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https://www.readbyqxmd.com/read/28079158/aryl-hydrocarbon-receptor-ahr-dependent-regulation-of-pulmonary-mirna-by-chronic-cigarette-smoke-exposure
#1
Sarah Rogers, Angela Rico de Souza, Michela Zago, Matthew Iu, Necola Guerrina, Alvin Gomez, Jason Matthews, Carolyn J Baglole
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor historically known for its toxic responses to man-made pollutants such as dioxin. More recently, the AhR has emerged as a suppressor of inflammation, oxidative stress and apoptosis from cigarette smoke by mechanisms that may involve the regulation of microRNA. However, little is known about the AhR regulation of miRNA expression in the lung in response to inhaled toxicants. Therefore, we exposed Ahr(-/-) and Ahr(+/-) mice to cigarette smoke for 4 weeks and evaluated lung miRNA expression by PCR array...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28078537/sirt2-mediated-foxo3a-deacetylation-drives-its-nuclear-translocation-triggering-fasl-induced-cell-apoptosis-during-renal-ischemia-reperfusion
#2
Yan Wang, Yu Mu, Xiaorui Zhou, Huaixue Ji, Xing Gao, Wen Wen Cai, Qiuhua Guan, Tie Xu
We have found that Fas/FasL-mediated "extrinsic" pathway promoted cell apoptosis induced by renal ischemic injury. This study is to elucidate the upstream mechanism regulating FasL-induced extrinsic pathway during renal ischemia/reperfusion. Results demonstrated that when SIRT2 was activated by renal ischemia/reperfusion, activated SIRT2 could bind to and deacetylate FOXO3a, promoting FOXO3a nuclear translocation which resulted in an increase of nuclear FOXO3a along with FasL expression and activation of caspase8 and caspase3, triggering cell apoptosis during renal ischemia/reperfusion...
January 11, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28054503/inhibition-of-telomerase-using-bibr1532-enhances-doxorubicin-induced-apoptosis-in-pre-b-acute-lymphoblastic-leukemia-cells
#3
Davood Bashash, Mohadeseh Zareii, Ava Safaroghli-Azar, Mir Davood Omrani, Seyed H Ghaffari
OBJECTIVES: Interest into targeting telomerase in cancer has increased by the recent disclosure that elevated telomerase activity is associated with disease recurrence and poor outcome in cancers. In addition, cellular acquisition of unlimited replicative potential, which is closely related to the maintenance of telomeres mostly via the reactivation of telomerase, has been shown to confer loss of sensitivity to a wide range of anti-neoplastic agents. METHODS: To evaluate whether telomerase inhibition using non-nucleosidic inhibitor of telomerase BIBR1532 could enhance cytotoxic effect of doxorubicin in acute lymphoblastic leukemia, Nalm-6 pre-B ALL cells were subjected to combination treatment and subsequent cell viability, growth kinetics, caspase-3 activity, and transcriptional alteration of p73, p21, FOXO3a, c-Myc, hTERT, and other apoptosis-related target genes were investigated...
January 5, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28046000/cytosolic-extract-of-human-adipose-stem-cells-reverses-the-amyloid-beta-induced-mitochondrial-apoptosis-via-p53-foxo3a-pathway
#4
Tian Liu, Mijung Lee, Jae-Jun Ban, Wooseok Im, Inhee Mook-Jung, Manho Kim
Human adipose stem cells (hASC) have therapeutic potential for the treatment of neurodegenerative disorders. Mitochondrial dysfunction is frequently observed in most neurodegenerative disorders, including Alzheimer's disease. We explored the therapeutic potential of hASC cytosolic extracts to attenuate neuronal death induced by mitochondrial dysfunction in an Alzheimer's disease (AD) in vitro models. Amyloid beta (Aβ) was used to induce cytotoxity in an immortal hippocampal cell line (HT22) and neuronal stem cells from the brain of TG2576 transgenic mice were also used to test the protective role of hASC cytosolic extracts...
2017: PloS One
https://www.readbyqxmd.com/read/28036393/soluble-egg-antigens-of-schistosoma-japonicum-induce-senescence-of-activated-hepatic-stellate-cells-by-activation-of-the-foxo3a-skp2-p27-pathway
#5
Yinong Duan, Jing Pan, Jinling Chen, Dandan Zhu, Jianxin Wang, Xiaolei Sun, Liuting Chen, Liting Wu
BACKGROUND: Liver fibrosis was viewed as a reversible process. The activation of hepatic stellate cells (HSCs) is a key event in the process of liver fibrosis. The induction of senescence of HSCs would accelerate the clearance of the activated HSCs. Previously, we demonstrated that soluble egg antigens (SEA) of Schistosoma japonicum promoted the senescence of HSCs via STAT3/P53/P21 pathway. In this paper, our study was aimed to explore whether there are other signaling pathways in the process of SEA-induced HSCs aging and the underlying effect of SKP2/P27 signal on senescent HSCs...
December 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28036259/subcellular-localization-of-foxo3a-as-a-potential-biomarker-of-response-to-combined-treatment-with-inhibitors-of-pi3k-and-autophagy-in-pik3ca-mutant-cancer-cells
#6
Hyun-Jung Kim, Soo Yoon Lee, Chan Young Kim, Yun Hwan Kim, Woong Ju, Seung Chloe Kim
Autophagy is the process of lysosome-mediated degradation and recycling that functions as an adaptive survival mechanism during anti-cancer therapy. Aberrant activation of the phosphoinositide-3-kinase (PI3K) pathway frequently occurs in solid tumors, including cervical cancer. However, single-agent PI3K inhibitors show modest anti-tumor efficacy in clinics. To see whether autophagy inhibition improves the efficacy of PI3K inhibitor in PIK3CA-mutant cancer cells, cells were treated with BKM120, a pan-PI3K inhibitor, and the autophagy inhibitor hydroxychloroquine (HCQ)...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28031321/inflammatory-hypoxia-induces-syndecan-2-expression-through-il-1%C3%AE-mediated-foxo3a-activation-in-colonic-epithelia
#7
Sojoong Choi, Heesung Chung, Heejeong Hong, So Yeon Kim, Seong-Eun Kim, Ju-Young Seoh, Chang Mo Moon, Eun Gyeong Yang, Eok-Soo Oh
Chronic inflammation is known to be a key causative factor in tumor progression, but we do not yet fully understand the molecular mechanism through which inflammation leads to cancer. Here, we report that the dextran sulfate sodium (DSS)-induced mouse model of chronic colitis is associated with increases in the serum level of IL-1β and the colonic epithelial expression of the cell-surface heparan sulfate proteoglycan, syndecan-2. We further show that IL-1β stimulated the transcription of syndecan-2 via NF-κB-dependent FOXO3a activation in normal colonic epithelial cells (CCD841CoN cells) and early-stage colon cancer cells (HT29 cells)...
December 28, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28006785/mir-155-is-involved-in-renal-ischemia-reperfusion-injury-via-direct-targeting-of-foxo3a-and-regulating-renal-tubular-cell-pyroptosis
#8
Haoyu Wu, Tao Huang, Liang Ying, Conghui Han, Dawei Li, Yao Xu, Ming Zhang, Shan Mou, Zhen Dong
BACKGROUND/AIMS: Ischemia/reperfusion injury (IRI) plays a crucial role in renal transplantation and can cause renal failure associated with pyroptosis, a pro-inflammatory-induced programmed cell death. Small endogenous non-coding RNAs have been shown to be involved in renal ischemia/reperfusion injury. This study was performed to investigate which miRNAs regulate pyroptosis in response to renal ischemia/reperfusion injury and determine the mechanism underlying this regulation. METHODS: An in vivo rat model of renal IRI was established, and the serum and kidneys were harvested 24 h after reperfusion to assess renal function and histological changes...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28006775/fgf-2-transcriptionally-down-regulates-the-expression-of-bnip3l-via-pi3k-akt-foxo3a-signaling-and-inhibits-necrosis-and-mitochondrial-dysfunction-induced-by-high-concentrations-of-hydrogen-peroxide-in-h9c2-cells
#9
Qian Chen, Xiaosong Chen, Conghui Han, Ying Wang, Tao Huang, Yingdong Du, Zhen Dong
BACKGROUND/AIMS: Cardiovascular disease is a growing major global public health problem. Necrosis is one of the main forms of cardiomyocyte death in heart disease. Oxidative stress is regarded as one of the key regulators of cardiac necrosis, which eventually leads to cardiovascular disease. Many pharmacological and in vitro studies have suggested that FGF-2 can act directly on cardiomyocytes to maintain the integrity and function of the myocardium and prevent damage during oxidative stress...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27998725/cgmp-signaling-increases-antioxidant-gene-expression-by-activating-forkhead-box-o-3a-in-the-colon-epithelium
#10
Rui Wang, Bianca Islam, Allison Bridges, Sarah Sharman, Muhan Hu, Yali Hou, Payaningal R Somanath, Laine Venable, Nagendra Singh, Sangmi Kim, Subbaramiah Sridhar, Franz Hofmann, Darren D Browning
Signaling through cGMP has therapeutic potential in the colon, where it has been implicated in the suppression of colitis and colon cancer. In this study, we tested the ability of cGMP and type 2 cGMP-dependent protein kinase (PKG2) to activate forkhead box O (FoxO) in colon cancer cells and in the colon epithelium of mice. We show that activation of PKG2 in colon cancer cells inhibited cell proliferation, inhibited AKT, and activated FoxO. Treatment of colon explants with 8Br-cGMP also activated FoxO target gene expression at both RNA and protein levels, and reduced epithelial reduction-oxidation (redox) stress...
December 17, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27976455/evaluation-of-the-p-akt-p-jnk-and-foxo3a-function-in-the-oral-epithelial-dysplasia-malignance
#11
Filipe Nobre Chaves, Thâmara Manoela Marinho Bezerra, Paulo Goberlânio de Barros Silva, Francisco Artur Forte Oliveira, Fabrício Bitu Sousa, Fábio Wildson Gurgel Costa, Ana Paula Negreiros Nunes Alves, Karuza Maria Alves Pereira
OBJECTIVES: To evaluate the expression of p-AKT, p-JNK, FoxO3a and KI-67 in samples of Oral Squamous Cell Carcinoma (OSCC) and Oral Epithelial Dysplasias (OEDs) to understand their possible involvement in the malignant transformation process of oral lesions. MATERIALS AND METHODS: Tissue samples of 20 cases of OSCCs, 20 OEDs and normal oral mucosa were subjected to immunohistochemistry reactions for anti-p-Akt, anti-p-JNK, anti-FoxO3a and anti-Ki-67 antibodies. It was analyzed quantitative (number of immunostained cells) and qualitative (immunostaining intensity) parameters in different cell immunostaining sublocations...
December 14, 2016: Oral Diseases
https://www.readbyqxmd.com/read/27936162/discovery-of-a-novel-isothiazolonaphthoquinone-based-small-molecule-activator-of-foxo-nuclear-cytoplasmic-shuttling
#12
Bastien Cautain, Francisco Castillo, Loana Musso, Bibiana I Ferreira, Nuria de Pedro, Lorena Rodriguez Quesada, Susana Machado, Francisca Vicente, Sabrina Dallavalle, Wolfgang Link
FOXO factors are tumour suppressor proteins commonly inactivated in human tumours by posttranslational modifications. Furthermore, genetic variation within the FOXO3a gene is consistently associated with human longevity. Therefore, the pharmacological activation of FOXO proteins is considered as an attractive therapeutic approach to treat cancer and age-related diseases. In order to identify agents capable of activating FOXOs, we tested a collection of small chemical compounds using image-based high content screening technology...
2016: PloS One
https://www.readbyqxmd.com/read/27924057/pazopanib-a-novel-multi-kinase-inhibitor-shows-potent-antitumor-activity-in-colon-cancer-through-puma-mediated-apoptosis
#13
Lingling Zhang, Huanan Wang, Wei Li, Juchang Zhong, Rongcheng Yu, Xinfeng Huang, Honghui Wang, Zhikai Tan, Jiangang Wang, Yingjie Zhang
Colon cancer is still the third most common cancer which has a high mortality but low five-year survival rate. Novel tyrosine kinase inhibitors (TKI) such as pazopanib become effective antineoplastic agents that show promising clinical activity in a variety of carcinoma, including colon cancer. However, the precise underlying mechanism against tumor is unclear. Here, we demonstrated that pazopanib promoted colon cancer cell apoptosis through inducing PUMA expression. Pazopanib induced p53-independent PUMA activation by inhibiting PI3K/Akt signaling pathway, thereby activating Foxo3a, which subsequently bound to the promoter of PUMA to activate its transcription...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27922594/cacna1c-in-the-prefrontal-cortex-regulates-depression-related-behaviors-via-redd1
#14
Zeeba D Kabir, Anni S Lee, Caitlin E Burgdorf, Delaney Fischer, Aditi M Rajadhyaksha, Ethan Mok, Bryant Rizzo, Richard C Rice, Kamalpreet Singh, Kristie T Ota, Danielle M Gerhard, Kathryn C Schierberl, Michael Glass, Ronald S Duman, Anjali M Rajadhyaksha
The CACNA1C gene that encodes the L-type Ca(2+) channel (LTCC) Cav1.2 subunit has emerged as a candidate risk gene for multiple neuropsychiatric disorders including bipolar disorder, major depressive disorder and schizophrenia, all marked with depression-related symptoms. Although cacna1c heterozygous (HET) mice have been previously reported to exhibit an antidepressant-like phenotype, the molecular and circuit-level dysfunction remains unknown. Here we report that viral vector-mediated deletion of cacna1c in the adult prefrontal cortex (PFC) of mice recapitulates the antidepressant-like effect observed in cacna1c HET mice using the sucrose preference test (SPT), the forced swim test (FST), and the tail suspension test (TST)...
December 6, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27919684/neuroprotective-effects-of-mir-27a-against-traumatic-brain-injury-via-suppressing-foxo3a-mediated-neuronal-autophagy
#15
Liqian Sun, Manman Zhao, Yan Wang, Aihua Liu, Ming Lv, Youxiang Li, Xinjian Yang, Zhongxue Wu
MicroRNA-27a (miR-27a) has been reported to be a brain-specific miRNA and aberrantly expressed in the brain suffered from traumatic brain injury (TBI). The present study is designed to investigate the potential role and molecular mechanism of miR-27a in the pathogenesis of TBI. The level of miR-27a in brain was manipulated by intracerebroventricular injection of lentiviral-encoding miR-27a before TBI induction. Real-time PCR was used to detected miR-27a and Forkhead box O3a (FoxO3a) levels in the hippocampus...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27903254/mir-96-mir-145-and-mir-9-expression-increases-and-igf-1r-and-foxo1-expression-decreases-in-peripheral-blood-mononuclear-cells-of-aging-humans
#16
Monika Budzinska, Magdalena Owczarz, Eliza Pawlik-Pachucka, Malgorzata Roszkowska-Gancarz, Przemyslaw Slusarczyk, Monika Puzianowska-Kuznicka
BACKGROUND: In mammals, the IGF-1 pathway affects the phenotype of aging. Since the function of the immune system is modulated by IGF-1, it is plausible that immunosenescence might in part result from altered control by this pathway. We therefore examined whether the expression of IGF-1R, FOXO1, and FOXO3a in peripheral blood mononuclear cells (PBMC) changes with age and if this might be due to changes in the expression of select miRNAs. METHODS: The expression of IGF-1R, FOXO1, FOXO3a, as well as of miR-9, miR-96, miR-99a, miR-132, miR-145, and miR-182 was examined in PBMC of young (27...
November 30, 2016: BMC Geriatrics
https://www.readbyqxmd.com/read/27900085/id1-upregulation-and-foxo3a-downregulation-by-epstein-barr-virus-encoded-lmp1-in-hodgkin-s-lymphoma
#17
Jun-Ichiro Ikeda, Naoki Wada, Satoshi Nojima, Shinichiro Tahara, Yoko Tsuruta, Kaori Oya, Eiichi Morii
Cancer-initiating cells (CICs) are specialized cells that have the ability to self-renew and are multipotent. We recently demonstrated that Forkhead box O3a (FoxO3a)-expressing cells exhibited a CIC-like potential in Hodgkin's lymphoma (HL). A proportion of HL patients are infected with Epstein-Barr virus (EBV). EBV-encoded latent membrane protein (LMP) 1 downregulates FoxO3a, suggesting that FoxO3a expression may be abolished in EBV-positive HL. Inhibitors of DNA-binding (ID) proteins are highly conserved transcription factors mediating stem cell functions...
November 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/27898096/on-a-fox-hunt-functions-of-fox-transcriptional-regulators-in-bladder-cancer
#18
REVIEW
Hironobu Yamashita, Vasty Osei Amponsa, Joshua I Warrick, Zongyu Zheng, Peter E Clark, Jay D Raman, Xue-Ru Wu, Cathy Mendelsohn, David J DeGraff
Genomic and transcriptional studies have identified discrete molecular subtypes of bladder cancer. These observations could be the starting point to identify new treatments. Several members of the forkhead box (FOX) superfamily of transcription factors have been found to be differentially expressed in the different bladder cancer subtypes. In addition, the FOXA protein family are key regulators of embryonic bladder development and patterning. Both experimental and clinical data support a role for FOXA1 and FOXA2 in urothelial carcinoma...
November 29, 2016: Nature Reviews. Urology
https://www.readbyqxmd.com/read/27881235/elucidating-the-role-of-the-foxo3a-transcription-factor-in-the-igf-1-induced-migration-and-invasion-of-uveal-melanoma-cancer-cells
#19
Fengxia Yan, Rifang Liao, Mohd Farhan, Tinghuai Wang, Jiashu Chen, Zhong Wang, Peter J Little, Wenhua Zheng
Uveal melanoma (UM) is the most common primary intraocular malignant tumor of adults. It has high mortality rate due to liver metastasis. However, the epidemiology and pathogenesis of liver metastasis in UM are not elucidated and there is no effective therapy available for preventing the development of this disease. IGF-1 is a growth factor involved in cell proliferation, malignant transformation and inhibition of apoptosis. In previous report, IGF-1 receptor was found to be highly expressed in UM and this was related to tumor prognosis...
December 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27875304/rapid-renal-regulation-of-peroxisome-proliferator-activated-receptor-%C3%AE-coactivator-1%C3%AE-by-extracellular-signal-regulated-kinase-1-2-in-physiological-and-pathological-conditions
#20
Justin B Collier, Ryan M Whitaker, Scott T Eblen, Rick G Schnellmann
Previous studies have shown that extracellular signal-regulated kinase 1/2 (ERK1/2) directly inhibits mitochondrial function during cellular injury. We evaluated the role of ERK1/2 on the expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) gene, a master regulator of mitochondrial function. The potent and specific MEK1/2 inhibitor trametinib rapidly blocked ERK1/2 phosphorylation, decreased cytosolic and nuclear FOXO3a/1 phosphorylation, and increased PGC-1α gene expression and its downstream mitochondrial biogenesis (MB) targets under physiological conditions in the kidney cortex and in primary renal cell cultures...
December 23, 2016: Journal of Biological Chemistry
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