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https://www.readbyqxmd.com/read/29870900/targeted-reversal-and-phosphorescence-lifetime-imaging-of-cancer-cell-metabolism-via-a-theranostic-rhenium-i-dca-conjugate
#1
Jing Yang, Qian Cao, Hang Zhang, Liang Hao, Danxia Zhou, Zhenji Gan, Zhiwei Li, Ye-Xiang Tong, Liang-Nian Ji, Zong-Wan Mao
Cancer cell metabolism is quite different from normal cells. Targeting cancer metabolism and untuning the tumor metabolic machine has emerged as a promising strategy for cancer therapy. We have developed a multi-functional Re-dca conjugate (Re-dca 2) by conjugating the metabolic modulator dichloroacetate (DCA) to mitochondria-targeted rhenium(I) complex, allowing its efficient penetration into cancer cells and selective accumulation in mitochondria, thus achieving the cancer cell metabolism reversal from glycolysis to glucose oxidation at pharmacologically relevant DCA doses...
May 25, 2018: Biomaterials
https://www.readbyqxmd.com/read/29867151/protein-kinase-c%C3%AE%C2%B5-regulates-nuclear-translocation-of-extracellular-signal-regulated-kinase-which-contributes-to-bradykinin-induced-cyclooxygenase-2-expression
#2
Rei Nakano, Taku Kitanaka, Shinichi Namba, Nanako Kitanaka, Hiroshi Sugiya
The proinflammatory mediator bradykinin stimulated cyclooxygenase-2 (COX-2) expression and subsequently prostaglandin E2 synthesis in dermal fibroblasts. The involvement of B2 receptors and Gαq in the role of bradykinin was suggested by using pharmacological inhibitors. The PKC activator PMA stimulated COX-2 mRNA expression. Bradykinin failed to induce COX-2 mRNA expression in the presence of PKC inhibitors, whereas the effect of bradykinin was observed in the absence of extracellular Ca2+ . Bradykinin-induced COX-2 mRNA expression was inhibited in cells transfected with PKCε siRNA...
June 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29864662/chronic-exposure-to-triadimenol-at-environmentally-relevant-concentration-adversely-affects-aging-biomarkers-in-caenorhabditis-elegans-associated-with-insulin-igf-1-signaling-pathway
#3
Chun Ming How, Shang-Wei Li, Vivian Hsiu-Chuan Liao
Triadimenol, an agricultural fungicide, is an emerging environmental concern due to its wide usage, detection in the environment, and its chemical persistency. Triadimenol has been found to disrupt endocrine signaling and alter function of several transcription factors, yet its age-related toxicity effects remain unclear. This study used Caenorhabditis elegans as an in vivo model organism to elucidate the age-related effects of triadimenol and its underlying mechanisms. The results showed that chronic exposure to triadimenol at environmentally relevant concentrations (3, 30, and 300 μg/L) adversely affected several toxicity endpoints including growth, total brood size, and locomotive behaviors...
June 1, 2018: Science of the Total Environment
https://www.readbyqxmd.com/read/29788890/inhibition-of-pyruvate-dehydrogenase-kinase-as-a-therapeutic-strategy-against-cancer
#4
Swatishree Sradhanjali, Mamatha M Reddy
Cancer cells alter their metabolism to support the uninterrupted supply of biosynthetic molecules required for continuous proliferation. Glucose metabolism is frequently reprogrammed in several tumors in addition to fatty acid, amino acid and glutamine metabolism. Pyruvate dehydrogenase kinase (PDK) is a gatekeeper enzyme involved in altered glucose metabolism in tumors. There are four isoforms of PDK (1 to 4) in humans. PDK phosphorylates E1α subunit of pyruvate dehydrogenase complex (PDC) and inactivates it...
May 22, 2018: Current Topics in Medicinal Chemistry
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
#5
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/29739849/a-novel-inhibitor-of-pyruvate-dehydrogenase-kinase-stimulates-myocardial-carbohydrate-oxidation-in-diet-induced-obesity
#6
Cheng-Yang Wu, Santhosh Satapati, Wenjun Gui, Richard M Wynn, Gaurav Sharma, Mingliang Lou, Xiangbing Qi, Shawn C Burgess, Craig Malloy, Chalermchai Khemtong, A Dean Sherry, David Chuang, Matthew E Merritt
The pyruvate dehydrogenase complex (PDC) is a key control point of energy metabolism and is subject to regulation by multiple mechanisms, including post-translational phosphorylation by pyruvate dehydrogenase kinase (PDK). Pharmacological modulation of PDC activity could provide a new treatment for diabetic cardiomyopathy, as dysregulated substrate selection is concomitant with decreased heart function. Dichloroacetate (DCA), a classic PDK inhibitor, has been used to treat diabetic cardiomyopathy, but the lack of specificity and side effects of DCA indicate a more specific inhibitor of PDK is needed...
May 8, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29733959/itraq-based-proteomic-profile-analysis-of-isknv-infected-cpb-cells-with-emphasizing-on-glucose-metabolism-apoptosis-and-autophagy-pathways
#7
Shiwei Wu, Lujun Yu, Xiaozhe Fu, Xi Yan, Qiang Lin, Lihui Liu, Hongru Liang, Ningqiu Li
Infectious spleen and kidney necrosis virus (ISKNV) has caused significant losses in the cultured mandarin fish (Siniperca chuatsi) industry. The molecular mechanisms that underlie interaction between ISKNV and hosts are not fully understood. In this study, the proteomic profile of CPB cells at progressive time points after ISKNV infection was analyzed by isobaric tags for relative and absolute quantitation (iTRAQ). A total of 2731 proteins corresponding to 6363 novel peptides (false discovery rate <0.01) were identified...
May 4, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29656110/targeting-hepatic-pyruvate-dehydrogenase-kinases-restores-insulin-signaling-and-mitigates-chrebp-mediated-lipogenesis-in-diet-induced-obese-mice
#8
Cheng-Yang Wu, Shih-Chia Tso, Jacinta L Chuang, Wen-Jun Gui, Mingliang Lou, Gaurav Sharma, Chalermchai Khemtong, Xiangbing Qi, R Max Wynn, David T Chuang
OBJECTIVE: Mitochondrial pyruvate dehydrogenase kinases 1-4 (PDKs1-4) negatively regulate activity of the pyruvate dehydrogenase complex (PDC) by reversible phosphorylation. PDKs play a pivotal role in maintaining energy homeostasis and contribute to metabolic flexibility by attenuating PDC activity in various mammalian tissues. Cumulative evidence has shown that the up-regulation of PDK4 expression is tightly associated with obesity and diabetes. In this investigation, we test the central hypothesis that PDKs1-4 are a pharmacological target for lowering glucose levels and restoring insulin sensitivity in obesity and type 2 diabetes (T2D)...
June 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29653124/doxorubicin-triggers-bioenergetic-failure-and-p53-activation-in-mouse-stem-cell-derived-cardiomyocytes
#9
Teresa Cunha-Oliveira, Luciana L Ferreira, Ana Raquel Coelho, Cláudia M Deus, Paulo J Oliveira
Doxorubicin (DOX) is a widely used anticancer drug that could be even more effective if its clinical dosage was not limited because of delayed cardiotoxicity. Beating stem cell-derived cardiomyocytes are a preferred in vitro model to further uncover the mechanisms of DOX-induced cardiotoxicity. Our objective was to use cultured induced-pluripotent stem cell(iPSC)-derived mouse cardiomyocytes (Cor.At) to investigate the effects of DOX on cell and mitochondrial metabolism, as well as on stress responses. Non-proliferating and beating Cor...
June 1, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29615678/protein-bound-nad-p-h-lifetime-is-sensitive-to-multiple-fates-of-glucose-carbon
#10
Joe T Sharick, Peter F Favreau, Amani A Gillette, Sophia M Sdao, Matthew J Merrins, Melissa C Skala
While NAD(P)H fluorescence lifetime imaging (FLIM) can detect changes in flux through the TCA cycle and electron transport chain (ETC), it remains unclear whether NAD(P)H FLIM is sensitive to other potential fates of glucose. Glucose carbon can be diverted from mitochondria by the pentose phosphate pathway (via glucose 6-phosphate dehydrogenase, G6PDH), lactate production (via lactate dehydrogenase, LDH), and rejection of carbon from the TCA cycle (via pyruvate dehydrogenase kinase, PDK), all of which can be upregulated in cancer cells...
April 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29593636/combined-treatment-with-dichloroacetic-acid-and-pyruvate-reduces-hippocampal-neuronal-death-after-transient-cerebral-ischemia
#11
Dae Ki Hong, A Ra Kho, Bo Young Choi, Song Hee Lee, Jeong Hyun Jeong, Sang Hwon Lee, Kyoung-Ha Park, Jae-Bong Park, Sang Won Suh
Transient cerebral ischemia (TCI) occurs when blood flow to the brain is ceased or dramatically reduced. TCI causes energy depletion and oxidative stress, which leads to neuronal death and cognitive impairment. Dichloroacetic acid (DCA) acts as an inhibitor of pyruvate dehydrogenase kinase (PDK). Additionally, DCA is known to increase mitochondrial pyruvate uptake and promotes glucose oxidation during glycolysis, thus enhancing pyruvate dehydrogenase (PDH) activity. In this study, we investigated whether the inhibition of PDK activity by DCA, which increases the rate of pyruvate conversion to adenosine triphosphate (ATP), prevents ischemia-induced neuronal death...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29535262/skp2-dependent-reactivation-of-akt-drives-resistance-to-pi3k-inhibitors
#12
Emilie Clement, Hiroyuki Inuzuka, Naoe T Nihira, Wenyi Wei, Alex Toker
The PI3K-AKT kinase signaling pathway is frequently deregulated in human cancers, particularly breast cancer, where amplification and somatic mutations of PIK3CA occur with high frequency in patients. Numerous small-molecule inhibitors targeting both PI3K and AKT are under clinical evaluation, but dose-limiting toxicities and the emergence of resistance limit therapeutic efficacy. Various resistance mechanisms to PI3K inhibitors have been identified, including de novo mutations, feedback activation of AKT, or cross-talk pathways...
March 13, 2018: Science Signaling
https://www.readbyqxmd.com/read/29527004/microrna-155-positively-regulates-glucose-metabolism-via-pik3r1-foxo3a-cmyc-axis-in-breast-cancer
#13
Sinae Kim, Eunji Lee, Jaeyun Jung, Jong Won Lee, Hee Jung Kim, Jisun Kim, Hyun Ju Yoo, Hee Jin Lee, Sun Young Chae, Sang Min Jeon, Byung Ho Son, Gyungyup Gong, Shyam K Sharan, Suhwan Chang
MicroRNA is an endogenous, small RNA controlling multiple target genes and playing roles in various biological processes including tumorigenesis. Here, we addressed the function of miR-155 using LC-MS/MS-based metabolic profiling of miR-155 deficient breast cancer cells. Our results revealed the loss of miR-155 hampers glucose uptake and glycolysis, via the down-regulation of glucose transporters and metabolic enzymes including HK2, PKM2, and LDHA. We showed this is due to the down-regulation of cMYC, controlled through phosphoinositide-3-kinase regulatory subunit alpha (PIK3R1)-PDK1/AKT-FOXO3a pathway...
March 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29482638/investigation-of-hypoxia-networks-in-ovarian-cancer-via-bioinformatics-analysis
#14
Ke Zhang, Xiangjun Kong, Guangde Feng, Wei Xiang, Long Chen, Fang Yang, Chunyu Cao, Yifei Ding, Hang Chen, Mingxing Chu, Pingqing Wang, Baoyun Zhang
BACKGROUND: Ovarian cancer is a leading cause of the death from gynecologic malignancies. Hypoxia is closely related to the malignant growth of cells. However, the molecular mechanism of hypoxia-regulated ovarian cancer cells remains unclear. Thus, this study was conducted to identify the key genes and pathways implicated in the regulation of hypoxia by bioinformatics analysis. METHODS: Using the datasets of GSE53012 downloaded from the Gene Expression Omnibus (GEO), the differentially expressed genes (DEGs) were screened by comparing the RNA expression from cycling hypoxia group, chronic hypoxia group, and control group...
February 26, 2018: Journal of Ovarian Research
https://www.readbyqxmd.com/read/29471628/activation-of-pyruvate-dehydrogenase-by-sodium-dichloroacetate-shifts-metabolic-consumption-from-amino-acids-to-glucose-in-ipec-j2-cells-and-intestinal-bacteria-in-pigs
#15
Rui An, Zhiru Tang, Yunxia Li, Tiejun Li, Qingqing Xu, Jifu Zhen, Feiru Huang, Jing Yang, Cheng Chen, Zhaoliang Wu, Mao Li, Jiajing Sun, Xiangxin Zhang, Jinchao Chen, Liuting Wu, Shengjun Zhao, Jiang Qingyan, Weiyun Zhu, Yulong Yin, Zhihong Sun
The extensive metabolism of amino acids (AA) as fuel is an important reason for the low use efficiency of protein in pigs. In this study, we investigated whether regulation of the pyruvate dehydrogenase kinase (PDK)/pyruvate dehydrogenase alpha 1 (PDHA1) pathway affected AA consumption by porcine intestinal epithelial (IPEC-J2) cells and intestinal bacteria in pigs. The effects of knockdown of PDHA1 and PDK1 with small interfering RNA (siRNA) on nutrient consumption by IPEC-J2 cells were evaluated. IPEC-J2 cells were then cultured with sodium dichloroacetate (DCA) to quantify AA and glucose consumption and nutrient oxidative metabolism...
April 18, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29459421/igf-1-protects-sh-sy5y-cells-against-mpp-induced-apoptosis-via-pi3k-pdk-1-akt-pathway
#16
Chanyang Kim, Seungjoon Park
Insulin-like growth factor (IGF)-1 is a well-known anti-apoptotic pro-survival factor and phosphatidylinositol-3-kinase (PI3K)/Akt pathway is linked to cell survival induced by IGF-1. It is also reported that Akt signaling is modulated by 3-phosphoinositide-dependent kinase-1 (PDK1). In the current study, we investigated whether the anti-apoptotic effect of IGF-1 in SH-SY5Y cells exposed to 1-methyl-4-phenylpyridinium (MPP+ ) is associated with the activity of PI3K/PDK1/Akt pathway. Treatment of cells with IGF-1 inhibited MPP+ -induced apoptotic cell death...
March 2018: Endocrine Connections
https://www.readbyqxmd.com/read/29456710/mechanism-of-apoptosis-induction-associated-with-erk1-2-upregulation-via-goniothalamin-in-melanoma-cells
#17
Suphakorn Tangchirakhaphan, Sukanda Innajak, Sirinun Nilwarangkoon, Nudjaree Tanjapatkul, Wilawan Mahabusrakum, Ramida Watanapokasin
The present study aimed to investigate the effect of goniothalamin on apoptosis induction in the A375 melanoma cell line. Melanoma is a type of skin cancer with increased prevalence and no potential standard treatment. Goniothalamin is a plant, bioactive styrly-lactone, which has various bioactivities including anti-microbial, anti-inflammatory and anti-cancer. Apoptosis induction by goniothalamin has been studied in numerous cancer cell lines, however not in the melanoma cell line A375. The results of the MTT assay demonstrated that goniothalamin induced anti-proliferation in a dose dependent manner...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29406780/acute-activation-of-pyruvate-dehydrogenase-increases-glucose-oxidation-in-muscle-without-changing-glucose-uptake
#18
Lewin Small, Amanda E Brandon, Lake-Ee Quek, James R Krycer, David E James, Nigel Turner, Gregory J Cooney
Pyruvate dehydrogenase (PDH) activity is a key component of the glucose/fatty acid cycle hypothesis for the regulation of glucose uptake and metabolism. We have investigated whether acute activation of PDH in muscle can alleviate the insulin resistance caused by feeding animals a high fat diet. The importance of PDH activity in muscle glucose disposal under insulin-stimulated conditions was determined by infusing the pyruvate dehydrogenase kinase (PDK) inhibitor dichloroacetate (DCA) into high fat diet-fed (HFD) Wistar rats during a hyperinsulinemic-euglycemic clamp...
February 6, 2018: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29243067/translational-regulation-in-the-anoxic-turtle-trachemys-scripta-elegans
#19
Kama E Szereszewski, Kenneth B Storey
The red-eared slider turtle (Trachemys scripta elegans), has developed remarkable adaptive mechanisms for coping with decreased oxygen availability during winter when lakes and ponds become covered with ice. Strategies for enduring anoxia tolerance include an increase in fermentable fuel reserves to support anaerobic glycolysis, the buffering of end products to minimize acidosis, altered expression in crucial survival genes, and strong metabolic rate suppression to minimize ATP-expensive metabolic processes such as protein synthesis...
December 14, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29191981/impact-of-training-state-on-fasting-induced-regulation-of-adipose-tissue-metabolism-in-humans
#20
Lærke Bertholdt, Anders Gudiksen, Tomasz Stankiewicz, Ida Villesen, Jonas Tybirk, Gerrit van Hall, Jens Bangsbo, Peter Plomgaard, Henriette Pilegaard
Recruitment of fatty acids from adipose tissue is increased during fasting. However, the molecular mechanisms behind fasting-induced metabolic regulation in human adipose tissue and the potential impact of training state in this are unknown. Therefore the aim of the present study was to investigate 1) fasting-induced regulation of lipolysis and glyceroneogenesis in human adipose tissue as well as 2) the impact of training state on basal oxidative capacity and fasting-induced metabolic regulation in human adipose tissue...
March 1, 2018: Journal of Applied Physiology
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