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https://www.readbyqxmd.com/read/29780898/sumoylation-and-phosphorylation-cross-talk-in-hepatocellular-carcinoma
#1
REVIEW
Maria Lauda Tomasi, Komal Ramani
Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and occurs predominantly in patients with underlying chronic liver disease and cirrhosis. The large spectrum of protein post-translational modification (PTM) includes numerous critical signaling events that occur during neoplastic transformation. PTMs occur to nearly all proteins and increase the functional diversity of proteins. We have reviewed the role of two major PTMs, SUMOylation and phosphorylation, in the altered signaling of key players in HCC...
2018: Translational Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29780505/macrophage-mediated-delivery-of-light-activated-nitric-oxide-prodrugs-with-spatial-temporal-and-concentration-control
#2
Michael A Evans, Po-Ju Huang, Yuji Iwamoto, Kelly N Ibsen, Emory M Chan, Yutaka Hitomi, Peter C Ford, Samir Mitragotri
Nitric oxide (NO) holds great promise as a treatment for cancer hypoxia, if its concentration and localization can be precisely controlled. Here, we report a "Trojan Horse" strategy to provide the necessary spatial, temporal, and dosage control of such drug-delivery therapies at targeted tissues. Described is a unique package consisting of (1) a manganese-nitrosyl complex, which is a photoactivated NO-releasing moiety (photoNORM), plus Nd3+ -doped upconverting nanoparticles (Nd-UCNPs) incorporated into (2) biodegradable polymer microparticles that are taken up by (3) bone-marrow derived murine macrophages...
April 21, 2018: Chemical Science
https://www.readbyqxmd.com/read/29772792/metabolic-regulation-of-hypoxia-inducible-transcription-factors-the-role-of-small-molecule-metabolites-and-iron
#3
REVIEW
Peter S J Bailey, James A Nathan
Hypoxia-inducible transcription factors (HIFs) facilitate cellular adaptations to low-oxygen environments. However, it is increasingly recognised that HIFs may be activated in response to metabolic stimuli, even when oxygen is present. Understanding the mechanisms for the crosstalk that exists between HIF signalling and metabolic pathways is therefore important. This review focuses on the metabolic regulation of HIFs by small molecule metabolites and iron, highlighting the latest studies that explore how tricarboxylic acid (TCA) cycle intermediates, 2-hydroxyglutarate (2-HG) and intracellular iron levels influence the HIF response through modulating the activity of prolyl hydroxylases (PHDs)...
May 17, 2018: Biomedicines
https://www.readbyqxmd.com/read/29772209/prolyl-hydroxylase-2-a-promising-target-to-inhibit-hypoxia-induced-cellular-metabolism-in-cancer-cells
#4
REVIEW
Lakhveer Singh, Sara Aldosary, Abdulaziz S Saeedan, M Nazam Ansari, Gaurav Kaithwas
Hypoxia-inducible factor-1α (HIF-1α) shifts the metabolism of glucose from highly efficient oxidative phosphorylation to less efficient glycolysis. Pyruvic acid thus accumulated is oxidized to lactic acid which is pumped out in the tumor microenvironment. Protons generated from the pentose phosphate pathway (PPP) and upon hydrolysis of ATP further enhance the acidity in the tumor microenvironment. The resultant pH in the tumor microenvironment activates an endoplasmic reticulum protein: sterol regulatory element binding protein-1c (SREBP-1c), which once activated enhances proliferation of the tumor cell...
May 14, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29770483/melatonin-modulates-dysregulated-circadian-clocks-in-mice-with-diethylnitrosamine-induced-hepatocellular-carcinoma
#5
Diana I Sánchez, Bárbara González-Fernández, Irene Crespo, Beatriz San-Miguel, Marcelino Álvarez, Javier González-Gallego, María Jesús Tuñón
Disruption of circadian rhythms, which are regulated by the circadian clock machinery, plays an important role in different long-term diseases including hepatocellular carcinoma (HCC). Melatonin has been reported to alleviate promotion and progression of HCC, but the potential contribution of circadian clock modulation is unknown. We investigated the effects of melatonin in mice which received diethylnitrosamine (DEN) (35 mg/kg body weight i.p.) once a week for 8 weeks. Melatonin was given at 5 or 10 mg/kg/day i...
May 16, 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29768539/evaluation-of-prophylactic-and-therapeutic-effects-of-sildenafil-on-acute-radiation-proctitis-in-rats
#6
Erkan Yavuz, Gulcin Ercan, Onur Olgac Karagulle, Busra Yaprak Bayrak, Aytac Biricik, Candas Ercetin, Berk Gokcek, Hakan Yigitbas, Ramazan Kusaslan, Atilla Celik, Osman Bilgin Gulcicek
PURPOSE: To investigate the prophylactic and therapeutical effects of sildenafil in a model of acute radiation proctitis (ARP). METHODS: All experimental procedures of this study was examined by histopathological, immunohistochemical and transmission electron microscopic analysis. RESULTS: Our histopathological evaluations indicated significant increases in lesion severity, cryptic apsis, cryptitis, cryptic distortion, reactive atypia and infiltration depth of the control (proctitis) group...
April 2018: Acta Cirúrgica Brasileira
https://www.readbyqxmd.com/read/29768513/increased-mitochondrial-fission-is-critical-for-hypoxia-induced-pancreatic-beta-cell-death
#7
Da Zhang, Yanfang Liu, Yao Tang, Xiaofeng Wang, Zhichao Li, Rui Li, Zhenyu Ti, Weidong Gao, Jigang Bai, Yi Lv
Hypoxia-mediated pancreatic beta cell death is one of the main causes of pancreatic beta celldeath, which leads to the loss of functional pancreatic beta cell mass and type 1 diabetes andtype 2 diabetes.However, the molecular mechanisms that control life and death of pancreatic beta cells remain poorly understood. Here we showed that mitochondrial fission was strongly induced in pancreatic beta cellsmainly due to an elevation of DRP1S616 phosphorylation through HIF-1αactivation and subsequent DRP1 mitochondrial translocation...
2018: PloS One
https://www.readbyqxmd.com/read/29764490/efficacy-of-the-hypoxia-activated-prodrug-evofosfamide-th-302-in-nasopharyngeal-carcinoma-in-vitro-and-in-vivo
#8
Yan Huang, Ying Tian, Yuanyuan Zhao, Cong Xue, Jianhua Zhan, Lin Liu, Xiaobo He, Li Zhang
BACKGROUND: Tumor hypoxia is considered an important factor in metastasis and disease relapse. Evofosfamide is a hypoxia-activated prodrug that selectively targets the hypoxic regions of solid tumors. As hypoxia-inducible factor-1α (HIF-1α) is overexpressed in nasopharyngeal carcinoma (NPC) tissues, we performed the present study to evaluate the efficacy profile of evofosfamide in NPC. METHODS: We evaluated the efficacy of evofosfamide as a single agent or combined with cisplatin (DDP) in the NPC cell lines CNE-2, HONE-1 and HNE-1, and in nude mouse xenograft tumor models...
May 3, 2018: Cancer communications
https://www.readbyqxmd.com/read/29764240/ferrous-glycinate-regulates-cell-energy-metabolism-by-restricting-hypoxia-induced-factor-1%C3%AE-expression-in-human-a549-cells
#9
Yung-Ting Kuo, Jhong-Huei Jheng, Mei-Chen Lo, Wei-Lu Chen, Shyang-Guang Wang, Horng-Mo Lee
Iron or oxygen regulates the stability of hypoxia inducible factor-1α (HIF-1α). We investigated whether ferrous glycinate would affect HIF-1α accumulation, aerobic glycolysis and mitochondrial energy metabolism in human A549 lung cancer cells. Incubation of A549 cells with ferrous glycinate decreased the protein levels of HIF-1α, which was abrogated by proteosome inhibitor, or prolyl hydroxylase inhibitor. Addition of ferrous glycinate decreased protein levels of glucose transporter-1, hexokinase-2, and lactate dehydrogenase A, and decreased pyruvate dehydrogenase kinase-1 (PDK-1) and pyruvate dehydrogenase (PDH) phosphorylation in A549 cells...
May 15, 2018: Free Radical Research
https://www.readbyqxmd.com/read/29762846/neurotrophin-3-improves-fracture-healing-in-rats
#10
X Li, D-C Sun, Y Li, X-Y Wu
OBJECTIVE: This study aimed at investigating the role of Neurotrophin-3 (NT-3) in the bone fracture healing of rats and to provide a reference for clinical treatment. MATERIALS AND METHODS: 40 Sprague-Dawley (SD) rats were randomly divided into control group and NT-3 group. The tibia fracture model was made in NT-3 group, and the tibia bone mineral density (BMD) was measured before and after the surgery. The biomechanics indexes were inspected after the surgery, including elasticity modulus, max load, and bending rigidity...
April 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29761922/fm19g11-inhibits-o-6-methylguanine-dna-methyltransferase-expression-under-both-hypoxic-and-normoxic-conditions
#11
Chao-Guo You, Han-Song Sheng, Chao-Ran Xie, Nu Zhang, Xue-Sheng Zheng
FM19G11 is a small molecular agent that inhibits hypoxia-inducible factor-1-alpha (HIF-1α) and other signaling pathways. In this study, we characterized the modulating effects of FM19G11 on O6 -methylguanine DNA-methyltransferase (MGMT), the main regulator of temozolomide (TMZ) resistance in glioblastomas. This study included 2 MGMT-positive cell lines (GBM-XD and T98G). MGMT promoter methylation status, mRNA abundance, and protein levels were determined before and after FM19G11 treatment, and the roles of various signaling pathways were characterized...
May 15, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29761172/loss-of-hypoxia-inducible-factor-1%C3%AE-aggravates-%C3%AE-%C3%AE-t-cell-mediated-inflammation-during-acetaminophen-induced-liver-injury
#12
Tomohiro Suzuki, Shoko Minagawa, Takashi Yamazaki, Takatomo Arai, Mai Kanai, Satoko Shinjo, Nobuhito Goda
Acetaminophen (APAP)-induced liver injury is closely associated with acute hepatic inflammation. Hypoxia-inducible factor-1 (HIF-1) is activated during immunological processes and regulates gene expressions in various types of immune cells. Although HIF-1 controls the differentiation and functions of conventional T cells in chronic inflammation, the pathological importance of HIF-1 in innate-like T cells during acute inflammation remains unknown. Here, we investigated the role of HIF-1 in innate-like γδ T cells during APAP-induced acute liver injury...
May 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29755339/therapeutic-potential-of-a-prolyl-hydroxylase-inhibitor-fg-4592-for-parkinson-s-diseases-in-vitro-and-in-vivo-regulation-of-redox-biology-and-mitochondrial-function
#13
Xuan Li, Xin-Xin Cui, Ya-Jing Chen, Ting-Ting Wu, Huaxi Xu, Huiyong Yin, Yun-Cheng Wu
As the main transcription factor that regulates the cellular responses to hypoxia, Hypoxia-inducible factor-1α (HIF-1α) plays an important role in the pathogenesis of Parkinson's disease (PD). HIF-1α is normally degraded through ubiquitination after hydroxylation by prolyl hydroxylases (PHD). Emerging evidence has suggested that HIF PHD inhibitors (HIF-PHI) may have neuroprotective effects on PD through increasing HIF-1α levels. However, the therapeutic benefit of HIF-PHI for PD remains poorly explored due to the lack of proper clinical compounds and understanding of the underlying molecular mechanisms...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29754996/dce-mri-in-human-gliomas-a-surrogate-for-assessment-of-invasive-hypoxia-marker-hif-1%C3%AE-based-on-mri-neuronavigation-stereotactic-biopsies
#14
Qian Xie, Juan Wu, Zunguo Du, Ningning Di, Ren Yan, Haopeng Pang, Teng Jin, Hua Zhang, Yue Wu, Yong Zhang, Zhenwei Yao, Xiaoyuan Feng
RATIONALE AND OBJECTIVES: The purpose of this study was to correlate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters with data from a specific marker of hypoxia, hypoxia-inducible factor 1α (HIF-1α), in human gliomas on a point-to-point basis by using coregistered magnetic resonance imaging and frameless stereotactic biopsies. MATERIALS AND METHODS: Thirty-four patients with treatment-naive gliomas underwent DCE, axial T1-weighted, T2-weighted, T2-weighted fluid acquisition of inversion recovery, and three-dimensional T1-weighted brain volume with gadolinium contrast enhancement sequences on a 3...
May 10, 2018: Academic Radiology
https://www.readbyqxmd.com/read/29753285/chitin-synthesis-inhibitors-promote-liver-cancer-cell-metastasis-via-interfering-with-hypoxia-inducible-factor-1%C3%AE
#15
Xia Ning, Yue Wang, Wei Yan, Guangke Li, Nan Sang
Chitin synthesis inhibitors (CSIs), as alternatives to conventional insecticides, have been in worldwide demand in recent years. However, little attention has been paid to the potential ecological safety and health risks of CSIs, especially their abilities to interfere with nonsexual hormone receptors such as hypoxia-inducible factor 1α (HIF-1α). In this work, we conducted a systematic study regarding the influence of CSIs on HIF-1α-related liver cancer cell metastasis. The dual-luciferase reporter gene assay revealed that two of fourteen CSIs exhibited dose-response HIF-1α agonistic activities at noncytotoxic concentrations with relative luciferase activity (RLA) values of 25...
May 3, 2018: Chemosphere
https://www.readbyqxmd.com/read/29749475/mir-125a-induces-apoptosis-metabolism-disorder-and-migrationimpairment-in-pancreatic-cancer-cells-by-targeting-mfn2-related-mitochondrial-fission
#16
Lichao Pan, Lin Zhou, Weijia Yin, Jia Bai, Rong Liu
Mitochondrial fission is important for the development and progression of pancreatic cancer (PC). However, little is known regarding its role in pancreatic cancer apoptosis, metabolism and migration. In the current study, the mechanism by which mitochondrial fission modifies the biological characteristics of PC was explored. MicroRNA‑125a (miR‑125a) had the ability to inhibit mitochondrial fission and contributed to cellular survival. Suppressed mitochondrial fission led to a reduction in mitochondrial debris, preserved the mitochondrial membrane potential, inhibited mitochondrial permeability transition pore opening, ablated cytochrome c leakage into the cytoplasm and reduced the pro‑apoptotic protein contents, finally blocking mitochondria related apoptosis pathways...
April 26, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29749460/role-of-txndc5-in-tumorigenesis-of-colorectal-cancer-cells-in-vivo-and-in-vitro-evidence
#17
Fengbo Tan, Hong Zhu, Xiao He, Nanhui Yu, Xingwen Zhang, Haifan Xu, Haiping Pei
Thioredoxin domain‑containing 5 (TXNDC5) is reportedly overexpressed in colorectal cancer (CRC) and is therefore considered an oncogene. However, the role of TXNDC5 in CRC tumorigenesis remains unclear. The present study aimed to explore the role of TXNDC5 in CRC tumorigenesis in vitro and in vivo under hypoxic and normoxic conditions. Analyses of patient tissue samples revealed a positive association between the expression of hypoxia‑inducible factor‑1α (HIF‑1α) or TXNDC5 and the TNM stage of CRC...
May 9, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29748743/erythropoietin-and-nrf2-key-factors-in-the-neuroprotection-provided-by-apo-lactoferrin
#18
E T Zakharova, A V Sokolov, N N Pavlichenko, V A Kostevich, I N Abdurasulova, A V Chechushkov, I V Voynova, A Yu Elizarova, N N Kolmakov, M G Bass, I V Semak, A I Budevich, P M Kozhin, N K Zenkov, V M Klimenko, O V Kirik, D E Korzhevskii, E B Menshchikova, V B Vasilyev
Among the properties of lactoferrin (LF) are bactericidal, antianemic, immunomodulatory, antitumour, antiphlogistic effects. Previously we demonstrated its capacity to stabilize in vivo HIF-1-alpha and HIF-2-alpha, which are redox-sensitive multiaimed transcription factors. Various tissues of animals receiving recombinant human LF (rhLF) responded by expressing the HIF-1-alpha target genes, hence such proteins as erythropoietin (EPO), ceruloplasmin, etc. were synthesized in noticeable amounts. Among organs in which EPO synthesis occurred were brain, heart, spleen, liver, kidneys and lungs...
May 10, 2018: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/29748146/discovery-of-bicyclo-3-3-1-non-2-ene-as-a-novel-skeleton-for-hif-1-inhibitors
#19
Hiroki Ueda, Atsushi Yoshimori, Hiroyuki Nakamura
Bicyclo[3,3,1]non-2-ene was used as a novel three-dimensional skeleton for the design and synthesis of hypoxia-inducible factor (HIF)-1 inhibitors. Among the compounds synthesized, compound 4b was found to be a potent inhibitor of HIF-1α protein accumulation under hypoxia and inhibited HIF-1α transcriptional activity in HeLa (human cervical carcinoma) cells (half maximal inhibitory concentration [IC50 ] = 3.0 μM). The inhibition of HIF-1α accumulation induced by compound 4b was attenuated by treating the cells with MG132, a proteasome inhibitor, in a concentration-dependent manner, indicating that the compound 4b induces oxygen-independent proteasomal degradation of HIF-1α...
May 3, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29747407/transcription-factors-as-therapeutic-targets-in-chronic-kidney-disease
#20
REVIEW
Akihito Hishikawa, Kaori Hayashi, Hiroshi Itoh
The growing number of patients with chronic kidney disease (CKD) is recognized as an emerging problem worldwide. Recent studies have indicated that deregulation of transcription factors is associated with the onset or progression of kidney disease. Several clinical trials indicated that regression of CKD may be feasible via activation of the transcription factor nuclear factor erythroid-2 related factor 2 (Nrf2), which suggests that transcription factors may be potential drug targets for CKD. Agents stabilizing hypoxia-inducible factor (HIF), which may be beneficial for renal anemia and renal protection, are also now under clinical trial...
May 9, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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