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https://www.readbyqxmd.com/read/28290047/adaptation-to-chronic-continuous-hypoxia-potentiates-akt-hk2-anti-apoptotic-pathway-during-brief-myocardial-ischemia-reperfusion-insult
#1
David Kolar, Milada Gresikova, Petra Waskova-Arnostova, Barbara Elsnicova, Jana Kohutova, Daniela Hornikova, Pavel Vebr, Jan Neckar, Tereza Blahova, Dita Kasparova, Jiri Novotny, Frantisek Kolar, Olga Novakova, Jitka M Zurmanova
Adaptation to chronic hypoxia represents a potential cardioprotective intervention reducing the extent of acute ischemia/reperfusion (I/R) injury, which is a major cause of death worldwide. The main objective of this study was to investigate the anti-apoptotic Akt/hexokinase 2 (HK2) pathway in hypoxic hearts subjected to I/R insult. Hearts isolated from male Wistar rats exposed either to continuous normobaric hypoxia (CNH; 10% O2) or to room air for 3 weeks were perfused according to Langendorff and subjected to 10 min of no-flow ischemia and 10 min of reperfusion...
March 13, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28288978/mff-dependent-mitochondrial-fission-contributes-to-the-pathogenesis-of-cardiac-microvasculature-ischemia-reperfusion-injury-via-induction-of-mros-mediated-cardiolipin-oxidation-and-hk2-vdac1-disassociation-involved-mptp-opening
#2
Hao Zhou, Shunying Hu, Qinhua Jin, Chen Shi, Ying Zhang, Pingjun Zhu, Qiang Ma, Feng Tian, Yundai Chen
BACKGROUND: The cardiac microvascular system ischemia/reperfusion injury following percutaneous coronary intervention is a clinical thorny problem. This study explores the mechanisms by which ischemia/reperfusion injury induces cardiac microcirculation collapse. METHODS AND RESULTS: In wild-type mice, mitochondrial fission factor (Mff) expression increased in response to acute microvascular ischemia/reperfusion injury. Compared with wild-type mice, homozygous Mff-deficient (Mff(gt)) mice exhibited a smaller infarcted area, restored cardiac function, improved blood flow, and reduced microcirculation perfusion defects...
March 13, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28288859/mitochondrial-toxicity-of-perfluorooctane-sulfonate-in-mouse-embryonic-stem-cell-derived-cardiomyocytes
#3
Lei-Lei Tang, Jia-Dan Wang, Ting-Ting Xu, Zhe Zhao, Jia-Jie Zheng, Ren-Shan Ge, Dan-Yan Zhu
Perfluorooctane sulfonate (PFOS) is a persistent organic contaminant that may cause cardiotoxicity in animals and humans. However, little is known about the underlying mechanism by which it affects the organelle toxicity in cardiomyocytes during the cardiogenesis. Our previous proteomic study showed that differences of protein expression mainly existed in mitochondria of cardiomyocytes differentiated from embryonic stem (ES) cells after exposure to PFOS. Here, we focused on mitochondrial toxicity of PFOS in ES cell-derived cardiomyocytes...
March 10, 2017: Toxicology
https://www.readbyqxmd.com/read/28264838/loss-of-brca1-in-the-cells-of-origin-of-ovarian-cancer-induces-glycolysis-a-window-of-opportunity-for-ovarian-cancer-chemoprevention
#4
Tatsuyuki Chiyoda, Peter C Hart, Mark A Eckert, Stephanie M McGregor, Ricardo R Lastra, Ryuji Hamamoto, Yusuke Nakamura, S Diane Yamada, Olufunmilayo I Olopade, Ernst Lengyel, Iris L Romero
Mutations in the breast cancer susceptibility gene 1 (BRCA1) are associated with an increased risk of developing epithelial ovarian cancer. However, beyond the role of BRCA1 in DNA repair, little is known about other mechanisms by which BRCA1 impairment promotes carcinogenesis. Given that altered metabolism is now recognized as important in the initiation and progression of cancer, we asked whether loss of BRCA1 changes metabolism in the cells of origin of ovarian cancer. The findings show that silencing BRCA1 in ovarian surface epithelial and fallopian tube cells increased glycolysis...
March 6, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28263974/histone-demethylase-jmjd1a-promotes-urinary-bladder-cancer-progression-by-enhancing-glycolysis-through-coactivation-of-hypoxia-inducible-factor-1%C3%AE
#5
W Wan, K Peng, M Li, L Qin, Z Tong, J Yan, B Shen, C Yu
High aerobic glycolysis not only provides energy to cancer cells, but also supports their anabolic growth. JMJD1A, a histone demethylase that specifically demethylates H3K9me1/2, is overexpressed in multiple cancers, including urinary bladder cancer (UBC). It is unclear whether JMJD1A could promote cancer cell growth through enhancing glycolysis. In this study, we found that downregulation of JMJD1A decreased UBC cell proliferation, colony formation and xenograft tumor growth. Knockdown of JMJD1A inhibited glycolysis by decreasing the expression of genes participated in glucose metabolism, including GLUT1, HK2, PGK1, PGM, LDHA and MCT4...
March 6, 2017: Oncogene
https://www.readbyqxmd.com/read/28260077/atorvastatin-protects-against-contrast-induced-nephropathy-via-anti-apoptosis-by-the-upregulation-of-hsp27-in%C3%A2-vivo-and-in%C3%A2-vitro
#6
Xuyu He, Junqing Yang, Liwen Li, Hong Tan, Ying Wu, Peng Ran, Shuo Sun, Jiyan Chen, Yingling Zhou
Contrast-induced nephropathy (CIN) is an iatrogenic acute renal failure occurring following the intravascular injection of iodinated radiographic contrast medium. However, the regulatory mechanisms for CIN remain to be fully elucidated. The present study aimed to investigate whether atorvastatin protects against CIN via anti‑apoptotic effects by the upregulation of Hsp27 in vivo and in vitro. To determine whether atorvastatin attenuated CIN, the inflammatory response and apoptosis in vivo and in vitro, a rat model of iopamidol‑induced CIN was used, and human embryonic proximal tubule (HK2) cell damage was assessed...
February 28, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28245463/protective-effects-of-glucagon-like-peptide-1-analog-on-renal-tubular-injury-in-mice-on-high-fat-diet
#7
Honglei Guo, Hongmei Li, Bin Wang, Wei Ding, Lilu Ling, Min Yang, Yong Gu, Jianying Niu
AIMS: The study aimed to investigate the renoprotective effect of glucagon-like peptide-1 (GLP-1) against renal tubular injury in C57BL/6 mice induced by a high-fat diet (HFD). METHODS: Twenty C57BL/6 mice were fed HFD for 12 weeks. Ten of these mice were treated with GLP-1 at 200 µg/kg subcutaneously twice daily for 4 weeks (HFDG group), and the other ten mice received vehicle only (HFD group). Ten mice fed standard rodent chow served as controls (Con group). Body weight, kidney weight, food intake, and systolic blood pressure were measured...
February 28, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28224194/mycoepoxydiene-suppresses-hela-cell-growth-by-inhibiting-glycolysis-and-the-pentose-phosphate-pathway
#8
Kehua Jin, Li Li, Xihuan Sun, Qingyan Xu, Siyang Song, Yuemao Shen, Xianming Deng
Upregulation of glycolysis and the pentose phosphate pathway (PPP) is a major characteristic of the metabolic reprogramming of cancer and provides cancer cells with energy and vital metabolites to support their rapid proliferation. Targeting glycolysis and the PPP has emerged as a promising antitumor therapeutic strategy. Marine natural products are attractive sources for anticancer therapeutics, as evidenced by the antitumor drug Yondelis. Mycoepoxydiene (MED) is a natural product isolated from a marine fungus that has shown promising inhibitory efficacy against HeLa cells in vitro...
February 21, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28215847/prostate-cancer-screening-in-men-aged-50-to-69-years-sthlm3-a-prospective-population-based-diagnostic-study-gr%C3%A3-nberg-h-adolfsson-j-aly-m-nordstr%C3%A3-m-t-wiklund-p-brandberg-y-thompson-j-wiklund-f-lindberg-j-clements-m-egevad-l-eklund-m-lancet-oncol-2015-dec-16
#9
Eggener Scott, J Adolfsson, M Aly, T Nordström, P Wiklund, Y Brandberg, J Thompson, F Wiklund, J Lindberg, M Clements, L Egevad, M Eklund
BACKGROUND: The prostate-specific antigen (PSA) test is used to screen for prostate cancer but has a high false-positive rate that translates into unnecessary prostate biopsies and overdiagnosis of low-risk prostate cancers. We aimed to develop and validate a model to identify high-risk prostate cancer (with a Gleason score of at least 7) with better test characteristics than that provided by PSA screening alone. METHODS: The Stockholm 3 (STHLM3) study is a prospective, population-based, paired, screen-positive, diagnostic study of men without prostate cancer aged 50 to 69 years randomly invited by date of birth from the Swedish Population Register kept by the Swedish Tax Agency...
March 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28213701/ursolic-acid-mediated-changes-in-glycolytic-pathway-promote-cytotoxic-autophagy-and-apoptosis-in-phenotypically-different-breast-cancer-cells
#10
Anna Lewinska, Jagoda Adamczyk-Grochala, Ewa Kwasniewicz, Anna Deregowska, Maciej Wnuk
Plant-derived pentacyclic triterpenotids with multiple biological activities are considered as promising candidates for cancer therapy and prevention. However, their mechanisms of action are not fully understood. In the present study, we have analyzed the effects of low dose treatment (5-20 µM) of ursolic acid (UA) and betulinic acid (BA) on breast cancer cells of different receptor status, namely MCF-7 (ER(+), PR(+/-), HER2(-)), MDA-MB-231 (ER(-), PR(-), HER2(-)) and SK-BR-3 (ER(-), PR(-), HER2(+)). UA-mediated response was more potent than BA-mediated response...
February 17, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28203527/superoxide-increases-angiotensin-ii-at1-receptor-function-in-human-kidney-2-cells
#11
Mohammad Saleem, Indira Pokkunuri, Mohammad Asghar
The redox-sensitive Sp family transcription factor has been linked to the regulation of angiotensin II type 1 receptor (AT1R). However, the exact mechanism of AT1R regulation in renal cells is poorly understood. We tested the specificity of reactive oxygen species (ROS), superoxide vs. hydrogen peroxide (H2O2), and the specific role of Sp3 transcription factor, if any, in the regulation of AT1R in human kidney cells (HK2 cells). Superoxide dismutase (SOD) inhibitor diethyldithiocarbamate (DETC), but not H2O2 treatment, increased fluorescence levels of superoxide probe dihydroethidium (DHE)...
December 2016: FEBS Open Bio
https://www.readbyqxmd.com/read/28199183/mrna-mirna-integrative-analysis-of-diabetes-induced-cardiomyopathy-in-rats
#12
Mariana B Lopes, Renata Cc Freitas, Mario H Hirata, Rosario Dc Hirata, Adriana A Rezende, Vivian N Silbiger, Raul H Bortolin, Andre D Luchessi
An integrative analysis of miRNA and mRNA expression profiles in left ventricle (LV) of diabetes-induced rats was performed to elucidate the role of miRNAs and their mRNAs target in diabetic cardiomyopathy (DCM). mRNA (GSE4745) and miRNA (GSE44179) datasets were downloaded from Gene Expression Omnibus 2R (GEO2R) and differentially expressed mRNAs and miRNAs were selected. Cardiotoxicity-related mRNAs (n=7) were analyzed by Ingenuity Pathway Analyses 6 (IPA) and regulatory miRNAs (n=639) were identified using TargetScan 7...
March 1, 2017: Frontiers in Bioscience (Scholar Edition)
https://www.readbyqxmd.com/read/28194038/itd-mutation-in-flt3-tyrosine-kinase-promotes-warburg-effect-and-renders-therapeutic-sensitivity-to-glycolytic-inhibition
#13
H-Q Ju, G Zhan, A Huang, Y Sun, S Wen, J Yang, W-H Lu, R-H Xu, J Li, Y Li, G Garcia-Manero, P Huang, Y Hu
Internal tandem duplication (ITD) mutation in Fms-like tyrosine kinase 3 gene (FLT3/ITD) represents an unfavorable genetic change in acute myeloid leukemia (AML) and is associated with poor prognosis. Metabolic alterations have been involved in tumor progression and attracted interest as a target for therapeutic intervention. However, few studies analyzed the adaptations of cellular metabolism in the context of FLT3/ITD mutation. Here, we report that FLT3/ITD causes a significant increase in aerobic glycolysis through AKT-mediated upregulation of mitochondrial hexokinase (HK2), and renders the leukemia cells highly dependent on glycolysis and sensitive to pharmacological inhibition of glycolytic activity...
February 14, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28191039/elevated-transcriptional-levels-of-aldolase-a-aldoa-associates-with-cell-cycle-related-genes-in-patients-with-nsclc-and-several-solid-tumors
#14
Fan Zhang, Jie-Diao Lin, Xiao-Yu Zuo, Yi-Xuan Zhuang, Chao-Qun Hong, Guo-Jun Zhang, Xiao-Jiang Cui, Yu-Kun Cui
BACKGROUND: Aldolase A (ALDOA) is one of the glycolytic enzymes primarily found in the developing embryo and adult muscle. Recently, a new role of ALDOA in several cancers has been proposed. However, the underlying mechanism remains obscure and inconsistent. In this study, we tried to investigate ALDOA-associated (AA) genes using available microarray datasets to help elucidating the role of ALDOA in cancer. RESULTS: In the dataset of patients with non-small-cell lung cancer (NSCLC, E-GEOD-19188), 3448 differentially expressed genes (DEGs) including ALDOA were identified, in which 710 AA genes were found to be positively associated with ALDOA...
2017: BioData Mining
https://www.readbyqxmd.com/read/28186160/3-bromopyruvate-ameliorate-autoimmune-arthritis-by-modulating-th17-treg-cell-differentiation-and-suppressing-dendritic-cell-activation
#15
Takaichi Okano, Jun Saegusa, Keisuke Nishimura, Soshi Takahashi, Sho Sendo, Yo Ueda, Akio Morinobu
Recent studies have shown that cellular metabolism plays an important role in regulating immune cell functions. In immune cell differentiation, both interleukin-17-producing T (Th17) cells and dendritic cells (DCs) exhibit increased glycolysis through the upregulation of glycolytic enzymes, such as hexokinase-2 (HK2). Blocking glycolysis with 2-deoxyglucose was recently shown to inhibit Th17 cell differentiation while promoting regulatory T (Treg) cell generation. However, 2-DG inhibits all isoforms of HK. Thus, it is unclear which isoform has a critical role in Th17 cell differentiation and in rheumatoid arthritis (RA) pathogenesis...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28184935/involvement-of-ezh2-in-aerobic-glycolysis-of-prostate-cancer-through-mir-181b-hk2-axis
#16
Tao Tao, Ming Chen, Ranran Jiang, Han Guan, Yeqing Huang, Huan Su, Qiang Hu, Xu Han, Jun Xiao
Recent studies suggest that several types of tumors preferentially metabolize glucose through aerobic glycolysis, a phenomenon known as the Warburg effect. However, it remains largely unexplored whether metabolic reprogramming is involved in prostate cancer (PCa) progression. In this study, we found that histone methyltransferase enhancer of zeste homolog 2 (EZH2) dysregulated in PCa development regulated cellular growth and aerobic glycolysis through miR-181b/hexokinase 2 (HK2) axis. Aberrant expression profiles of coding RNA and microRNA were examined by two large, independent clinical prostate cancer data sets...
March 2017: Oncology Reports
https://www.readbyqxmd.com/read/28179998/phlpp-regulates-hexokinase-2-dependent-glucose-metabolism-in-colon-cancer-cells
#17
Xiaopeng Xiong, Yang-An Wen, Mihail I Mitov, Mary C Oaks, Shigeki Miyamoto, Tianyan Gao
Increased glucose metabolism is considered as one of the most important metabolic alterations adapted by cancer cells in order to generate energy as well as high levels of glycolytic intermediates to support rapid proliferation. PH domain leucine-rich repeat protein phosphatase (PHLPP) belongs to a novel family of Ser/Thr protein phosphatases that function as tumor suppressors in various types of human cancer. Here we determined the role of PHLPP in regulating glucose metabolism in colon cancer cells. Knockdown of PHLPP increased the rate of glucose consumption and lactate production, whereas overexpression of PHLPP had the opposite effect...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28178341/enhanced-expression-of-two-discrete-isoforms-of-matrix-metalloproteinase-2-in-experimental-and-human-diabetic-nephropathy
#18
Sang Soo Kim, Nari Shin, Sun Sik Bae, Min Young Lee, Harin Rhee, Il Young Kim, Eun Young Seong, Dong Won Lee, Soo Bong Lee, Ihm Soo Kwak, David H Lovett, Sang Heon Song
BACKGROUND: We recently reported on the enhanced expression of two isoforms of matrix metalloproteinase-2 (MMP-2) in human renal transplantation delayed graft function. These consist of the conventional secreted, full length MMP-2 isoform (FL-MMP-2) and a novel intracellular N-Terminal Truncated isoform (NTT-MMP-2) generated by oxidative stress-mediated activation of an alternate promoter in the MMP-2 first intron. Here we evaluated the effect of hyperglycemia and diabetes mellitus on the in vitro and in vivo expression of the two MMP-2 isoforms...
2017: PloS One
https://www.readbyqxmd.com/read/28174335/microrna-143-suppresses-oral-squamous-cell-carcinoma-oscc-cell-growth-invasion-and-glucose-metabolism-through-targeting-hexokinase2
#19
Xianghui Sun, Lei Zhang
MicroRNAs are non-coding RNAs that have functions to regulate gene expression and play essential roles in a variety of biological processes of cancers. In this study, we report miR-143 acts as a tumor suppressor in human oral squamous cell carcinoma (OSCC). The expressions of miR-143 are downregulated in both oral squamous cell carcinoma cell lines and patient samples compared with normal adjacent tissues. We found overexpression of miR-143 in oral cancer cell lines suppresses cell migration, cellular glucose metabolism and proliferation...
February 7, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28151018/calcium-dobesilate-prevents-diabetic-kidney-disease-by-decreasing-bim-and-inhibiting-apoptosis-of-renal-proximal-tubular-epithelial-cells
#20
Tian Cai, Xiao-Yun Wu, Xiao-Qian Zhang, Hong-Xia Shang, Zhong-Wen Zhang, Jian-Jun Dong, Lin Liao
Apoptosis of renal proximal tubular epithelial cells (PTECs) plays a vital role in the pathogenesis and progression of diabetic kidney disease (DKD). Calcium dobesilate is a vascular protective compound used for treatment of diabetic retinopathy and chronic venous insufficiency. The aim of this study was to determine whether calcium dobesilate can protect PTECs from glucose-induced apoptosis and the potential mechanism of this effect. It is indicated that high glucose promoted abnormal apoptosis of HK2 cells, which was inhibited by treatment of calcium dobesilate, while Bim expression decreased in response to calcium dobesilate in high-glucose-treated HK2 cells...
February 2, 2017: DNA and Cell Biology
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