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https://www.readbyqxmd.com/read/28542136/pak4-regulates-g6pd-activity-by-p53-degradation-involving-colon-cancer-cell-growth
#1
Xiumei Zhang, Xia Zhang, Yang Li, Yangguang Shao, Jianying Xiao, Ge Zhu, Feng Li
The p21-activated kinase 4 (PAK4) is overexpressed in different cancers and promotes proliferation of cancer cells. Reprogramming of glucose metabolism is found in most cancer cells which in turn supports rapid proliferation. However, the relationship between PAK4 and glucose metabolism in cancer cells has not been explored. In this study, we reported that PAK4 promoted glucose intake, NADPH production and lipid biosynthesis, leading to an increased proliferation of colon cancer cells. Mechanistically, PAK4 interacted with glucose-6-phosphate dehydrogenase (G6PD), a rate-limiting enzyme of the pentose phosphate pathway and increased G6PD activity via enhancing Mdm2-mediated p53 ubiquitination degradation...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28533555/scopolin-ameliorates-high-fat-diet-induced-hepatic-steatosis-in-mice-potential-involvement-of-sirt1-mediated-signaling-cascades-in-the-liver
#2
Ahyoung Yoo, Vikram P Narayan, Eun Young Hong, Wan Kyunn Whang, Taesun Park
The present study aimed to investigate whether scopolin exhibits beneficial effects on high-fat diet (HFD)-induced hepatic steatosis in mice. The involvement of sirtuin 1 (SIRT1) as a molecular target for scopolin was also explored. Scopolin decreased the Km of SIRT1 for p53 and nicotinamide adenine dinucleotide without altering Vmax in a cell-free system. Scopolin alleviated oleic acid-induced lipid accumulation and downregulation of SIRT1 activity in HepG2 cells, and these beneficial effects of scopolin were abolished in the presence of SIRT1 inhibitor...
May 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28514055/caveolin-1-deficiency-induces-premature-senescence-with-mitochondrial-dysfunction
#3
Dong-Min Yu, Seung Hee Jung, Hyoung-Tae An, Sungsoo Lee, Jin Hong, Jun Sub Park, Hyun Lee, Hwayeon Lee, Myeong-Suk Bahn, Hyung Chul Lee, Na-Kyung Han, Jesang Ko, Jae-Seon Lee, Young-Gyu Ko
Paradoxical observations have been made regarding the role of caveolin-1 (Cav-1) during cellular senescence. For example, caveolin-1 deficiency prevents reactive oxygen species-induced cellular senescence despite mitochondrial dysfunction, which leads to senescence. To resolve this paradox, we re-addressed the role of caveolin-1 in cellular senescence in human diploid fibroblasts, A549, HCT116, and Cav-1(-/-) mouse embryonic fibroblasts. Cav-1 deficiency (knockout or knockdown) induced cellular senescence via a p53-p21-dependent pathway, downregulating the expression level of the cardiolipin biosynthesis enzymes and then reducing the content of cardiolipin, a critical lipid for mitochondrial respiration...
May 17, 2017: Aging Cell
https://www.readbyqxmd.com/read/28505155/oxidative-stress-and-expression-of-insulin-signaling-proteins-in-the-brain-of-diabetic-rats-role-of-nigella-sativa-oil-and-antidiabetic-drugs
#4
Mahmoud Balbaa, Shaymaa A Abdulmalek, Sofia Khalil
BACKGROUND AND OBJECTIVES: Insulin resistance of the brain is a specific form of type2-diabetes mellitus (T2DM) and the active insulin-signaling pathway plays a neuroprotective role against damaging conditions and Alzheimer's progression. The present study identifies the mediated emerging effects of the Nigella sativa oil (NSO) on the memory enhancing process, its anti-oxidative, acetylcholinestrase (AChE) inhibition, anti-brain insulin resistance and anti-amyloidogenic activities. In addition, the possible role of some anti-diabetic drugs in the neuro-protection processes and their effect in combination with NSO and/or the insulin receptor inhibitor IOMe-AG538 were investigated...
2017: PloS One
https://www.readbyqxmd.com/read/28496125/enhancing-specific-disruption-of-intracellular-protein-complexes-by-hydrocarbon-stapled-peptides-using-lipid-based-delivery
#5
D Thean, J S Ebo, T Luxton, Xue'Er Cheryl Lee, T Y Yuen, F J Ferrer, C W Johannes, D P Lane, C J Brown
Linear peptides can mimic and disrupt protein-protein interactions involved in critical cell signaling pathways. Such peptides however are usually protease sensitive and unable to engage with intracellular targets due to lack of membrane permeability. Peptide stapling has been proposed to circumvent these limitations but recent data has suggested that this method does not universally solve the problem of cell entry and can lead to molecules with off target cell lytic properties. To address these issues a library of stapled peptides was synthesized and screened to identify compounds that bound Mdm2 and activated cellular p53...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28491867/metabolic-reprogramming-in-glioma
#6
REVIEW
Marie Strickland, Elizabeth A Stoll
Many cancers have long been thought to primarily metabolize glucose for energy production-a phenomenon known as the Warburg Effect, after the classic studies of Otto Warburg in the early twentieth century. Yet cancer cells also utilize other substrates, such as amino acids and fatty acids, to produce raw materials for cellular maintenance and energetic currency to accomplish cellular tasks. The contribution of these substrates is increasingly appreciated in the context of glioma, the most common form of malignant brain tumor...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28483521/sterol-regulatory-element-binding-protein-1-inhibitors-decrease-pancreatic-cancer-cell-viability-and-proliferation
#7
Siqingaowa, Sathiya Sekar, Venkat Gopalakrishnan, Changiz Taghibiglou
Sterol regulatory element-binding protein1 (SREBP1) is a key regulatory factor that controls lipid homeostasis. Overactivation of SREBP1 and elevated lipid biogenesis are considered the major characteristics in malignancies of prostate cancer, endometrial cancer, and glioblastoma. However, the impact of SREBP1 activation in the progression of pancreatic cancer has not been explored. The present study examines the effect of suppression of SREBP1 activation by its inhibitors like fatostatin and PF429242 besides analyzing the impact of inhibitory effects on SREBP1 downstream signaling cascade such as fatty acid synthase (FAS), hydroxymethylglutaryl-CoA reductase (HMGCoAR), stearoyl-CoA desaturase-1 (SCD-1), and tumor suppressor protein p53 in MIA PaCa-2 pancreatic cancer cells...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28480888/hepatic-p63-regulates-steatosis-via-ikk%C3%AE-er-stress
#8
Begoña Porteiro, Marcos F Fondevila, Teresa C Delgado, Cristina Iglesias, Monica Imbernon, Paula Iruzubieta, Javier Crespo, Amaia Zabala-Letona, Johan Fernø, Bárbara González-Terán, Nuria Matesanz, Lourdes Hernández-Cosido, Miguel Marcos, Sulay Tovar, Anxo Vidal, Julia Sánchez-Ceinos, Maria M Malagon, Celia Pombo, Juan Zalvide, Arkaitz Carracedo, Xabier Buque, Carlos Dieguez, Guadalupe Sabio, Miguel López, Patricia Aspichueta, María L Martínez-Chantar, Ruben Nogueiras
p53 family members control several metabolic and cellular functions. The p53 ortholog p63 modulates cellular adaptations to stress and has a major role in cell maintenance and proliferation. Here we show that p63 regulates hepatic lipid metabolism. Mice with liver-specific p53 deletion develop steatosis and show increased levels of p63. Down-regulation of p63 attenuates liver steatosis in p53 knockout mice and in diet-induced obese mice, whereas the activation of p63 induces lipid accumulation. Hepatic overexpression of N-terminal transactivation domain TAp63 induces liver steatosis through IKKβ activation and the induction of ER stress, the inhibition of which rescues the liver functions...
May 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28459365/interaction-of-renin-angiotensin-system-and-adenosine-monophosphate-activated-protein-kinase-signaling-pathway-in-renal-carcinogenesis-of-uninephrectomized-rats
#9
Ke-Ke Yang, Yi Sui, Hui-Rong Zhou, Hai-Lu Zhao
Renin-angiotensin system and adenosine monophosphate-activated protein kinase signaling pathway both play important roles in carcinogenesis, but the interplay of renin-angiotensin system and adenosine monophosphate-activated protein kinase in carcinogenesis is not clear. In this study, we researched the interaction of renin-angiotensin system and adenosine monophosphate-activated protein kinase in renal carcinogenesis of uninephrectomized rats. A total of 96 rats were stratified into four groups: sham, uninephrectomized, and uninephrectomized treated with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28450114/the-novel-cyclophilin-d-inhibitor-compound-19-protects-retinal-pigment-epithelium-cells-and-retinal-ganglion-cells-from-uv-radiation
#10
Laiqing Xie, Long Cheng, Guoxu Xu, Ji Zhang, Xiaoyan Ji, E Song
Excessive Ultra violet (UV) radiation induces injuries to retinal pigment epithelium (RPE) cells (RPEs) and retinal ganglion cells (RGCs), causing retinal degeneration. Cyclophilin D (Cyp-D)-dependent mitochondrial permeability transition pore (mPTP) opening mediates UV-induced cell death. In this study, we show that a novel Cyp-D inhibitor compound 19 efficiently protected RPEs and RGCs from UV radiation. Compound 19-mediated cytoprotection requires Cyp-D, as it failed to further protect RPEs/RGCs from UV when Cyp-D was silenced by targeted shRNAs...
June 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28440512/astemizole-protects-against-human-umbilical-vein-endothelial-cell-injury-induced-by-hydrogen-peroxide-via-the-p53-signaling-pathway
#11
Jia-Nan Tian, Xiao-Dong Shi, Xiao-Kun Wang, Shuang Wang, Jing-Xue Xu, Chun-Xiao Yang
Astemizole has gained attention as an antineoplastic drug that targets important ion channels. The present study aimed to investigate the protective effects of astemizole against hydrogen peroxide (H2O2)‑induced oxidative damage to human umbilical vein endothelial cells (HUVECs). HUVECs were pretreated with astemizole (0.5 and 1 µM) for 12 h, then exposed to H2O2 (200 µM) for 12 h. Cell viability was measured using the MTT assay. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH‑Px), reactive oxygen species (ROS) and apoptotic percentage were determined...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28402948/c-type-natriuretic-peptide-modified-lipid-vesicles-fabrication-and-use-for-the-treatment-of-brain-glioma
#12
Jia-Shuan Wu, Li-Min Mu, Ying-Zi Bu, Lei Liu, Yan Yan, Ying-Jie Hu, Jing Bai, Jing-Ying Zhang, Weiyue Lu, Wan-Liang Lu
Chemotherapy of brain glioma faces a major obstacle owing to the inability of drug transport across the blood-brain barrier (BBB). Besides, neovasculatures in brain glioma site result in a rapid infiltration, making complete surgical removal virtually impossible. Herein, we reported a novel kind of C-type natriuretic peptide (CNP) modified vinorelbine lipid vesicles for transferring drug across the BBB, and for treating brain glioma along with disrupting neovasculatures. The studies were performed on brain glioma U87-MG cells in vitro and on glioma-bearing nude mice in vivo...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28381798/gallic-acid-and-dodecyl-gallate-prevents-carbon-tetrachloride-induced-acute-and-chronic-hepatotoxicity-by-enhancing-hepatic-antioxidant-status-and-increasing-p53-expression
#13
Marlene Raimunda Andreola Perazzoli, Camila Katerin Perondi, Cesar Milton Baratto, Evelyn Winter, Tânia Beatriz Creczynski-Pasa, Claudriana Locatelli
Gallic acid (3,4,5-trihydroxybenzoic acid, GA), a natural phenolic acid has been reported as a strong antioxidant. Therefore the present study was designed to evaluate the effects of GA and dodecyl gallate (DGA) against acute and chronic carbon tetrachloride (CCl4)-induced hepatotoxicity. For acute model, rats were orally treated with GA and DGA for 7 d prior to CCl4 by intraperitoneally (i.p.) injection. For the chronic model, rats were orally treated with GA or DGA and CCl4 i.p. twice a week for four weeks...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28359161/effective-medicinal-plant-in-cancer-treatment-part-2
#14
Wesam Kooti, Karo Servatyari, Masoud Behzadifar, Majid Asadi-Samani, Fatemeh Sadeghi, Bijan Nouri, Hadi Zare Marzouni
Cancer is the second cause of death after cardiovascular diseases. With due attention to rapid progress in the phytochemical study of plants, they are becoming popular because of their anticancer effects. The aim of this study was to investigate the effective medicinal plants in the treatment of cancer and study their mechanism of action. In order to gather information the keywords "traditional medicine," "plant compounds," "medicinal plant," "medicinal herb," "toxicity," "anticancer effect," "cell line," and "treatment" were searched in international databases such as ScienceDirect, PubMed, and Scopus and national databases such as Magiran, Sid, and Iranmedex, and a total of 228 articles were collected...
January 1, 2017: Journal of Evidence-based Complementary & Alternative Medicine
https://www.readbyqxmd.com/read/28357524/molecular-connections-of-obesity-and-aging-a-focus-on-adipose-protein-53-and-retinoblastoma-protein
#15
REVIEW
Dinh-Toi Chu, Yang Tao
Obesity is an induced health problem that human beings have been facing with non-optimal treatment so far. Humans are on average getting fatter with age, and obesity and aging interact each other to shorten lifetime and decrease life quality. Obesity also causes several aging related-disorders such as cancer, strokes, cardiovascular disease, high blood pressure and type 2 diabetes. So, the molecular connections between aging and obesity are promising targets for bio-medical researches and innovative therapies of many health problems...
June 2017: Biogerontology
https://www.readbyqxmd.com/read/28348409/inhibiting-the-system-xc-glutathione-axis-selectively-targets-cancers-with-mutant-p53-accumulation
#16
David S Liu, Cuong P Duong, Sue Haupt, Karen G Montgomery, Colin M House, Walid J Azar, Helen B Pearson, Oliver M Fisher, Matthew Read, Glen R Guerra, Ygal Haupt, Carleen Cullinane, Klas G Wiman, Lars Abrahmsen, Wayne A Phillips, Nicholas J Clemons
TP53, a critical tumour suppressor gene, is mutated in over half of all cancers resulting in mutant-p53 protein accumulation and poor patient survival. Therapeutic strategies to target mutant-p53 cancers are urgently needed. We show that accumulated mutant-p53 protein suppresses the expression of SLC7A11, a component of the cystine/glutamate antiporter, system xC(-), through binding to the master antioxidant transcription factor NRF2. This diminishes glutathione synthesis, rendering mutant-p53 tumours susceptible to oxidative damage...
March 28, 2017: Nature Communications
https://www.readbyqxmd.com/read/28347692/mir-21-5p-203a-3p-promote-ox-ldl-induced-endothelial-cell-senescence-through-down-regulation-of-mitochondrial-fission-protein-drp1
#17
Jie-Jie Zhang, Wei-Qi Liu, Jing-Jie Peng, Qi-Lin Ma, Jun Peng, Xiu-Ju Luo
This study aims to identify both endothelia-specific/enriched and senescence-associated miRNAs as well as their functions. The rats were fed on high-fat diet to establish a hyperlipidemic model, which showed an increase in plasma lipids and acceleration in endothelial senescence and endothelial dysfunction, accompanied by alterations in 7 endothelia-specific/enriched and senescence-associated miRNAs. Among the 7 selected miRNAs, miR-21-5p and miR-203a-3p were significantly up-regulated in a human umbilical vein endothelial cells (HUVECs) senescent model induced by ox-LDL, consistent with their changes in the hyperlipidemic rats...
March 24, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28335726/analysis-of-hepatic-transcript-profile-and-plasma-lipid-profile-in-early-lactating-dairy-cows-fed-grape-seed-and-grape-marc-meal-extract
#18
Denise K Gessner, Anne Winkler, Christian Koch, Georg Dusel, Gerhard Liebisch, Robert Ringseis, Klaus Eder
BACKGROUND: It was recently reported that dairy cows fed a polyphenol-rich grape seed and grape marc meal extract (GSGME) during the transition period had an increased milk yield, but the underlying reasons remained unclear. As polyphenols exert a broad spectrum of metabolic effects, we hypothesized that feeding of GSGME influences metabolic pathways in the liver which could account for the positive effects of GSGME in dairy cows. In order to identify these pathways, we performed genome-wide transcript profiling in the liver and lipid profiling in plasma of dairy cows fed GSGME during the transition period at 1 week postpartum...
March 23, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28334197/ppar%C3%AE-regulates-tumor-cell-proliferation-and-senescence-via-a-novel-target-gene-carnitine-palmitoyltransferase-1c
#19
Yixin Chen, Yongtao Wang, Yaoyao Huang, Hang Zeng, Bingfang Hu, Lihuan Guan, Huizhen Zhang, Ai-Ming Yu, Caroline H Johnson, Frank J Gonzalez, Min Huang, Huichang Bi
Carnitine palmitoyltransferase 1C (CPT1C), an enzyme located in the outer mitochondria membrane, has a crucial role in fatty acid transport and oxidation. It is also involved in cell proliferation and is a potential driver for cancer cell senescence. However, its upstream regulatory mechanism is unknown. Peroxisome proliferator activated receptor α (PPARα) is a ligand-activated transcription factor that regulates lipid metabolism and tumor progression. The current study aimed to elucidate whether and how PPARα regulates CPT1C and then affects cancer cell proliferation and senescence...
April 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28315003/anti-oxidative-responses-on-hepatic-tissue-of-zebrafish-danio-rerio-in-a-short-duration-of-sub-lethal-concentrations-of-cadmium-exposure
#20
Su Mei Wu, Li-Hsin Shu, Jia-Hao Liu, Ching Hsein Chen
The aim of the present study was to identify whether the responses of oxidative stress in zebrafish liver are similar to those in mammalians upon low doses of Cd(2+) exposure in short durations. Fish were exposed to 1.78 μM Cd(2+) (treatment) and 0.0 μM Cd(2+) (control) for 0, 1, 3, and 6 h. The reactive oxygen species (ROS) and lipid peroxidation (LPO) of hepatic tissues significantly increased after 3 and 6 h of Cd(2+) exposure, respectively. Antioxidants glutathione peroxidase (gpx1a), superoxide dismutase (sod), and catalase (cat) were up regulated after 1-3 h, and metallothionein isoforms (smtB and mt2) increased after 3-6 h of Cd(2+) exposure...
May 2017: Bulletin of Environmental Contamination and Toxicology
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