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https://www.readbyqxmd.com/read/27922102/slc2a8-glut8-is-a-mammalian-trehalose-transporter-required-for-trehalose-induced-autophagy
#1
Allyson L Mayer, Cassandra B Higgins, Monique R Heitmeier, Thomas E Kraft, Xia Qian, Jan R Crowley, Krzysztof L Hyrc, Wandy L Beatty, Kevin E Yarasheski, Paul W Hruz, Brian J DeBosch
Trehalose is a disaccharide demonstrated to mitigate disease burden in multiple murine neurodegenerative models. We recently revealed that trehalose rapidly induces hepatic autophagy and abrogates hepatic steatosis by inhibiting hexose transport via the SLC2A family of facilitative transporters. Prior studies, however, postulate that intracellular trehalose is sufficient to induce cellular autophagy. The objective of the current study was to identify the means by which trehalose accesses the hepatocyte cytoplasm, and define the distal signaling mechanisms by which trehalose induces autophagy...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27920093/metformin-reduces-glycometabolism-of-papillary-thyroid-carcinoma-in-vitro-and-in-vivo
#2
Chen-Tian Shen, Wei-Jun Wei, Zhong-Ling Qiu, Hong-Jun Song, Xin-Yun Zhang, Zhen-Kui Sun, Quan-Yong Luo
More aggressive thyroid cancer cells show a higher activity of glycometabolism. Targeting cancer cell metabolism has emerged as a novel approach to prevent or treat malignant tumors. Glucose metabolism regulation effect of metformin in papillary thyroid cancer was investigated in the current study. Human papillary thyroid carcinoma (PTC) cell lines BCPAP and KTC1 were used. Cell viability was detected by CCK8 assay. Glucose uptake and relative gene expression were measured in metformin (0-10 mM for 48 h)-treated cells by (18)F-FDG uptake assay and western blotting analysis, respectively...
January 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/27919304/green-tea-extract-intake-during-lactation-modified-cardiac-macrophage-infiltration-and-amp-activated-protein-kinase-phosphorylation-in-weanling-rats-from-undernourished-mother-during-gestation-and-lactation
#3
E Matsumoto, S Kataoka, Y Mukai, M Sato, S Sato
Maternal dietary restriction is often associated with cardiovascular disease in offspring. The aim of this study was to investigate the effect of green tea extract (GTE) intake during lactation on macrophage infiltration, and activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and serine-threonine kinase Akt (Akt) in the hearts of weanlings exposed to maternal dietary protein restriction. Pregnant Wistar rats were fed control (C) or low-protein diets (LP) throughout gestation. Following delivery, the dams received a control or a GTE-containing control diet during lactation: control diet during gestation and lactation (CC), low-protein diet during gestation and lactation (LPC), low-protein diet during gestation and 0...
December 6, 2016: Journal of Developmental Origins of Health and Disease
https://www.readbyqxmd.com/read/27919208/is-metformin-a-therapeutic-paradigm-for-colorectal-cancer-insight-into-the-molecular-pathway
#4
Zar Chii Thent, Nurul Hannim Zaidun, Fairuz Azmi, Mu Izuddin Senin, Haszianaliza Haslan, Ahmad Ruzain Salehuddin
Colorectal cancer (CRC) remains one of the major leading causes of cancer related morbidity and mortality. Apart from the conventional anti-neoplastic agents, metformin, a biguanide anti-diabetic agent, has recently found to have anti-cancer property. Several studies observed the effect of metformin towards its anti-cancer effect on colon or colorectal cancer in diabetic patients. However, only a few studies showed its effect on colorectal cancer in relation to the non-diabetic status. The present review aimed to highlight the insight into the molecular pathway of metformin towards colorectal cancer in the absence of diabetes mellitus...
December 5, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/27919065/splicing-factor-1-modulates-dietary-restriction-and-torc1-pathway-longevity-in-c-elegans
#5
Caroline Heintz, Thomas K Doktor, Anne Lanjuin, Caroline C Escoubas, Yue Zhang, Heather J Weir, Sneha Dutta, Carlos Giovanni Silva-García, Gitte H Bruun, Ianessa Morantte, Gerta Hoxhaj, Brendan D Manning, Brage S Andresen, William B Mair
Ageing is driven by a loss of transcriptional and protein homeostasis and is the key risk factor for multiple chronic diseases. Interventions that attenuate or reverse systemic dysfunction associated with age therefore have the potential to reduce overall disease risk in the elderly. Precursor mRNA (pre-mRNA) splicing is a fundamental link between gene expression and the proteome, and deregulation of the splicing machinery is linked to several age-related chronic illnesses. However, the role of splicing homeostasis in healthy ageing remains unclear...
December 5, 2016: Nature
https://www.readbyqxmd.com/read/27919027/phosphorylation-of-janus-kinase-1-jak1-by-amp-activated-protein-kinase-ampk-links-energy-sensing-to-anti-inflammatory-signaling
#6
Claire Rutherford, Claire Speirs, Jamie J L Williams, Marie-Ann Ewart, Sarah J Mancini, Simon A Hawley, Christian Delles, Benoit Viollet, Ana P Costa-Pereira, George S Baillie, Ian P Salt, Timothy M Palmer
Adenosine 5'-monophosphate-activated protein kinase (AMPK) is a pivotal regulator of metabolism at cellular and organismal levels. AMPK also suppresses inflammation. We found that pharmacological activation of AMPK rapidly inhibited the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway in various cells. In vitro kinase assays revealed that AMPK directly phosphorylated two residues (Ser(515) and Ser(518)) within the Src homology 2 domain of JAK1. Activation of AMPK enhanced the interaction between JAK1 and 14-3-3 proteins in cultured vascular endothelial cells and fibroblasts, an effect that required the presence of Ser(515) and Ser(518) and was abolished in cells lacking AMPK catalytic subunits...
November 8, 2016: Science Signaling
https://www.readbyqxmd.com/read/27919004/irbesartan-ameliorates-hyperlipidemia-and-liver-steatosis-in-type-2-diabetic-db-db-mice-via-stimulating-ppar-%C3%AE-ampk-akt-mtor-signaling-and-autophagy
#7
Juan Zhong, Wangqiu Gong, Lu Lu, Jing Chen, Zibin Lu, HongYu Li, Wenting Liu, Yangyang Liu, Mingqing Wang, Rong Hu, Haibo Long, Lianbo Wei
Irbesartan (Irb), a unique subset of angiotensin II receptor blockers (ARBs) with PPAR-γ activation function, has been reported to play a role in renal dysfunction, glucose metabolism, and abnormal lipid profile in diabetic animal models and humans. However, the underlying mechanisms that improve hyperlipidemia and liver steatosis are unclear. This study investigated the effects of Irb on lipid metabolism and hepatic steatosis using the spontaneous type 2 diabetic db/db mouse model. The results demonstrated body and liver weight, food consumption, lipid content in serum and liver tissue, and liver dysfunction as well as hepatic steatosis were increased in db/db mice compared with db/m mice, whereas the increases were reversed by Irb treatment...
December 2, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27917887/13-methylberberine-a-berberine-analogue-with-stronger-anti-adipogenic-effects-on-mouse-3t3-l1-cells
#8
Yit-Lai Chow, Mami Sogame, Fumihiko Sato
Lipid metabolism modulation is a main focus of metabolic syndrome research, an area in which many natural and synthetic chemicals are constantly being screened for in vitro and in vivo activity. Berberine, a benzylisoquinoline plant alkaloid, has been extensively investigated for its anti-obesity effects and as a potential cholesterol and triglyceride-lowering drug. We screened 11 protoberberine and 2 benzophenanthridine alkaloids for their anti-adipogenic effects on 3T3-L1 adipocytes and found that 13-methylberberine exhibited the most potent activity...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27917698/tetramethylpyrazine-protects-against-glucocorticoid-induced-apoptosis-by-promoting-autophagy-in-mesenchymal-stem-cells-and-improves-bone-mass-in-glucocorticoid-induced-osteoporosis-rats
#9
Long Wang, Hong-Yang Zhang, Bo Gao, Jun Shi, Qiang Huang, Yue-Hu Han, Ya-Qian Hu, Wei-Guang Lu, Zhuo-Jie Zhao, Bao-Hua Liu, Qiang Jie, Liu Yang, Zhuo-Jing Luo
Glucocorticoid-induced osteoporosis (GIOP) is a widespread clinical complication due to the common use of glucocorticoids. Excess glucocorticoids induce apoptosis of bone marrow-derived mesenchymal stem cells (BMSCs), which have been shown to play an increasingly important role in the pathogenesis and therapy of osteoporosis. Tetramethylpyrazine (TMP), an extract from one of the most recognized herbs in traditional Chinese medicine (Chuanxiong), has been reported to have anti-apoptotic properties. In this study, we tested whether TMP protects rat BMSCs following exposure to glucocorticoids in vitro and in vivo...
December 4, 2016: Stem Cells and Development
https://www.readbyqxmd.com/read/27917437/nicotine-plus-a-high-fat-diet-triggers-cardiomyocyte-apoptosis
#10
Indrani Sinha-Hikim, Theodore C Friedman, Mark Falz, Victor Chalfant, Mohammad Kamrul Hasan, Jorge Espinoza-Derout, Desean L Lee, Carl Sims, Peter Tran, Sushil K Mahata, Amiya P Sinha-Hikim
Cigarette smoking is an important risk factor for diabetes, cardiovascular disease and non-alcoholic fatty liver disease. The health risk associated with smoking can be aggravated by obesity. Smoking might also trigger cardiomyocyte (CM) apoptosis. Given that CM apoptosis has been implicated as a potential mechanism in the development of cardiomyopathy and heart failure, we characterize the key signaling pathways in nicotine plus high-fat diet (HFD)-induced CM apoptosis. Adult C57BL6 male mice were fed a normal diet (ND) or HFD and received twice-daily intraperitoneal (IP) injections of nicotine (0...
December 5, 2016: Cell and Tissue Research
https://www.readbyqxmd.com/read/27916732/ghrelin-improves-vascular-autophagy-in-rats-with-vascular-calcification
#11
Mingming Xu, Lin Liu, Chenfang Song, Wei Chen, Shuyan Gui
BACKGROUNDS: This study aimed to investigate whether ghrelin ameliorated vascular calcification (VC) through improving autophagy. METHODS: VC model was induced by nicotine plus vitamin D3 in rats and β-glycerophosphate in vascular smooth muscle cell (VSMC). Calcium deposition was detected by von Kossa staining or alizarin red S staining. ALP activity was also detected. Western blot was used to assess the protein expression. RESULTS: Ghrelin treatment attenuated the elevation of calcium deposition and ALP activity in VC model both in vivo and in vitro...
December 1, 2016: Life Sciences
https://www.readbyqxmd.com/read/27916511/liqustri-lucidi-fructus-inhibits-hepatic-injury-and-functions-as-an-antioxidant-by-activation-of-amp-activated-protein-kinase-in-vivo-and-in-vitro
#12
Hye Lim Seo, Su Youn Baek, Eun Hye Lee, Ju-Hee Lee, Seul-Gi Lee, Kwang-Youn Kim, Mi Hee Jang, Min-Hui Park, Joung-Hee Kim, Keun-Jun Kim, Hyeong Sik Lee, Soon-Cheol Ahn, Jong Rok Lee, Sook Jahr Park, Sang Chan Kim, Young Woo Kim
Medicinal herbs are used to treat or prevent various diseases, and function to regulate protective mechanisms as nutraceuticals. Fructus Ligustri lucidi is the fruit of Ligustrum lucidum and has been used for its tonic effects on the liver. This study was designed to examine the effects of Fructus Ligustri lucidi water extract (FLL) against severe oxidative stress and mitochondrial impairment in vivo and in vitro and to elucidate its cellular mechanisms of action. Treatment of HepG2 cells with arachidonic acid (AA) + iron successfully induced oxidative stress and apoptosis, as indicated by depletion of glutathione, formation of ROS, increases in mitochondrial membrane permeability (MMP), and altered expression of apoptosis-related proteins, such as procaspase-3 and Bcl-xL...
December 1, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27916296/ampk%C3%AE-is-suppressed-in-bladder-cancer-through-macrophage-mediated-mechanisms
#13
Stavros Kopsiaftis, Poornima Hegde, John A Taylor, Kevin P Claffey
Bladder cancer presents as either low- or high-grade disease, each with distinct mutational profiles; however, both display prominent mTORC1 activation. One major negative regulator of mTORC1 is AMPK, which is a critical metabolic regulator that suppresses cellular growth in response to metabolic stress by negatively regulating mTORC1. Alterations in the activation and protein levels of AMPK have been reported in breast, gastric, and hepatocellular carcinoma. To investigate whether AMPK suppression is responsible for mTOR activation in bladder cancer, the levels of AMPKα were quantified in a cohort of primary human bladder cancers and adjacent nontumor tissues...
December 2016: Translational Oncology
https://www.readbyqxmd.com/read/27914812/protective-effects-of-gomisin-n-against-hepatic-steatosis-through-ampk-activation
#14
Ye-Rang Yun, Ji-Hyun Kim, Ji Ha Kim, Myeong Ho Jung
Gomisin N (GN) is a phytochemical derived from Schisandra chinensis. It has been reported to exert a protective effect against hepatic steatosis by attenuating endoplasmic recticulum (ER) stress. However, the detailed mechanism by which GN inhibits hepatic steatosis remains to be elucidated. In this study, we examined whether GN activates AMP-activated protein kinase (AMPK) and exerts therapeutic effects on liver X receptor (LXR)- or palmitic acid (PA)-induced triglyceride (TG) accumulation in HepG2 cells. Furthermore, in vivo protective effects of GN against hepatic steatosis were assessed in high-fat diet (HFD)-induced obese mice...
November 30, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27913948/branched-chain-amino-acids-administration-suppresses-endurance-exercise-related-activation-of-ubiquitin-proteasome-signaling-in-trained-human-skeletal-muscle
#15
Evgeny A Lysenko, Tatiana F Vepkhvadze, Egor M Lednev, Olga L Vinogradova, Daniil V Popov
We tested whether post exercise ingestion of branched-chain amino acids (BCAA < 10 g) is sufficient to activate signaling associated with muscle protein synthesis and suppress exercise-induced activation of mechanisms associated with proteolysis in endurance-trained human skeletal muscle. Nine endurance-trained athletes performed a cycling bout with and without BCAA ingestion (0.1 g/kg). Post exercise ACC(Ser79/222) phosphorylation (endogenous marker of AMPK activity) was increased (~3-fold, P < 0...
December 3, 2016: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/27913573/thyroid-hormones-induce-browning-of-white-fat
#16
Noelia Martinez, José María Moreno-Navarrete, Cristina Contreras, Eva Rial-Pensado, Johan Fernø, Rubén Nogueiras, Carlos Diéguez, José M Fernández-Real, Miguel López
The canonical view about the effect of thyroid hormones (THs) on thermogenesis assumes that the hypothalamus acts merely as a modulator of the sympathetic outflow on brown adipose tissue (BAT). Recent data have challenged that vision by demonstrating that THs act on the ventromedial nucleus of the hypothalamus (VMH) to inhibit AMP-activated protein kinase (AMPK), which regulates the thermogenic program in BAT, leading to increased thermogenesis and weight loss. Current data have shown that in addition to activation of brown fat, the browning of white adipose tissue (WAT) might be also an important thermogenic mechanism...
December 2, 2016: Journal of Endocrinology
https://www.readbyqxmd.com/read/27913299/the-inhibitory-effect-of-beta-lapachone-on-rankl-induced-osteoclastogenesis
#17
Dong Ryun Gu, Joon No Lee, Gi-Su Oh, Hyung Jin Kim, Min Seuk Kim, Seoung Hoon Lee
β-lapachone (β-L) is a substrate of reduced nicotinamide adenine dinucleotide (NADH): quinone oxidoreductase 1 (NQO1). NQO1 reduces quinones to hydroquinones using NADH as an electron donor and consequently increases the intracellular NAD+/NADH ratio. The activation of NQO1 by β-L has beneficial effects on several metabolic syndromes, such as obesity, hypertension, and renal injury. However, the effect of β-L on bone metabolism remains unclear. Here, we show that β-L might be a potent inhibitor of receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis...
November 30, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27912736/citrus-junos-tanaka-peel-ameliorates-hepatic-lipid-accumulation-in-hepg2-cells-and-in-mice-fed-a-high-cholesterol-diet
#18
Eun Ju Shin, Jae Ho Park, Mi Jeong Sung, Min-Yu Chung, Jin-Taek Hwang
BACKGROUND: Citrus junos Tanaka (yuja), a yellow-coloured citrus fruit has traditionally been consumed in Korea, Japan, and China and has been found effective in preventing certain diseases. However, the inhibitory effect of yuja on hepatic lipid accumulation has not been clearly elucidated thus far. METHODS: The inhibitory effect of yuja on hepatic lipid accumulation was investigated in both cell culture and mouse models. We investigated the inhibitory effect of ethanol extract of yuja peel (YE) using HepG2 cells...
December 3, 2016: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/27912206/irisin-lowers-blood-pressure-by-improvement-of-endothelial-dysfunction-via-ampk-akt-enos-no-pathway-in-the-spontaneously-hypertensive-rat
#19
Jinjuan Fu, Yu Han, Jialiang Wang, Yukai Liu, Shuo Zheng, Lin Zhou, Pedro A Jose, Chunyu Zeng
BACKGROUND: Exercise is a major nonpharmacological treatment for hypertension, but its underlying mechanisms are still not completely elucidated. Irisin, a polypeptide containing 112 amino acids, which is secreted mainly by skeletal muscle cells during exercise, exerts a protective role in metabolic diseases, such as diabetes mellitus and obesity. Because of the close relationship between irisin and metabolic diseases, we hypothesized that irisin may play a role in the regulation of blood pressure...
October 26, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27911275/microrna-25-targets-pkc%C3%AE-and-protects-osteoblastic-cells-from-dexamethasone-via-activating-ampk-signaling
#20
Jian-Bo Fan, Wei Liu, Xin-Hui Zhu, Hong Yi, Sheng-Yu Cui, Jian-Ning Zhao, Zhi-Ming Cui
AMP-activated protein kinase (AMPK) activation could protect osteoblasts from dexamethasone (Dex). This study aims to provoke AMPK activation via microRNA downregulation of its negative regulator protein kinase C ζ (PKCζ). Results show that microRNA-25-5p (miR-25-5p) targets PKCζ's 3' untranslated regions (UTRs). Forced-expression of miR-25 downregulated PKCζ and activated AMPK in human osteoblastic cells (OB-6 and hFOB1.19 lines), which thereafter protected cells from Dex. Reversely, expression of antagomiR-25, the miR-25 inhibitor, upregulated PKCζ and inhibited AMPK activation, exacerbating Dex damages...
November 29, 2016: Oncotarget
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