keyword
MENU ▼
Read by QxMD icon Read
search

Pdk

keyword
https://www.readbyqxmd.com/read/28423362/trop2-promotes-proliferation-migration-and-metastasis-of-gallbladder-cancer-cells-by-regulating-pi3k-akt-pathway-and-inducing-emt
#1
Xinxing Li, Shifeng Teng, Yanyan Zhang, Weigang Zhang, Xianwen Zhang, Kai Xu, Houshan Yao, Jun Yao, Haolu Wang, Xiaowen Liang, Zhiqian Hu
The human trophoblast cell surface antigen 2 (TROP2) is overexpressed in many cancers. However, its effect on proliferation, migration and metastasis of gallbladder cancer remains unclear. In this study, we found that TROP2 was highly expressed in gallbladder cancer. Overexpression of TROP2 was associated with poor prognosis. Knockdown of TROP2 in gallbladder cancer cell lines strongly inhibited the cell proliferation, clone formation, invasion and migration in vitro, while TROP2 overexpression had opposite effects...
April 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414314/cell-competition-with-normal-epithelial-cells-promotes-apical-extrusion-of-transformed-cells-through-metabolic%C3%A2-changes
#2
Shunsuke Kon, Kojiro Ishibashi, Hiroto Katoh, Sho Kitamoto, Takanobu Shirai, Shinya Tanaka, Mihoko Kajita, Susumu Ishikawa, Hajime Yamauchi, Yuta Yako, Tomoko Kamasaki, Tomohiro Matsumoto, Hirotaka Watanabe, Riku Egami, Ayana Sasaki, Atsuko Nishikawa, Ikumi Kameda, Takeshi Maruyama, Rika Narumi, Tomoko Morita, Yoshiteru Sasaki, Ryosuke Enoki, Sato Honma, Hiromi Imamura, Masanobu Oshima, Tomoyoshi Soga, Jun-Ichi Miyazaki, Michael R Duchen, Jin-Min Nam, Yasuhito Onodera, Shingo Yoshioka, Junichi Kikuta, Masaru Ishii, Masamichi Imajo, Eisuke Nishida, Yoichiro Fujioka, Yusuke Ohba, Toshiro Sato, Yasuyuki Fujita
Recent studies have revealed that newly emerging transformed cells are often apically extruded from epithelial tissues. During this process, normal epithelial cells can recognize and actively eliminate transformed cells, a process called epithelial defence against cancer (EDAC). Here, we show that mitochondrial membrane potential is diminished in RasV12-transformed cells when they are surrounded by normal cells. In addition, glucose uptake is elevated, leading to higher lactate production. The mitochondrial dysfunction is driven by upregulation of pyruvate dehydrogenase kinase 4 (PDK4), which positively regulates elimination of RasV12-transformed cells...
April 17, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28405929/thermodynamics-in-cancers-opposing-interactions-between-ppar-gamma-and-the-canonical-wnt-beta-catenin-pathway
#3
REVIEW
Yves Lecarpentier, Victor Claes, Alexandre Vallée, Jean-Louis Hébert
Cancer cells are the site of numerous metabolic and thermodynamic abnormalities. We focus this review on the interactions between the canonical WNT/beta-catenin pathway and peroxisome proliferator-activated receptor gamma (PPAR gamma) in cancers and their implications from an energetic and metabolic point of view. In numerous tissues, PPAR gamma activation induces inhibition of beta-catenin pathway, while the activation of the canonical WNT/beta-catenin pathway inactivates PPAR gamma. In most cancers but not all, PPAR gamma is downregulated while the WNT/beta-catenin pathway is upregulated...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28395173/particular-phosphorylation-of-pi3k-akt-on-thr308-via-pdk-1-and-pten-mediates-melatonin-s-neuroprotective-activity-after-focal-cerebral-ischemia-in-mice
#4
Ulkan Kilic, Ahmet Burak Caglayan, Mustafa Caglar Beker, Mehmet Yalcin Gunal, Berrak Caglayan, Esra Yalcin, Taha Kelestemur, Reyhan Zeynep Gundogdu, Burak Yulug, Bayram Yılmaz, Bilal Ersen Kerman, Ertugrul Kilic
Apart from its potent antioxidant property, recent studies have revealed that melatonin promotes PI3K/Akt phosphorylation following focal cerebral ischemia (FCI) in mice. However, it is not clear (i) whether increased PI3K/Akt phosphorylation is a concomitant event or it directly contributes to melatonin's neuroprotective effect, and (ii) how melatonin regulates PI3K/Akt signaling pathway after FCI. In this study, we showed that Akt was intensively phosphorylated at the Thr308 activation loop as compared with Ser473 by melatonin after FCI...
April 5, 2017: Redox Biology
https://www.readbyqxmd.com/read/28371849/therapeutic-inhibition-of-mir-375-attenuates-post-mi-inflammatory-response-and-left-ventricular-dysfunction-via-pdk-1-akt-signaling-axis
#5
Venkata Naga Srikanth Garikipati, Suresh Kumar Verma, Darukeshwara Jolardarashi, Zhongjian Cheng, Jessica Ibetti, Maria Cimini, Yan Tang, Mohsin Khan, Yujia Yue, Cindy Benedict, Emily Nickoloff, May M Trungcao, Erhe Gao, Prasanna Krishnamurthy, David A Goukassian, Walter J Koch, Raj Kishore
Aims: Increased miR-375 levels has been implicated in rodent models of myocardial infarction (MI) and with patients with heart failure. However, no prior study had established a therapeutic role of miR-375 in ischemic myocardium. Therefore, we assessed whether inhibition of MI-induced miR-375 by LNA anti-miR -375 can improve recovery after acute MI. Methods and Results: Ten weeks old mice were treated with either control or LNA anti miR-375 after induction of MI by LAD ligation...
March 28, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28367092/pkd-knockdown-inhibits-pressure-overload-induced-cardiac-hypertrophy-by-promoting-autophagy-via-akt-mtor-pathway
#6
Di Zhao, Wei Wang, Hao Wang, Honghai Peng, Xiangjuan Liu, Weixing Guo, Guohai Su, Zhuo Zhao
Growing evidence shows that protein kinase D (PKD) plays an important role in the development of pressure overload-induced cardiac hypertrophy. However, the mechanisms involved are not clear. This study tested our hypothesis that PKD might mediate cardiac hypertrophy by negatively regulating autophagy using the technique of PKD knockdown by siRNA. Cardiac hypertrophy was induced in 8-week old male C57BL/6 mice by transverse aortic constriction (TAC). TAC mice were then divided into five groups receiving the treatments of vehicle (DMSO), an autophagy inducer rapamycin (1 mg/kg/day, i...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28366735/regulator-of-g-protein-signaling-1-modulates-paraquat-induced-oxidative-stress-and-longevity-via-the-insulin-like-signaling-pathway-in-caenorhabditis-elegans
#7
Mingyu Wu, Xin Kang, Qiang Wang, Chunyu Zhou, Chandra Mohan, Ai Peng
Insulin or insulin like signaling (IIS) pathway is a crucial pathway in Caenorhabditis elegans associated with mediating longevity, and stress resistance. Regulators of G protein signaling (RGS) also modulate stress resistance and longevity in multiple in vitro and in vivo models. However, the mechanism underlying RGS mediating stress resistance and longevity remains largely unclear. Here we report that rgs-1, an important member of rgs family, is a novel modulator of IIS pathway in C. elegans. We found that the loss of rgs-1 dramatically promoted paraquat resistance in C...
March 31, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28287848/immunomodulating-and-immunoresistance-properties-of-cancer-initiating-cells-implications-for-the-clinical-success-of-immunotherapy
#8
REVIEW
Cristina Maccalli, Giorgio Parmiani, Soldano Ferrone
Cancer-initiating cells (CICs) represent a relatively rare subpopulation of cells endowed with self-renewal, stemness properties, tumorigenicity in immunodeficient mice, and resistance to standard therapies as well as to immunotherapy. Here, we review the biological and immunological characteristics of CICs with special focus on the immunomodulating mechanisms they utilize to escape from immunosurveillance. The recently developed immunotherapeutic strategies have yielded remarkable clinical results in many types of tumors, indicating that indeed a patient's immune system can mount an immune response, which is effective in controlling tumor growth...
April 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28238857/asiaticoside-attenuation-of-rotenone-induced-oxidative-burden-in-a-rat-model-of-hemiparkinsonism-by-maintaining-the-phosphoinositide-mediated-synaptic-integrity
#9
Margabandhu Gopi, Vanisree Arambakkam Janardhanam
Asiaticoside (AS), a triterpenoid saponin isolated from the Indian medicinal herb Centella asiatica is known to exert a neuroprotective effect by attenuating the neurobehavioral, neurochemical and pathological changes in animal models. However, its potential neuroprotection in rotenone-induced hemiparkinsonism which implicates phospholipid-mediated neurotransmission remains unclear. Therefore, we have investigated the neuroprotective effects of AS in rat model of ROT-infused hemiparkinsonism with respect to phosphoinositides-assisted cytodynamics and synaptic function...
February 24, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28230160/global-view-of-cognate-kinase-activation-by-the-human-pyruvate-dehydrogenase-complex
#10
Elena L Guevara, Luying Yang, Barbara Birkaya, Jieyu Zhou, Natalia S Nemeria, Mulchand S Patel, Frank Jordan
The human pyruvate dehydrogenase complex (PDC) comprises four multidomain components, E1, E3, E2 and an E3-binding protein (E3BP), the latter two forming the core as E2·E3BP sub-complex. Pyruvate flux through PDC is regulated via phosphorylation (inactivation) at E1 by four PDC kinases (PDKs), and reactivation by two PDC phosphatases. Up-regulation of PDK isoform gene expression is reported in several forms of cancer, while PDKs may be further activated by PDC by binding to the E2·E3BP core. Hence, the PDK: E2·E3BP interaction provides new therapeutic targets...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28208156/oncogenic-role-of-pdk4-in-human-colon-cancer-cells
#11
D Leclerc, D N T Pham, N Lévesque, M Truongcao, W D Foulkes, C Sapienza, R Rozen
BACKGROUND: Cancer cells maintain high rates of glycolysis. Pyruvate dehydrogenase kinases (PDK) contribute to this phenomenon, which favours apoptosis resistance and cellular transformation. We previously reported upregulation of PDK4 in normal mucosa of colorectal cancer (CRC) patients compared with controls and in preneoplastic intestine of our mouse model. Decreased methylation of four consecutive PDK4 CpGs was observed in normal mucosa of patients. Although other members of the PDK family have been investigated for transformation potential, PDK4 has not been extensively studied...
March 28, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28182733/pyruvate-dehydrogenase-kinase-1-is-essential-for-transplantable-mouse-bone-marrow-hematopoietic-stem-cell-and-progenitor-function
#12
Camilla Halvarsson, Pernilla Eliasson, Jan-Ingvar Jönsson
BACKGROUND: Accumulating evidence suggests that hypoxic areas in the bone marrow are crucial for maintenance of hematopoietic stem cells (HSCs) by supporting a quiescent state of cell cycle and regulating the transplantation capacity of long-term (LT)-HSCs. In addition, HSCs seem to express a metabolic profile of energy production away from mitochondrial oxidative phosphorylation in favor of glycolysis. At oxygen deprivation, hypoxia inducible factor 1α (HIF-1α) is known to induce glycolytic enzymes as well as suppressing mitochondrial energy production by inducing pyruvate dehydrogenase kinase 1 (Pdk1) in most cell types...
2017: PloS One
https://www.readbyqxmd.com/read/28163304/predominant-contribution-of-dgk%C3%AE-over-dgk%C3%AE-in-the-control-of-pkc-pdk-1-regulated-functions-in-t-cells
#13
Antonia Ávila-Flores, Javier Arranz-Nicolás, Elena Andrada, Denise Soutar, Isabel Mérida
Diacylglycerol kinase (DGK)-mediated consumption of the diacylglycerol (DAG) generated in response to antigen recognition is an important mechanism to limit T-cell function. Targeting DGK activity presents new opportunities for therapeutic manipulation of the immune response, but assessment of individual DGK functions is complex. T cells express two DGK isoforms, DGKα and DGKζ, and there are no isoform-specific inhibitors. Here we used short interfering RNA-mediated gene silencing in human T cells and DGKα- and DGKζ-deficient mice to define DGK isoform-specific regulation of key signaling pathways during T-cell activation...
February 28, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28163135/a-mechanism-based-pharmacokinetic-enzyme-turnover-model-for-dichloroacetic-acid-autoinhibition-in-rats
#14
Yu Jiang, Gary Milavetz, Margaret O James, Guohua An
Dichloroacetic acid (DCA), a halogenated organic acid, is a pyruvate dehydrogenase kinase inhibitor that has been used to treat congenital or acquired lactic acidosis and is currently in early-phase clinical trials for cancer treatment. DCA was found to inhibit its own metabolism by irreversibly inactivating glutathione transferase zeta 1 (GSTZ1-1), resulting in nonlinear kinetics and abnormally high accumulation ratio after repeated dosing. In this analysis, a semi-mechanistic pharmacokinetic enzyme turnover model was developed for the first time to capture DCA autoinhibition, gastrointestinal region-dependent absorption, and time-dependent change in bioavailability in rats...
February 3, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28123081/histone-deacetylase-inhibitors-protect-against-pyruvate-dehydrogenase-dysfunction-in-huntington-s-disease
#15
Luana Naia, Teresa Cunha-Oliveira, Joana Rodrigues, Tatiana R Rosenstock, Ana Oliveira, Márcio Ribeiro, Catarina Carmo, Sofia I Oliveira-Sousa, Ana I Duarte, Michael R Hayden, A Cristina Rego
Transcriptional deregulation and changes in mitochondrial bioenergetics, including pyruvate dehydrogenase (PDH) dysfunction, have been described in Huntington's disease (HD). We previously showed that histone deacetylase inhibitors (HDACi), trichostatin A and sodium butyrate (SB), ameliorate mitochondrial function in cells expressing mutant huntingtin. In this work we investigated the effect of HDACi on regulation of PDH activity in striatal cells derived from HD knock-in mice and YAC128 mice. Mutant cells exhibited decreased PDH activity and increased PDH E1alpha phosphorylation/inactivation, accompanied by enhanced protein levels of PDH kinases (PDK)1/3...
January 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28109078/3-phosphoinositide-dependent-protein-kinase-1-pdk-1-promotes-migration-and-invasion-in-gastric-cancer-cells-through-activating-the-nf-%C3%AE%C2%BAb-pathway
#16
Ning Wu, Changyu He, Bohui Zhu, Jinling Jiang, Yiwen Chen, Tao Ma
Gastric cancer (GC) is one of the most common cancers and the second leading cause of cancer deaths in the world. Manyfactors were reported involving the progression and development of GC. In this study, we aimed to investigate the correlation of 3-phosphoinositide dependent protein kinase 1 (PDK-1) with cell viability, cell migration, and cell invasion of GC. The expression of PDK-1 was measured in different GC cell lines. Thereafter, the expression of PDK-1 was interfered by small hairpin RNA (shRNA) and then incubated with or without the inhibitor of NF-κB pyrrolidine dithiocarbamate (PDTC)...
January 20, 2017: Oncology Research
https://www.readbyqxmd.com/read/28094552/glucose-metabolism-in-cancer-and-ischemia-possible-therapeutic-consequences-of-the-warburg-effect
#17
Spela Salamon, Eva Podbregar, Peter Kubatka, Dietrich Büsselberg, Martin Caprnda, Radka Opatrilova, Vanda Valentova, Mariusz Adamek, Peter Kruzliak, Matej Podbregar
The Warburg effect states that the main source of energy for cancer cells is not aerobic respiration, but glycolysis-even in normoxia. The shift from one to the other is governed by mutually counteracting enzymes: pyruvate dehydrogenase and pyruvate dehydrogenase kinase (PDK). Anaerobic metabolism of cancer cells promotes cell proliferation, local tissue immunosuppression, resistance to hypoxic conditions, and metastatic processes. By switching glucose back to oxidative metabolism, these effects might be reversed...
February 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28093038/metabonomic-strategy-for-the-evaluation-of-chinese-medicine-salvia-miltiorrhiza-and-dalbergia-odorifera-interfering-with-myocardial-ischemia-reperfusion-injury-in-rats
#18
Fei Mu, Jialin Duan, Haixu Bian, Xiaohu Zhai, Peijin Shang, Rui Lin, Meina Zhao, Dongmei Hu, Ying Yin, Aidong Wen, Miaomiao Xi
Extract of Salvia miltiorrhiza and Dalbergia Odorifera (SM-DOO) has been traditionally used for the prevention and treatment of cardiovascular diseases. However, information regarding the pharmacodyamic material basis and potential mechanism remain unknown. Male Sprague-Dawley rats were divided into four groups: Sham, Model, Diltiazem, and SM-DOO group, n = 6. Rats were pretreated with homologous drugs for 7 days, and then subjected to 30 minutes of ischemia followed by 180 minutes of reperfusion. Cardioprotection effects of SM-DOO on myocardial ischemia/reperfusion (MI/R) injury rats were examined by hemodynamics, infarct area, histopathology, biochemical indicators, and Western blot analysis...
March 7, 2017: Rejuvenation Research
https://www.readbyqxmd.com/read/28040265/pyruvate-dehydrogenase-kinase-4-deficiency-attenuates-cisplatin-induced-acute-kidney-injury
#19
Chang Joo Oh, Chae-Myeong Ha, Young-Keun Choi, Sungmi Park, Mi Sun Choe, Nam Ho Jeoung, Yang Hoon Huh, Hyo-Jeong Kim, Hee-Seok Kweon, Ji-Min Lee, Sun Joo Lee, Jae-Han Jeon, Robert A Harris, Keun-Gyu Park, In-Kyu Lee
Clinical prescription of cisplatin, one of the most widely used chemotherapeutic agents, is limited by its side effects, particularly tubular injury-associated nephrotoxicity. Since details of the underlying mechanisms are not fully understood, we investigated the role of pyruvate dehydrogenase kinase (PDK) in cisplatin-induced acute kidney injury. Among the PDK isoforms, PDK4 mRNA and protein levels were markedly increased in the kidneys of mice treated with cisplatin, and c-Jun N-terminal kinase activation was involved in cisplatin-induced renal PDK4 expression...
December 28, 2016: Kidney International
https://www.readbyqxmd.com/read/28035937/mtorc2-rictor-in-alzheimer-s-disease-and-reversal-of-amyloid-%C3%AE-expression-induced-insulin-resistance-and-toxicity-in-rat-primary-cortical-neurons
#20
Han-Kyu Lee, Bumsup Kwon, Cynthia A Lemere, Suzanne de la Monte, Kyohei Itamura, Austin Y Ha, Henry W Querfurth
Mammalian target of rapamycin complex 1 (mTORC1), a nutrient sensor and central controller of cell growth and proliferation, is altered in various models of Alzheimer's disease (AD). Even less studied or understood in AD is mammalian target of rapamycin complex 2 (mTORC2) that influences cellular metabolism, in part through the regulations of Akt/PKB and SGK. Dysregulation of insulin/PI3K/Akt signaling is another important feature of AD pathogenesis. We found that both total mTORC1 and C2 protein levels and individual C1 and C2 enzymatic activities were decreased in human AD brain samples...
December 30, 2016: Journal of Alzheimer's Disease: JAD
keyword
keyword
31654
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"