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https://www.readbyqxmd.com/read/28537876/activation-of-perk-branch-of-er-stress-mediates-homocysteine-induced-bkca%C3%A2-channel-dysfunction-in-coronary-artery-via-foxo3a-dependent-regulation-of-atrogin-1
#1
Wen-Tao Sun, Xiang-Chong Wang, Shiu-Kwong Mak, Guo-Wei He, Xiao-Cheng Liu, Malcolm John Underwood, Qin Yang
The molecular mechanism of endoplasmic reticulum (ER) stress in vascular pathophysiology remains inadequately understood. We studied the role of ER stress in homocysteine-induced impairment of coronary dilator function, with uncovering the molecular basis of the effect of ER stress on smooth muscle large-conductance Ca2+-activated K+ (BKCa) channels. The vasodilatory function of BKCa channels was studied in a myograph using endothelium-denuded porcine small coronary arteries. Primary cultured porcine coronary artery smooth muscle cells were used for mRNA and protein measurements and current recording of BKCa channels...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28530705/ccn5-wisp-2-restores-er-%C3%A2-in-normal-and-neoplastic-breast-cells-and-sensitizes-triple-negative-breast-cancer-cells-to-tamoxifen
#2
S Sarkar, A Ghosh, S Banerjee, G Maity, A Das, M A Larson, V Gupta, I Haque, O Tawfik, S K Banerjee
CCN5/WISP-2 is an anti-invasive molecule and prevents breast cancer (BC) progression. However, it is not well understood how CCN5 prevents invasive phenotypes of BC cells. CCN5 protein expression is detected in estrogen receptor-α (ER-α) -positive normal breast epithelial cells as well as BC cells, which are weakly invasive and rarely metastasize depending on the functional status of ER-α. A unique molecular relation between CCN5 and ER-α has been established as the components of the same signaling pathway that coordinate some essential signals associated with the proliferation as well as delaying the disease progression from a non-invasive to invasive phenotypes...
May 22, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28529032/synergistic-cytotoxicity-of-lenalidomide-and-dexamethasone-in-mantle-cell-lymphoma-via-cereblon-dependent-targeting-of-the-il-6-stat3-pi3k-axis
#3
Jiexian Ma, Kefei Wu, Weiya Bai, Xiaoxian Cui, Yan Chen, Youhua Xie, Yanhui Xie
At our center, relapsed mantle cell lymphoma (MCL) can be treated with maintenance therapy composed of consecutive low-dose lenalidomide and short-term, high-dose dexamethasone (LD regimen), which achieves good responses (longer overall survival and progression-free survival) and low toxicity. Cereblon is probably targeted by both lenalidomide and dexamethasone, which leads to synergistic cytotoxicity in MCL by inhibiting the interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3), phosphatidylinositol 3-kinase (PI3K)/AKT and AKT2/Forkhead box O3 (FOXO3A)/BCL2-like 11 (BIM) pathways...
May 10, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28528294/isoliquiritigenin-reduces-oxidative-damage-and-alleviates-mitochondrial-impairment-by-sirt1-activation-in-experimental-diabetic-neuropathy
#4
Veera Ganesh Yerra, Anil Kumar Kalvala, Ashutosh Kumar
Sirtuin (SIRT1) inactivation underlies the pathogenesis of insulin resistance and hyperglycaemia-associated vascular complications, but its role in diabetic neuropathy (DN) has not been yet explored. We have evaluated hyperglycaemia-induced alteration of SIRT1 signalling and the effect of isoliquiritigenin (ILQ) on SIRT1-directed AMP kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) signalling in peripheral nerves of streptozotocin (STZ) (55 mg/kg, ip)-induced diabetic rats and in high glucose (30 mM)-exposed neuro2a (N2A) cells...
May 11, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28528184/synergistic-antitumor-effect-of-nvp-bez235-and-cape-on-mda-mb-231-breast-cancer-cells
#5
Samira Torki, Amin Soltani, Hedayatollah Shirzad, Nafiseh Esmaeil, Mahdi Ghatrehsamani
Triple negative breast cancer (TNBC) is the most lethal and aggressive kind of breast cancer. Studies with TNBC cells suggest that tumor environmental cytokines such as Transforming Growth Factor β1 (TGF-β1) have important roles in tumors fate. In the present study, we aimed to investigate, the effect of phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway dual inhibitor, NVP-BEZ235 and Caffeic acid phenyl ester (CAPE) on TNBC cell line (MDA-MB-231), stimulated with TGF-β1 for 14days in vitro...
May 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28526626/longevity-and-healthy-ageing-genes-foxo3a-and-sirt3-serum-protein-marker-and-new-road-map-to-burst-oxidative-stress-by-withania-somnifera
#6
Rashmita Pradhan, Rahul Kumar, Shashank Shekhar, Nitish Rai, Akash Ambashtha, Joyita Banerjee, Mona Pathak, S N Dwivedi, Sharmistha Dey, Aparajit B Dey
BACKGROUND: Ageing process is characterized by a decline in function; different age related diseases and excessive age associated mortality. There has always been a quest for easily accessible biomarkers to monitor and identify the development of age-associated stress for providing new anti-ageing strategies. Forkhead box protein O3A (FOXO3A) and Sirtuin3 (SIRT3) are such potential markers which plays important role in a wide variety of cellular mechanisms and has been proposed to be an ideal candidate to study longevity and are potential candidate for healthy ageing by oxidative burst...
May 16, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28521392/phosphorylation-and-acetylation-modifications-of-foxo3a-independently-or-synergistically
#7
Xianwang Wang, Shujuan Hu, Lei Liu
Forkhead box class O 3a (FOXO3a) is a transcription factor that has emerged as being a tumor suppressor and longevity factor. The precise regulation of FOXO3a transactivation of target genes is achieved via post-translational modifications (PTMs) and specific protein-protein interactions. The multiple types of PTMs that FOXO3a undergoes, including phosphorylation, acetylation, methylation and ubiquitination, serve important roles in directing its subcellular localization and transcription activity, which are central to the integration of insulin/growth factor signaling and oxidative/nutrient stress signaling...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28514752/%C3%AE-msh-inhibits-adipose-inflammation-via-reducing-foxos-transcription-and-blocking-akt-jnk-pathway-in-mice
#8
Guannv Liu, Meihang Li, Muhammad Saeed, Yatao Xu, Qian Ren, Chao Sun
Alpha melanocyte stimulating hormone (αMSH) abates inflammation in multiple tissues, while Forkhead box proteins O (FoxOs) stimulate inflammatory cascade. However, the relationship between αMSH and FoxOs in adipose inflammation remains unclear. In this study, we used LPS-induced inflammation model, attempted to interpret the function of αMSH in inflammation and the interactions with FoxOs. Results indicated that upon inflammatory situation, the secretion of αMSH and the expression of its receptor MC5R were greatly decreased, but FoxOs expressions were elevated...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28506746/the-nad-dependent-deacetylase-bifidobacterium-longum-sir2-in-response-to-oxidative-stress-by-deacetylating-foxo3a-and-sigh-%C3%AF-h-in-bifidobacterium-longum-and-hek293t-cells-respectively
#9
Qing Guo, Shiyu Li, Yajie Xie, Qian Zhang, Mengge Liu, Zhenrui Xu, Hanxiao Sun, Yan Yang
Silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent protein/histone deacetylation. The mammalian sirtuin family SIRT1, SIRT2, SIRT3 and SIRT6 can regulate oxidative stress. The probiotics (Bifidobacterium longum(B.longum) and Lactobacillus acidophilus(L. acidophilus)) have Sir2 gene family and have antioxidant activity in human body. it remains unknown whether probiotics Sir2 has a direct role in regulating oxidative stress. To this end, we knockout BL-sir2(sir2 B. longum) and LA-sir2(sir2 L...
May 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28503736/hydrogen-sulfide-pretreatment-improves-mitochondrial-function-in-myocardial-hypertrophy-via-a-sirt3-dependent-manner
#10
Guoliang Meng, Jieqiong Liu, Shangmin Liu, Qiuyi Song, Lulu Liu, Liping Xie, Yi Han, Yong Ji
BACKGROUND AND PURPOSE Hydrogen sulfide (H2 S) is a gaseous signal molecule with anti-oxidative ability. Sirtuin 3 (SIRT3) is closely associated with mitochondrial function and oxidative stress. The study was to investigate whether and how H2 S improved myocardial hypertrophy via a SIRT3-dependent manner. EXPERIMENTAL APPROACH Neonatal rat cardiomyocytes were pre-treated with NaHS (50 μM) for 4 h followed by angiotensin II (Ang II, 100 nM) for 24 h. SIRT3 was silenced with siRNA technology. SIRT 3 promoter activity and expression, cell surface, hypertrophic gene mRNA expression, mitochondrial oxygen consumption rate and membrane potential were measured...
May 15, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28502921/umbilical-cord-mscs-reverse-d-galactose-induced-hepatic-mitochondrial-dysfunction-via-activation-of-nrf2-ho-1-pathway
#11
Weihong Yan, Dong Li, Tong Chen, Guiying Tian, Panpan Zhou, Xiuli Ju
Mitochondria are the central hubs for cellular bioenergetics and are crucial to cell survival. It is well accepted that compromised mitochondrial function is linked with hepatocytes injury and contribute to progression of liver diseases. Despite the therapeutic potential of mesenchymal stem cells (MSCs) transplantation on hepatic disorders have been extensively investigated, the effects of MSCs on mitochondrial function in liver injury models remain unknown. Here we investigated the effects of treatment with umbilical cord (UC) MSC in a rat model of D-Gal induced liver injury, characterized by organ damage, oxidative stress and mitochondrial dysfunction...
May 13, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28499802/ampk-activates-foxo3a-and-promotes-neuronal-apoptosis-in-the-developing-rat-brain-during-the-early-phase-after-hypoxia-ischemia
#12
Deyuan Li, Lili Luo, Min Xu, Jinlin Wu, Lina Chen, Jinhui Li, Zhongqiang Liu, Guoyan Lu, Yang Wang, Lina Qiao
AMP-activated protein kinase (AMPK) is a key metabolic and stress sensor/effector. Few investigations have been performed to study the role of AMPK in developing rat brain with hypoxia-ischemia (HI). Forkhead transcriptional factor (FOXO3a) has been revealed to be a critical effector of AMPK-mediated celluar apoptosis. However, it is not clear whether AMPK/FOXO3a pathway is involved in neuronal apoptosis in the developing rat brain after HI. In this study, we generated hypoxia-ischemia brain damage (HIBD) model using postnatal day 7 rats...
May 10, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28494348/withaferin-a-inhibits-prostate-carcinogenesis-in-a-pten-deficient-mouse-model-of-prostate-cancer
#13
Jim Moselhy, Suman Suman, Mohammed Alghamdi, Balaji Chandarasekharan, Trinath P Das, Alatassi Houda, Murali Ankem, Chendil Damodaran
We recently demonstrated that AKT activation plays a role in prostate cancer progression and inhibits the pro-apoptotic function of FOXO3a and Par-4. AKT inhibition and Par-4 induction suppressed prostate cancer progression in preclinical models. Here, we investigate the chemopreventive effect of the phytonutrient Withaferin A (WA) on AKT-driven prostate tumorigenesis in a Pten conditional knockout (Pten-KO) mouse model of prostate cancer. Oral WA treatment was carried out at two different doses (3 and 5 mg/kg) and compared to vehicle over 45 weeks...
May 7, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28468801/%C3%AE-np63%C3%AE-is-a-common-inhibitory-target-in-oncogenic-pi3k-ras-her2-induced-cell-motility-and-tumor-metastasis
#14
Linshan Hu, Shan Liang, Hu Chen, Tao Lv, Junfeng Wu, Deshi Chen, Min Wu, Shengnan Sun, Haibo Zhang, Han You, Hongbin Ji, Yujun Zhang, Johann Bergholz, Zhi-Xiong Jim Xiao
Activation of phosphatidylinositol 3 kinase (PI3K), Ras, and Her2 signaling plays a critical role in cancer development. Hotspot constitutive activating mutations in oncogenes, such as PIK3CA encoding the p110α catalytic subunit or RAS, as well as overexpression of Her2, are frequently found in human tumors and cancers. It has been well established that activation of these oncogenes profoundly promotes tumor metastasis, whereas decreased expression of ΔNp63α, the major protein isoform of the p53-related p63 expressed in epithelial cells, has been associated with cancer metastasis...
May 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28455433/akt2-regulates-pulmonary-inflammation-and-fibrosis-via-modulating-macrophage-activation
#15
Yunjuan Nie, Lei Sun, Yaxian Wu, Yaoyao Yang, Jun Wang, Huiqiong He, Yudong Hu, Yanhua Chang, Qing Liang, Jianwei Zhu, Richard D Ye, John W Christman, Feng Qian
Idiopathic pulmonary fibrosis (IPF) is a highly lethal pathological process that is characterized by inflammation, fibroblast accumulation, and excessive collagen deposition. Although AKT2-mediated signaling pathways modulate inflammatory responses, their role in IPF has not been defined. We report that AKT2 deficiency (Akt2(-/-)) protected against bleomycin-induced pulmonary fibrosis and inflammation. Adoptive transfer of wild-type macrophages or administration of IL-13 to Akt2(-/-) mice could restore pulmonary fibrosis...
April 28, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28445931/high-glucose-induces-apoptosis-via-upregulation-of-bim-expression-in-proximal-tubule-epithelial-cells
#16
Xiao-Qian Zhang, Jian-Jun Dong, Tian Cai, Xue Shen, Xiao-Jun Zhou, Lin Liao
Diabetic nephropathy is the primary cause of end-stage renal disease. Apoptosis of tubule epithelial cells is a major feature of diabetic nephropathy. The mechanisms of high glucose (HG) induced apoptosis are not fully understood. Here we demonstrated that, HG induced apoptosis via upregulating the expression of proapoptotic Bcl-2 homology domain 3 (BH3)-only protein Bim protein, but not bring a significant change in the baseline level of autophagy in HK2 cells. The increase of Bim expression was caused by the ugregulation of transcription factors, FOXO1 and FOXO3a...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28440481/the-specific-killing-effect-of-matrine-on-castration-resistant-prostate-cancer-cells-by-targeting-the-akt-foxo3a-signaling-pathway
#17
Shoumin Bai, Ting Chen, Xiaoli Yu, Ming Luo, Xianju Chen, Chunhao Lin, Yiming Lai, Hai Huang
Matrine, a Sophora alkaloid, exhibits antiproliferative and anti-carcinogenic activities through several mechanisms. In a previous study, we found that matrine could effectively inhibit the proliferation of castration-resistant prostate cancer (CRPC). In the present study, the effect of matrine and LY294002 on the expression of the Akt/FoxO3a signaling pathway was examined by western blot analyses and RT-PCR. We discovered that matrine significantly inhibited the proliferation of both prostate cancer cell line PC-3 and prostate epithelial cell line RWPE1, induced apoptosis and induced cell cycle arrest...
May 2017: Oncology Reports
https://www.readbyqxmd.com/read/28436000/foxo3a-suppression-and-vps34-activity-are-essential-to-anti-atrophic-effects-of-leucine-in-skeletal-muscle
#18
Igor L Baptista, João G Silvestre, William J Silva, Siegfried Labeit, Anselmo S Moriscot
Our aim is to gain insight into the mechanisms underlying the anti-atrophic effects of leucine, namely, the way that this amino acid can restrain the up-regulation of MuRF1 and Mafbx/Atrogin-1 in muscle atrophy. Male rats received dietary leucine supplementation for 1-3 days, during which time their hind limbs were immobilized. Our results showed that leucine inhibited Forkhead Box O3 (FoxO3a) translocation to cell nuclei. In addition, leucine was able to reverse the expected reduction of FoXO3a ubiquitination caused by immobilization...
April 24, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28432521/intermittent-food-restriction-initiated-late-in-life-prolongs-lifespan-and-retards-the-onset-of-age-related-markers-in-the-annual-fish-nothobranchius-guentheri
#19
Xia Wang, Xiaoyuan Du, Yang Zhou, Su Wang, Feng Su, Shicui Zhang
Two of the most studied and widely accepted conjectures on possible aging mechanisms are the oxidative stress hypothesis and the insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) pathway. Intermittent fasting (IF) is known to modulate aging and to prolong lifespan in a variety of organisms, but the mechanisms are still under debate. In this study, we first demonstrated that late-onset two consecutive days a week fasting, a form of IF, termed intermittent food restriction (IFR), exhibited a time-dependent effect, and long-term late-onset IFR extended the mean lifespan and maximum lifespan by approximately 3...
June 2017: Biogerontology
https://www.readbyqxmd.com/read/28427239/foxo3a-dependent-bim-transcription-protects-mice-from-a-high-fat-diet-via-inhibition-of-activation-of-the-nlrp3-inflammasome-by-facilitating-autophagy-flux-in-kupffer-cells
#20
Yan Liu, Wenfeng Zhang, Xiaoling Wu, Jianping Gong
BACKGROUND: The role of Foxo3a in the regulation of autophagy flux and activation of the NLRP3 inflammasome in KCs suffering from HFD conditions is unknown. RESULTS: Up-regulation of Foxo3a restored autophagy flux and dampened the activation of the NLRP3 inflammasome in KCs stimulated with PA and LPS. In contrast, down-regulation of Foxo3a increased blockage of autophagy flux and promoted NLRP3 inflammasome activation. Additionally, mRNA levels of Bim were significantly changed with the alteration of Foxo3a in KCs under PA and LPS stimulation among foxo3a targeted genes...
May 23, 2017: Oncotarget
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