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https://www.readbyqxmd.com/read/28489607/trans-scirpusin-a-showed-antitumor-effects-via-autophagy-activation-and-apoptosis-induction-of-colorectal-cancer-cells
#1
Eun-Hye Hong, Eun-Young Heo, Jae-Hyoung Song, Bo-Eun Kwon, Jae-Young Lee, Yaejeong Park, Jinwoong Kim, Sun-Young Chang, Young-Won Chin, Sang-Min Jeon, Hyun-Jeong Ko
Trans-Scirpusin A (TSA) is a resveratrol oligomer found in Borassus flabellifer L. We found that TSA inhibited the growth of colorectal cancer Her2/CT26 cells in vivo in mice. Although some cytotoxic T lymphocytes (CTLs) were induced against the tumor-associated antigen Her2, TSA treatment did not significantly increase the level of Her2-specific CTL response compared to that with vehicle treatment. However, there was a significant increase in the level of TNF-α mRNA in tumor tissue and Her2-specific Ab (antibody) production...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28480026/exercise-training-provides-cardioprotection-by-activating-and-coupling-endothelial-nitric-oxide-synthase-via-a-%C3%AE-3-adrenergic-receptor-amp-activated-protein-kinase-signaling-pathway
#2
Larry A Barr, Jonathan P Lambert, Yuuki Shimizu, Lili A Barouch, Nawazish Naqvi, John W Calvert
Exercise training confers sustainable protection against ischemia/reperfusion injury. However, the mechanism by which this process occurs is not fully understood. Previously, it was shown that β3-adrenergic receptors (β3-ARs) play a critical role in regulating the activation of endothelial nitric oxide synthase (eNOS) in response to exercise and play a critical role in exercise-mediated cardioprotection. Intriguingly, a deficiency in β3-ARs led to increased myocardial injury following exercise training. The purpose of the current study was to determine mechanisms by which β3-ARs are linked to eNOS activation and to determine the mechanism responsible for the exacerbated ischemia/reperfusion injury displayed by β3-AR deficient (β3-AR KO) mice after exercise training...
January 2017: Medical Gas Research
https://www.readbyqxmd.com/read/28477305/long-term-obestatin-treatment-of-mice-type-2-diabetes-increases-insulin-sensitivity-and-improves-liver-function
#3
Paweł A Kołodziejski, Ewa Pruszyńska-Oszmałek, Mathias Z Strowski, Krzysztof W Nowak
PURPOSE: Obestatin and ghrelin are peptides encoded by the preproghrelin gene. Obestatin inhibits food intake, in addition to regulation of glucose and lipid metabolism. Here, we test the ability of obestatin at improving metabolic control and liver function in type 2 diabetic animals (type 2 diabetes mellitus). METHODS: The effects of chronic obestatin treatment of mice with experimentally induced type 2 diabetes mellitus on serum levels of glucose and lipids, and insulin sensitivity are characterized...
June 2017: Endocrine
https://www.readbyqxmd.com/read/28474247/inhibition-of-angiotensin-ii-induced-cardiac-fibrosis-by-atorvastatin-in-adiponectin-knockout-mice
#4
Sun Young Choi, Jong Sung Park, Mee Sook Roh, Chong-Rak Kim, Moo Hyun Kim, Victor Serebruany
Adiponectin is a polypeptide known to inhibit cardiac fibrosis via the activation of ‎adenosine monophosphate-activated protein kinase (AMPK). Statins can also activate AMPK, resulting in the secretion of adiponectin. We determined whether atorvastatin inhibits angiotensin II-induced cardiac fibrosis (AICF) in the presence or absence of adiponectin. Adiponectin knockout (APN-KO, n = 44) and wild type (WT, n = 44) mice were received subcutaneous angiotensin II (1.5 mg/kg/day), and atorvastatin (10 mg/kg/day) was administered orally for 15 days...
May 4, 2017: Lipids
https://www.readbyqxmd.com/read/28472467/hypothalamic-regulation-of-liver-and-muscle-nutrient-partitioning-by-brain-specific-carnitine-palmitoyltransferase-1c-cpt1c-in-male-mice
#5
Macarena Pozo, Rosalía Rodríguez-Rodríguez, Sara Ramírez, Patricia Seoane-Collazo, Miguel López, Dolors Serra, Laura Herrero, Núria Casals
Carnitine palmitoyltransferase 1C (CPT1C), a brain-specific protein localized in the endoplasmic reticulum of neurons, is expressed in almost all brain regions. Based on global knockout (KO) models, CPT1C has demonstrated relevance in hippocampus-dependent spatial learning as well as in hypothalamic regulation of energy balance. Specifically, it has been shown that CPT1C is protective against high-fat diet-induced obesity (DIO), and that CPT1C KO mice show reduced peripheral fatty acid oxidation (FAO) both during fasting and DIO...
May 3, 2017: Endocrinology
https://www.readbyqxmd.com/read/28389470/rac1-and-ampk-account-for-the-majority-of-muscle-glucose-uptake-stimulated-by-ex-vivo-contraction-but-not-in-vivo-exercise
#6
Lykke Sylow, Lisbeth L V Møller, Maximilian Kleinert, Gommaar D'Hulst, Estelle De Groote, Peter Schjerling, Gregory R Steinberg, Thomas E Jensen, Erik A Richter
Exercise bypasses insulin resistance to increase glucose uptake in skeletal muscle and therefore represents an important alternative to stimulate glucose uptake in insulin resistant muscle. Both Rac1 and AMPK have been shown to partly regulate contraction-stimulated muscle glucose uptake but whether those two signaling pathways jointly account for the entire signal to glucose transport is unknown. We therefore studied the ability of contraction and exercise to stimulate glucose transport in isolated muscles with AMPK loss-of-function combined with either pharmacological inhibition or genetic deletion of Rac1...
April 7, 2017: Diabetes
https://www.readbyqxmd.com/read/28179232/kidney-specific-genetic-deletion-of-both-ampk-%C3%AE-subunits-causes-salt-and-water-wasting
#7
Yoskaly Lazo-Fernández, Goretti Baile, Patricia Meade, Pilar Torcal, Laura Martínez, Carmen Ibañez, Maria Luisa Bernal, Benoit Viollet, Ignacio Giménez
AMP-activated kinase (AMPK) controls cell energy homeostasis by modulating ATP synthesis and expenditure. In vitro studies have suggested AMPK may also control key elements of renal epithelial electrolyte transport but in vivo physiological confirmation is still insufficient. We studied sodium renal handling and extracellular volume regulation in mice with genetic deletion of AMPK catalytic subunits. AMPKα1 knockout (KO) mice exhibit normal renal sodium handling and a moderate antidiuretic state. This is accompanied by higher urinary aldosterone excretion rates and reduced blood pressure...
February 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28135761/palmitoleic-acid-reduces-the-inflammation-in-lps-stimulated-macrophages-by-inhibition-of-nf%C3%AE%C2%BAb-independently-of-ppars
#8
Camila O Souza, Alexandre A S Teixeira, Luana A Biondo, Loreana S Silveira, Philip Calder, José C Rosa Neto
Palmitoleic acid (PM, 16:1n-7) has anti-inflammatory properties that could be linked to higher expression of PPARα, an inhibitor of NFκB. Macrophages play a major role in the pathogenesis of chronic inflammation, however, the effects of PM on macrophages are underexplored. Thus, we aimed to investigate the effects of PM in activated macrophages as well the role of PPARα. Primary macrophages were isolated from C57BL6 (WT) and PPARα knockout (KO) mice, cultured under standard conditions and exposed to LPS (2...
January 30, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28123939/global-ip6k1-deletion-enhances-temperature-modulated-energy-expenditure-which-reduces-carbohydrate-and-fat-induced-weight-gain
#9
Qingzhang Zhu, Sarbani Ghoshal, Richa Tyagi, Anutosh Chakraborty
OBJECTIVE: IP6 kinases (IP6Ks) regulate cell metabolism and survival. Mice with global (IP6K1-KO) or adipocyte-specific (AdKO) deletion of IP6K1 are protected from diet induced obesity (DIO) at ambient (23 °C) temperature. AdKO mice are lean primarily due to increased AMPK mediated thermogenic energy expenditure (EE). Thus, at thermoneutral (30 °C) temperature, high fat diet (HFD)-fed AdKO mice expend energy and gain body weight, similar to control mice. IP6K1 is ubiquitously expressed; thus, it is critical to determine to what extent the lean phenotype of global IP6K1-KO mice depends on environmental temperature...
January 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28107516/liver-amp-activated-protein-kinase-is-unnecessary-for-gluconeogenesis-but-protects-energy-state-during-nutrient-deprivation
#10
Clinton M Hasenour, D Emerson Ridley, Freyja D James, Curtis C Hughey, E Patrick Donahue, Benoit Viollet, Marc Foretz, Jamey D Young, David H Wasserman
AMPK is an energy sensor that protects cellular energy state by attenuating anabolic and promoting catabolic processes. AMPK signaling is purported to regulate hepatic gluconeogenesis and substrate oxidation; coordination of these processes is vital during nutrient deprivation or pathogenic during overnutrition. Here we directly test hepatic AMPK function in regulating metabolic fluxes that converge to produce glucose and energy in vivo. Flux analysis was applied in mice with a liver-specific deletion of AMPK (L-KO) or floxed control littermates to assess rates of hepatic glucose producing and citric acid cycle (CAC) fluxes...
2017: PloS One
https://www.readbyqxmd.com/read/28096359/%C3%AE-synuclein-binds-and-sequesters-pike-l-into-lewy-bodies-triggering-dopaminergic-cell-death-via-ampk-hyperactivation
#11
Seong Su Kang, Zhentao Zhang, Xia Liu, Fredric P Manfredsson, Li He, P Michael Iuvone, Xuebing Cao, Yi E Sun, Lingjing Jin, Keqiang Ye
The abnormal aggregation of fibrillar α-synuclein in Lewy bodies plays a critical role in the pathogenesis of Parkinson's disease. However, the molecular mechanisms regulating α-synuclein pathological effects are incompletely understood. Here we show that α-synuclein binds phosphoinositide-3 kinase enhancer L (PIKE-L) in a phosphorylation-dependent manner and sequesters it in Lewy bodies, leading to dopaminergic cell death via AMP-activated protein kinase (AMPK) hyperactivation. α-Synuclein interacts with PIKE-L, an AMPK inhibitory binding partner, and this action is increased by S129 phosphorylation through AMPK and is decreased by Y125 phosphorylation via Src family kinase Fyn...
January 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27941154/controlling-skeletal-muscle-cpt-i-malonyl-coa-sensitivity-the-importance-of-ampk-independent-regulation-of-intermediate-filaments-during-exercise
#12
Paula M Miotto, Gregory R Steinberg, Graham P Holloway
The obligatory role of carnitine palmitoyltransferase-I (CPT-I) in mediating mitochondrial lipid transport is well established, a process attenuated by malonyl-CoA (M-CoA). However, the necessity of reducing M-CoA concentrations to promote lipid oxidation has recently been challenged, suggesting external regulation on CPT-I. Since previous work in hepatocytes suggests the involvement of the intermediate filament fraction of the cytoskeleton in regulating CPT-I, we investigated in skeletal muscle if CPT-I sensitivity for M-CoA inhibition could be regulated by the intermediate filaments, and whether AMP-activated protein kinase (AMPK) could be involved in this process...
February 15, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/27939519/13-ethylberberine-reduces-hmgb1-release-through-ampk-activation-in-lps-activated-raw264-7-cells-and-protects-endotoxemic-mice-from-organ-damage
#13
Dong Ung Lee, Young Shin Ko, Hye Jung Kim, Ki Churl Chang
High mobility group box 1 (HMGB1), a highly conserved non-histone DNA-binding protein, plays an important role in the pathogenesis of sepsis. Previously, the authors reported 13-ethylberberine (13-EBR) has anti-inflammatory and antibacterial effects. However, the effect of 13-EBR on HMGB1 release was not investigated. In the present study, it was hypothesized 13-EBR might reduce HMGB1 release by activating AMPK under septic conditions. The results obtained showed 13-EBR significantly reduced HMGB1 release from LPS-activated RAW264...
February 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27925195/palmitoleic-acid-improves-metabolic-functions-in-fatty-liver-by-ppar%C3%AE-dependent-ampk-activation
#14
Camila O de Souza, Alexandre A S Teixeira, Luana A Biondo, Edson A Lima Junior, Helena A P Batatinha, Jose C Rosa Neto
BACKGROUND: Palmitoleic acid, since described as lipokine, increases glucose uptake by modulation of 5'AMP-activated protein kinase (AMPK), as well as increasing lipolysis by activation of peroxisome proliferator-activated receptor-α (PPARα), in adipose tissue. However, in liver, the effects of palmitoleic acid on glucose metabolism and the role of PPARα remain unknown. OBJECTIVE: To investigate whether palmitoleic acid improved the hepatic insulin sensitivity of obese mice...
August 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27895577/fus1-ko-mouse-as-a-model-of-oxidative-stress-mediated-sporadic-alzheimer-s-disease-circadian-disruption-and-long-term-spatial-and-olfactory-memory-impairments
#15
Guillermo Coronas-Samano, Keeley L Baker, Winston J T Tan, Alla V Ivanova, Justus V Verhagen
Insufficient advances in the development of effective therapeutic treatments of sporadic Alzheimer's Disease (sAD) to date are largely due to the lack of sAD-relevant animal models. While the vast majority of models do recapitulate AD's hallmarks of plaques and tangles by virtue of tau and/or beta amyloid overexpression, these models do not reflect the fact that in sAD (unlike familial AD) these genes are not risk factors per se and that other mechanisms like oxidative stress, metabolic dysregulation and inflammation play key roles in AD etiology...
2016: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/27884163/chronic-adiponectin-deficiency-leads-to-alzheimer-s-disease-like-cognitive-impairments-and-pathologies-through-ampk-inactivation-and-cerebral-insulin-resistance-in-aged-mice
#16
Roy Chun-Laam Ng, On-Yin Cheng, Min Jian, Jason Shing-Cheong Kwan, Philip Wing-Lok Ho, Kenneth King-Yip Cheng, Patrick Ka Kit Yeung, Lena Lei Zhou, Ruby Lai-Chong Hoo, Sookja Kim Chung, Aimin Xu, Karen Siu-Ling Lam, Koon Ho Chan
BACKGROUND: Insulin resistance is the major pathogenesis underlying type 2 diabetes mellitus (T2DM) and these patients have doubled risk of Alzheimer's disease (AD). Increasing evidence suggests that insulin resistance plays an important role in AD pathogenesis, possibly due to abnormal GSK3β activation, causing intra- and extracellular amyloid-beta (Aβ) accumulation. Adiponectin (APN) is an adipokine with insulin-sensitizing and anti-inflammatory effects. Reduced circulatory APN level is associated with insulin resistance and T2DM...
November 25, 2016: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/27827305/a-new-leptin-mediated-mechanism-for-stimulating-fatty-acid-oxidation-a-pivotal-role-for-sarcolemmal-fat-cd36
#17
Iman Momken, Adrian Chabowski, Ellen Dirkx, Miranda Nabben, Swati S Jain, Jay T McFarlan, Jan F C Glatz, Joost J F P Luiken, Arend Bonen
Leptin stimulates fatty acid oxidation in muscle and heart; but, the mechanism by which these tissues provide additional intracellular fatty acids for their oxidation remains unknown. We examined, in isolated muscle and cardiac myocytes, whether leptin, via AMP-activated protein kinase (AMPK) activation, stimulated fatty acid translocase (FAT/CD36)-mediated fatty acid uptake to enhance fatty acid oxidation. In both mouse skeletal muscle and rat cardiomyocytes, leptin increased fatty acid oxidation, an effect that was blocked when AMPK phosphorylation was inhibited by adenine 9-β-d-arabinofuranoside or Compound C...
January 1, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/27800610/lipocalin-2-ngal-attenuates-autophagy-to-exacerbate-cardiac-apoptosis-induced-by-myocardial-ischemia
#18
Hye Kyoung Sung, Yee Kwan Chan, Meng Han, James Won Suk Jahng, Erfei Song, Eric Danielson, Thorsten Berger, Tak W Mak, Gary Sweeney
Lipocalin-2 (Lcn2; also termed neutrophil gelatinase-associated lipocalin (NGAL)) levels correlate positively with heart failure (HF) yet mechanisms via which Lcn2 contributes to the pathogenesis of HF remain unclear. In this study, we used coronary artery ligation surgery to induce ischemia in wild-type (wt) mice and this induced a significant increase in myocardial Lcn2. We then compared wt and Lcn2 knockout (KO) mice and observed that wt mice showed greater ischemia-induced caspase-3 activation and DNA damage measured by TUNEL than Lcn2KO mice...
August 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27782167/renoprotective-effects-of-metformin-are-independent-of-organic-cation-transporters-1-2-and-amp-activated-protein-kinase-in-the-kidney
#19
Michael Christensen, Jonas B Jensen, Steen Jakobsen, Niels Jessen, Jørgen Frøkiær, Bruce E Kemp, Allison L Marciszyn, Hui Li, Núria M Pastor-Soler, Kenneth R Hallows, Rikke Nørregaard
The type-2 diabetes drug metformin has proven to have protective effects in several renal disease models. Here, we investigated the protective effects in a 3-day unilateral ureteral obstruction (3dUUO) mouse model. Compared with controls, ureteral obstructed animals displayed increased tubular damage and inflammation. Metformin treatment attenuated inflammation, increased the anti-oxidative response and decreased tubular damage. Hepatic metformin uptake depends on the expression of organic cation transporters (OCTs)...
October 26, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27780848/sucrose-nonfermenting-related-kinase-enzyme-mediated-rho-associated-kinase-signaling-is-responsible-for-cardiac-function
#20
Stephanie M Cossette, Vijesh J Bhute, Xiaoping Bao, Leanne M Harmann, Mark A Horswill, Indranil Sinha, Adam Gastonguay, Shabnam Pooya, Michelle Bordas, Suresh N Kumar, Shama P Mirza, Sean P Palecek, Jennifer L Strande, Ramani Ramchandran
BACKGROUND: Cardiac metabolism is critical for the functioning of the heart, and disturbance in this homeostasis is likely to influence cardiac disorders or cardiomyopathy. Our laboratory has previously shown that SNRK (sucrose nonfermenting related kinase) enzyme, which belongs to the AMPK (adenosine monophosphate-activated kinase) family, was essential for cardiac metabolism in mammals. Snrk global homozygous knockout (KO) mice die at postnatal day 0, and conditional deletion of Snrk in cardiomyocytes (Snrk cmcKO) leads to cardiac failure and death by 8 to 10 months...
December 2016: Circulation. Cardiovascular Genetics
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