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https://www.readbyqxmd.com/read/28106131/hif-1%C3%AE-induction-during-reperfusion-avoids-maladaptive-repair-after-renal-ischemia-reperfusion-involving-mir127-3p
#1
Elisa Conde, Sara Giménez-Moyano, Laura Martín-Gómez, Macarena Rodríguez, M Edurne Ramos, Elia Aguado-Fraile, Ignacio Blanco-Sanchez, Ana Saiz, María Laura García-Bermejo
Ischemia/reperfusion (I/R) leads to Acute Kidney Injury. HIF-1α is a key factor during organ response to I/R. We previously demonstrated that HIF-1α is induced during renal reperfusion, after ischemia. Here we investigate the role of HIF-1α and the HIF-1α dependent mechanisms in renal repair after ischemia. By interference of HIF-1α in a rat model of renal I/R, we observed loss of expression and mis-localization of e-cadherin and induction of α-SMA, MMP-13, TGFβ, and collagen I. Moreover, we demonstrate that HIF-1α inhibition promotes renal cell infiltrates by inducing IL-1β, TNF-α, MCP-1 and VCAM-1, through NFkB activity...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28105937/effect-of-lentivirus-mediated-shrna-inactivation-of-hk1-hk2-and-hk3-genes-in-colorectal-cancer-and-melanoma-cells
#2
Anna V Kudryavtseva, Maria S Fedorova, Alex Zhavoronkov, Alexey A Moskalev, Alexander S Zasedatelev, Alexey A Dmitriev, Asiya F Sadritdinova, Irina Y Karpova, Kirill M Nyushko, Dmitry V Kalinin, Nadezhda N Volchenko, Nataliya V Melnikova, Kseniya M Klimina, Dmitry V Sidorov, Anatoly Y Popov, Tatiana V Nasedkina, Andrey D Kaprin, Boris Y Alekseev, George S Krasnov, Anastasiya V Snezhkina
BACKGROUND: The switch from oxidative phosphorylation to glycolysis in proliferating cancer cells, even under aerobic conditions, has been shown first in 1926 by Otto Warburg. Today this phenomenon is known as the "Warburg effect" and recognized as a hallmark of cancer. The metabolic shift to glycolysis is associated with the alterations in signaling pathways involved in energy metabolism, including glucose uptake and fermentation, and regulation of mitochondrial functions. Hexokinases (HKs), which catalyze the first step of glycolysis, have been identified to play a role in tumorigenesis of human colorectal cancer (CRC) and melanoma...
December 22, 2016: BMC Genetics
https://www.readbyqxmd.com/read/28098871/lectin-pcl-inhibits-the-warburg-effect-of-pc3-cells-by-combining-with-egfr-and-inhibiting-hk2
#3
Hong Zhang, Xia Du, Ting-Ting Sun, Chun-Liu Wang, Ye Li, Shou-Zhen Wu
Prostatic carcinoma is the most aggressive tumor in adult men. Warburg effect is an important characteristic of tumor cell metabolism including prostate cancer cells, in which hexokinase 2 (HK2), a major rate-limiting enzyme involved in Warburg effect, is selectively upregulated. The lectin PCL is a mannose binding lectin which induces tumor cell apoptosis and autophagy. In the present study, we report that PCL could lower glucose consumption and lactate production, shift the Warburg effect by inhibiting the expression of HK2 in PC3 cells and the suppression of HK2 by siRNA reversed the effect of PCL on glucose consumption and lactate production...
January 16, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28088654/transcriptional-response-of-skeletal-muscle-to-a-low-protein-perinatal-diet-in-rat-offspring-at-different-ages-the-role-of-key-enzymes-of-glucose-fatty-acid-oxidation
#4
José Luiz de Brito Alves, Ana Elisa Toscano, João Henrique da Costa-Silva, Hubert Vidal, Carol Góis Leandro, Luciano Pirola
Skeletal muscle is a plastic tissue during development with distinctive acute and chronic response to maternal protein restriction. This study evaluated gene and protein expression of key-enzymes of glycolytic pathway (HK2, PFK, PDK4 and CS), and fatty acid oxidation (CPT1 and β-HAD) of two different types of skeletal muscle [soleus and extensor digitorium longus (EDL)] from offspring rats at 30 and 90 days of age, exposed to maternal isoenergetic low protein diet throughout gestation and lactation. Pups from dams fed 17% protein diet (n=5, normal protein, Np), and low protein pups from dams fed 8% casein diet (low protein, Lp, n=5) were evaluated...
December 15, 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28086949/nek2-promotes-aerobic-glycolysis-in-multiple-myeloma-through-regulating-splicing-of-pyruvate-kinase
#5
Zhimin Gu, Jiliang Xia, Hongwei Xu, Ivana Frech, Guido Tricot, Fenghuang Zhan
BACKGROUND: Aerobic glycolysis, a hallmark of cancer, is characterized by increased metabolism of glucose and production of lactate in normaxia. Recently, pyruvate kinase M2 (PKM2) has been identified as a key player for regulating aerobic glycolysis and promoting tumor cell proliferation and survival. METHODS: Tandem affinity purification followed up by mass spectrometry (TAP-MS) and co-immunoprecipitation (Co-IP) were used to study the interaction between NIMA (never in mitosis gene A)-related kinase 2 (NEK2) and heterogeneous nuclear ribonucleoproteins (hnRNP) A1/2...
January 13, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28077391/acclimation-to-hypoxia-increases-carbohydrate-use-during-exercise-in-high-altitude-deer-mice
#6
Daphne S Lau, Alex D Connaty, Sajeni Mahalingam, Nastashya Wall, Zachary A Cheviron, Jay F Storz, Graham R Scott, Grant B McClelland
The low oxygen experienced at high altitude is a significant challenge to effective aerobic locomotion, as it requires sustained tissue oxygen delivery in addition to the appropriate allocation of metabolic substrates. Here we test whether high- and low-altitude deer mice (Peromyscus maniculatus) have evolved different acclimation responses to hypoxia with respect to muscle metabolism and fuel use during submaximal exercise. Using F1-generation high- and low-altitude deer mice that were born and raised in common conditions, we assessed 1) fuel use during exercise, 2) metabolic enzyme activities, and 3) gene expression for key transporters and enzymes in the gastrocnemius...
January 11, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28075049/src-homology-2-domain-containing-inositol-5-phosphatase-ameliorates-high-glucose-induced-extracellular-matrix-deposition-via-the-phosphatidylinositol-3-kinase-protein-kinase-b-pathway-in-renal-tubular-epithelial-cells
#7
Fan Li, Lisha Li, Jun Hao, Shuxia Liu, Huijun Duan
A typical hallmark of diabetic kidney disease (DKD) is an excessive deposition of extracellular matrix (ECM) in the glomerulus and renal tubulointerstitium, leading to glomerulosclerosis and tubular interstitial fibrosis. Src homology 2 domain-containing inositol 5'-phosphatase (SHIP) is a negative regulator of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling. Here, we investigated the effect of SHIP on ECM deposition in diabetic mice and high glucose-stimulated human renal tubular epithelial cells (HK2 cells)...
January 11, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28069585/expression-of-hmgb2-indicates-worse-survival-of-patients-and-is-required-for-the-maintenance-of-warburg-effect-in-pancreatic-cancer
#8
Xin Cai, Hongjian Ding, Yanxia Liu, Gaofeng Pan, Qingguo Li, Zhen Yang, Weiyan Liu
High mobility group proteins (HMGs) are the second most abundant chromatin proteins and exert global genomic functions in the establishment of active or inactive chromatin domains. Through interaction with nucleosomes, transcription factors, nucleosome-remodeling machines and histones, the HMGs family proteins contribute to the fine tuning of transcription in response to rapid environmental changes. Mammalian high mobility group Bs (HMGBs) are characterized by two tandem HMG box domains followed by a long acidic tail...
January 9, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28069424/different-regulation-of-insulin-on-glucose-and-lipid-metabolism-in-2-strains-of-gibel-carp
#9
Junyan Jin, Xiaoming Zhu, Dong Han, Yunxia Yang, Haokun Liu, Shouqi Xie
To test the hypothesis that response to insulin by regulating glucose and lipid metabolism in gibel carp A strain may be different from that in DT strain, bovine insulin was injected into both strains of gibel carp after previous fasting for 48 h. The results showed that insulin induced hypoglycemia at 3 h in 2 strains, and that this was coupled with increased expression of glucose transporters (GLUT2 in the liver and GLUT1, GLUT4 in the muscle) and glycolytic enzyme (HK2 in the muscle) in both strains. Insulin induced increased glycolysis (GK) and fatty acid oxidation (ACO3 in the liver and CPT1a, ACO3 in the muscle) in the DT strain...
January 6, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28063928/mir-107-induces-tnf-%C3%AE-secretion-in-endothelial-cells-causing-tubular-cell-injury-in-patients-with-septic-acute-kidney-injury
#10
Shanshan Wang, Zengdi Zhang, Jun Wang, Hongjun Miao
Activation of endothelial cells plays a key role in septic acute kidney injury (AKI). This study investigated the role of miRNA in endothelial-induced tubular cell injury in sepsis. Circulating endothelial cells (CECs) from septic AKI, non-septic AKI, septic non-AKI patients and healthy volunteers were isolated and cultured, and HK2 cells were exposed to CEC-conditioned medium. CEC-conditioned medium prepared from septic AKI patients led to cell shrinkage, decreased E-cadherin, the release of NAG and cell apoptosis in HK2 cells...
January 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28056994/hexokinase-2-drives-glycogen-accumulation-in-equine-endometrium-at-day-12-of-diestrus-and-pregnancy
#11
Sarah A Bramer, Alysson Macedo, Claudia Klein
BACKGROUND: Secretion of histotroph during the prolonged pre-implantation phase in mares is crucial to pregnancy maintenance, manifested as increased embryonic loss in mares with age-related endometrial degeneration. Glycogen content of uterine histotroph is higher during the progesterone-dominated phase of the estrous cycle in mares, but regulatory mechanisms are not well understood. METHODS: mRNA expression of glycogen-metabolizing enzymes (HK1, HK2, GSK3B, GYS1, PEPCK, PKM, PYGM) in endometrial samples were compared among mares in anestrus, estrus, and at Day 12 of diestrus and pregnancy...
January 5, 2017: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/28054552/c-src-phosphorylation-and-activation-of-hexokinase-promotes-tumorigenesis-and-metastasis
#12
Jia Zhang, Suili Wang, Bin Jiang, Lihong Huang, Zhiliang Ji, Xiaotong Li, Huamin Zhou, Aidong Han, Ai Chen, Yanan Wu, Huanhuan Ma, Wentao Zhao, Qingwen Zhao, Changchuan Xie, Xiaoyan Sun, Yanming Zhou, Huiying Huang, Muhammad Suleman, Furong Lin, Lin Zhou, Fang Tian, Meijun Jin, Yana Cai, Nan Zhang, Qinxi Li
It is well known that c-Src has important roles in tumorigenesis. However, it remains unclear whether c-Src contributes to metabolic reprogramming. Here we find that c-Src can interact with and phosphorylate hexokinases HK1 and HK2, the rate-limiting enzymes in glycolysis. Tyrosine phosphorylation dramatically increases their catalytic activity and thus enhances glycolysis. Mechanistically, c-Src phosphorylation of HK1 at Tyr732 robustly decreases its Km and increases its Vmax by disrupting its dimer formation...
January 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28049552/antiproliferative-cyclodepsipeptides-from-the-marine-actinomycete-streptomyces-sp-p11-23b-downregulating-the-tumor-metabolic-enzymes-of-glycolysis-glutaminolysis-and-lipogenesis
#13
Xuewei Ye, Komal Anjum, Tengfei Song, Wenling Wang, Ying Liang, Mengxuan Chen, Haocai Huang, Xiao-Yuan Lian, Zhizhen Zhang
Two cyclodepsipeptides and a known cyclodepsipeptide valinomycin were isolated from a culture of the marine actinomycete Streptomyces sp. P11-23B. Their structures were established based on NMR, HRESIMS, and MS-MS spectroscopic interpretation as well as by chemical degradation. Both streptodepsipeptides P11A and P11B inhibited proliferation of different glioma cell lines, with IC50 values ranging from 0.1 μM to 1.4 μM. Streptodepsipeptide P11A was found to block the cell cycle at the G0/G1 phase and induce apoptosis in glioma cells...
December 31, 2016: Phytochemistry
https://www.readbyqxmd.com/read/28046212/su-f-t-677-synergistic-effect-s-of-clotrimazole-on-radiation-cell-survival-of-a549-lung-cancer-cells-in-glucose-vs-galactose-media
#14
G Boss, M Tambasco, M Garakani
PURPOSE: In order to determine the synergistic effect of clotrimazole on radiosensitivity of A549 lung cancer cells, and the effect of oxidative pathways on modulating radiosensitivity, we studied how these cells survived under varying amounts of radiation and clotrimazole as well ass when glucose was switched for galactose media. METHODS: The glucose media was used to determine the presence of any synergistic effect of clotrimazole on radiation using values of radiation and clotrimazole concentrations, varying from 0 - 8 Gy and 0 - 20 µM, respectively...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28036282/sulodexide-pretreatment-attenuates-renal-ischemia-reperfusion-injury-in-rats
#15
Jianyong Yin, Weibin Chen, Fenfen Ma, Zeyuan Lu, Rui Wu, Guangyuan Zhang, Niansong Wang, Feng Wang
Sulodexide is a potent antithrombin agent, however, whether it has beneficial effects on renal ischemia-reperfusion injury (IRI) remains unknown. In the present study, we assessed the therapeutic effects of sulodexide in renal IRI and tried to investigate the potential mechanism. One dose of sulodexide was injected intravenously in Sprague-Dawley rats 30 min before bilateral kidney ischemia for 45 min. The animals were sacrificed at 3h and 24h respectively. Our results showed that sulodexide pretreatment improved renal dysfunction and alleviated tubular pathological injury at 24h after reperfusion, which was accompanied with inhibition of oxidative stress, inflammation and cell apoptosis...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28025745/microrna-98-suppress-warburg-effect-by-targeting-hk2-in-colon-cancer-cells
#16
Weimin Zhu, Yijiao Huang, Qi Pan, Pei Xiang, Nanlan Xie, Hao Yu
BACKGROUND: Warburg effect is a hallmark of cancer cells. Accumulating evidence suggests that microRNAs (miRs) could regulate such metabolic reprograming. Aberrant expression of miR-98 has been observed in many types of cancers. However, its functions and significance in colon cancer remain largely elusive. AIMS: To investigate miR-98 expression and the biological functions in colon cancer progression. METHODS: miR-98 expression levels were determined by quantitative RT-PCR in 215 cases of colon cancer samples...
December 26, 2016: Digestive Diseases and Sciences
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
#17
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/27983708/the-hk2-dependent-warburg-effect-and-mitochondrial-oxidative-phosphorylation-in-cancer-targets-for-effective-therapy-with-3-bromopyruvate
#18
REVIEW
Paweł Lis, Mariusz Dyląg, Katarzyna Niedźwiecka, Young H Ko, Peter L Pedersen, Andre Goffeau, Stanisław Ułaszewski
This review summarizes the current state of knowledge about the metabolism of cancer cells, especially with respect to the "Warburg" and "Crabtree" effects. This work also summarizes two key discoveries, one of which relates to hexokinase-2 (HK2), a major player in both the "Warburg effect" and cancer cell immortalization. The second discovery relates to the finding that cancer cells, unlike normal cells, derive as much as 60% of their ATP from glycolysis via the "Warburg effect", and the remaining 40% is derived from mitochondrial oxidative phosphorylation...
December 15, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27982118/brusatol-inhibits-hif-1-signaling-pathway-and-suppresses-glucose-uptake-under-hypoxic-conditions-in-hct116-cells
#19
Yapeng Lu, Bo Wang, Qian Shi, Xueting Wang, Dang Wang, Li Zhu
Hypoxia-inducible factor-1 (HIF-1) is an important transcription factor that induces adaptive responses upon low oxygen conditions in human cancers and triggers off a poor prognostic outcome of conventional treatments. In this study, we discovered for the first time that brusatol (BRU), a quassinoid extracted from Brucea Esters, has the capability to inhibit HIF-1 signaling pathway. We found that BRU concentration-dependently down-regulated HIF-1α protein levels under hypoxia or CoCl2-induced mimic hypoxia in HCT116 cells without causing significant cytotoxicity...
December 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27965087/ship-a-novel-factor-to-ameliorate-extracellular-matrix-accumulation-via-suppressing-pi3k-akt-ctgf-signaling-in-diabetic-kidney-disease
#20
Fan Li, Lisha Li, Meijuan Cheng, Xiumin Wang, Jun Hao, Shuxia Liu, Huijun Duan
Tubular interstitial extracellular matrix accumulation, which plays a key role in the pathogenesis and progression of diabetic kidney disease (DKD), is believed to be mediated by activation of PI3K/Akt signal pathway. However, it is still not clear whether SH2 domain-containing inositol 5'-phosphatase (SHIP), known as a negative regulator of PI3K/Akt pathway is also involved in extracellular matrix metabolism of diabetic kidney. In the present study, decreased SHIP and increased phospho-Akt (Ser 473, Thr 308) were found in renal tubular cells of diabetic mice accompanied by overexpression of connective tissue growth factor (CTGF) and extracellular matrix deposition versus normal mice...
January 22, 2017: Biochemical and Biophysical Research Communications
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