNA was used to silence MLH1 expression. The levels of MLH1, mTOR, p-mTOR, BNIP3, and Beclin-1 were measured by real-time polymerase chain reaction (PCR) and Western blotting. Results A549 cells, which have low levels of MLH1 expression, displayed HRS/induced radioresistance (IRR)...
January 24, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28000962/hypoxia-causes-il-8-secretion-charcot-leyden-crystal-formation-and-suppression-of-corticosteroid-induced-apoptosis-in-human-eosinophils
#10
Linsey M Porter, Andrew S Cowburn, Neda Farahi, John Deighton, Stuart N Farrow, Christine A Fiddler, Jatinder K Juss, Alison M Condliffe, Edwin R Chilvers
BACKGROUND: Inflamed environments are typically hypercellular, rich in pro-inflammatory cytokines, and profoundly hypoxic. While the effects of hypoxia on neutrophil longevity and function have been widely studied, little is known about the consequences of this stimulus on eosinophils. OBJECTIVE: We sought to investigate the effects of hypoxia on several key aspects of eosinophil biology; namely secretion, survival, and their sensitivity to glucocorticosteroids (GCS), agents which normally induce eosinophil apoptosis...
December 21, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27893424/accumulated-promoter-methylation-as-a-potential-biomarker-for-esophageal-cancer
#11
Xianzhen Peng, Hengchuan Xue, Lingshuang Lü, Peiyi Shi, Jianping Wang, Jianming Wang
We performed a two-stage molecular epidemiological study to explore DNA methylation profiles for potential biomarkers of esophageal squamous cell carcinoma (ESCC) in a Chinese population. Infinium Methylation 450K BeadChip was used to identify genes with differentially methylated CpG sites. Sixteen candidate genes were validated by sequencing 1160 CpG sites in their promoter regions using the Illumina MiSeq platform. When excluding sites with negative changes, 10 genes (BNIP3, BRCA1, CCND1, CDKN2A, HTATIP2, ITGAV, NFKB1, PIK3R1, PRDM16 and PTX3) showed significantly different methylation levels among cancer lesions, remote normal-appearing tissues, and healthy controls...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/27886395/popdc1-bves-functions-in-the-preservation-of-cardiomyocyte-viability-while-affecting-rac1-activity-and-bnip3-expression
#12
Vitaly Kliminski, Orit Uziel, Gania Kessler-Icekson
The Popeye domain containing1, also called Bves (Popdc1/Bves), is a transmembrane protein that functions in muscle regeneration, heart rate regulation, hypoxia tolerance, and ischemia preconditioning. The expression of Popdc1/Bves is elevated in cardiomyocytes maintained in serum free defined medium. We hypothesized that Popdc1/Bves is important for cardiomyocyte survival under the stress of serum deprivation and investigated the mechanisms involved. A deficit in Popdc1/Bves, achieved by siRNA-mediated gene silencing, results in cardiomyocyte injury and death, upregulation of the pro-apoptotic protein Bcl-2/adenovirus E1B 19-kDa interacting protein3 (Bnip3), as well as reduction in Rac1-GTPase activity and in Akt phosphorylation...
November 25, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27864279/nutrition-deficiency-promotes-apoptosis-of-cartilage-endplate-stem-cells-in-a-caspase-independent-manner-partially-through-upregulating-bnip3
#13
Zhiliang He, Luqiao Pu, Chao Yuan, Min Jia, Jian Wang
Nutrition deficiency is reported to induce apoptosis of chondrocytes and degeneration of cartilage endplate (CEP) in rabbit. Cartilage endplate stem cells (CESCs) are important for the integrity of structure and function of CEP. Bcl-2/adenovirus E1B 19-kDa-interacting protein 3 (BNIP3) has been reported to regulate apoptosis, autophagy, and cytoprotection. In this study, we aimed to determine whether nutrition deficiency induces apoptosis of CESCs, and whether or not the BNIP3-related pathway is activated in CESCs during nutrition deficiency...
January 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/27862640/long-non-coding-rna-malat1-functions-as-a-mediator-in-cardioprotective-effects-of-fentanyl-in-myocardial-ischemia-reperfusion-injury
#14
Zhi-Hui Zhao, Wei Hao, Qing-Tao Meng, Xiao-Bing Du, Shao-Qing Lei, Zhong-Yuan Xia
Long non-coding (lncRNA) MALAT1 can be increased by hypoxia or ischemic limbs. Also, downregulation of MALAT1 contributes to reduction of cardiomyocyte apoptosis. However, the functional involvement of MALAT1 in myocardial ischemia-reperfusion (I/R) injury has not been defined. This study investigated the functional involvement of lncRNA-MALAT1 in cardioprotective effects of fentanyl. HL-1, a cardiac muscle cell line from the AT-1 mouse atrial cardiomyocyte tumor lineage was pre-treated with fentanyl and generated cell model of hypoxia-reoxygenation (H/R)...
January 2017: Cell Biology International
https://www.readbyqxmd.com/read/27861891/opa1-haploinsufficiency-induces-a-bnip3-dependent-decrease-in-mitophagy-in-neurons-relevance-to-dominant-optic-atrophy
#15
Manon F Moulis, Aurélie M Millet, Marlène Daloyau, Marie-Christine Miquel, Brice Ronsin, Bernd Wissinger, Laetitia Arnauné-Pelloquin, Pascale Belenguer
Dominant optic atrophy (DOA) is because of mutations in the mitochondrial protein OPA1. The disease principally affects retinal ganglion cells, whose axons degenerate leading to vision impairments, and sometimes other neuronal phenotypes. The exact mechanisms underlying DOA pathogenesis are not known. We previously demonstrated that the main role of OPA1, as a mitochondrial fusogenic and anti-apoptotic protein, are inhibited by interaction with the stress inducible pro-apoptotic BNIP3 protein. Because BNIP3 was recently reported to participate in autophagy and mitophagy, we tested the involvement of these processes in DOA pathogenesis...
November 10, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27858285/the-role-of-hypoxia-inducible-factor-1-in-mild-cognitive-impairment
#16
REVIEW
Osigbemhe Iyalomhe, Sabina Swierczek, Ngozi Enwerem, Yuanxiu Chen, Monica O Adedeji, Joanne Allard, Oyonumo Ntekim, Sheree Johnson, Kakra Hughes, Philip Kurian, Thomas O Obisesan
Neuroinflammation and reactive oxygen species are thought to mediate the pathogenesis of Alzheimer's disease (AD), suggesting that mild cognitive impairment (MCI), a prodromal stage of AD, may be driven by similar insults. Several studies document that hypoxia-inducible factor 1 (HIF-1) is neuroprotective in the setting of neuronal insults, since this transcription factor drives the expression of critical genes that diminish neuronal cell death. HIF-1 facilitates glycolysis and glucose metabolism, thus helping to generate reductive equivalents of NADH/NADPH that counter oxidative stress...
November 17, 2016: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/27837193/intact-initiation-of-autophagy-and-mitochondrial-fission-by-acute-exercise-in-skeletal-muscle-of-patients-with-type%C3%A2-2-diabetes
#17
Rikke Kruse, Andreas J T Pedersen, Jonas M Kristensen, Stine J Petersson, Jørgen F P Wojtaszewski, Kurt Højlund
Type 2 diabetes (T2D) is characterized by insulin resistance, mitochondrial dysregulation and, in some studies, exercise resistance in skeletal muscle. Regulation of autophagy and mitochondrial dynamics during exercise and recovery is important for skeletal muscle homoeostasis, and these responses may be altered in T2D. We examined the effect of acute exercise on markers of autophagy and mitochondrial fusion and fission in skeletal muscle biopsies from patients with T2D (n=13) and weight-matched controls (n=14) before, immediately after and 3 h after an acute bout of exercise...
January 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27807188/autophagy-induction-results-in-enhanced-anoikis-resistance-in-models-of-peritoneal-disease
#18
James L Chen, Jason David, Douglas Cook-Spaeth, Sydney Casey, David Cohen, Karuppaiyah Selvendiran, Tanios Bekaii-Saab, John Hays
: Peritoneal carcinomatosis and peritoneal sarcomatosis (PC/PS) is a potential complication of nearly all solid tumors and results in profoundly increased morbidity and mortality. Despite the ubiquity of PC/PS, there are no clinically relevant targeted therapies for either its treatment or prevention. To identify potential therapies, we developed in vitro models of PC/PS using tumor cell lines and patient-derived spheroids (PDS) that recapitulate anoikis resistance and spheroid proliferation across multiple cancer types...
November 2, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27800505/fifteen-days-of-3-200-m-simulated-hypoxia-marginally-regulates-markers-for-protein-synthesis-and-degradation-in-human-skeletal-muscle
#19
Gommaar D'Hulst, Alessandra Ferri, Damien Naslain, Luc Bertrand, Sandrine Horman, Marc Francaux, David J Bishop, Louise Deldicque
Chronic hypoxia leads to muscle atrophy. The molecular mechanisms responsible for this phenomenon are not well defined in vivo. We sought to determine how chronic hypoxia regulates molecular markers of protein synthesis and degradation in human skeletal muscle and whether these regulations were related to the regulation of the hypoxia-inducible factor (HIF) pathway. Eight young male subjects lived in a normobaric hypoxic hotel (FiO2 14.1%, 3,200 m) for 15 days in well-controlled conditions for nutrition and physical activity...
2016: Hypoxia
https://www.readbyqxmd.com/read/27787518/glioblastoma-hypoxia-and-autophagy-a-survival-prone-m%C3%A3-nage-%C3%A3-trois
#20
REVIEW
Soha Jawhari, Marie-Hélène Ratinaud, Mireille Verdier
Glioblastoma multiforme is the most common and the most aggressive primary brain tumor. It is characterized by a high degree of hypoxia and also by a remarkable resistance to therapy because of its adaptation capabilities that include autophagy. This degradation process allows the recycling of cellular components, leading to the formation of metabolic precursors and production of adenosine triphosphate. Hypoxia can induce autophagy through the activation of several autophagy-related proteins such as BNIP3, AMPK, REDD1, PML, and the unfolded protein response-related transcription factors ATF4 and CHOP...
October 27, 2016: Cell Death & Disease
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