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https://www.readbyqxmd.com/read/28624657/adiponectin-improves-the-osteointegration-of-titanium-implant-under-diabetic-conditions-by-reversing-mitochondrial-dysfunction-via-the-ampk-pathway-in-vivo-and-in-vitro
#1
Xiao-Fan Hu, Lin Wang, Yi-Zhao Lu, Geng Xiang, Zi-Xiang Wu, Ya-Bo Yan, Yang Zhang, Xiong Zhao, Yuan Zang, Lei Shi, Wei Lei, Ya-Fei Feng
Diabetes-induced reactive oxygen species (ROS) overproduction would result in compromised osteointegration of titanium implant (TI) and high rate of implant failure, yet the underlying mechanisms remain elusive. Adiponectin (APN) is a fat-derived adipocytokine with strong antioxidant, mitochondrial-protective and anti-diabetic efficacies. We hypothesized that mitochondrial dysfunction under diabetes may account for the oxidative stress in osteoblasts and titanium-bone interface (TBI) instability, which could be ameliorated by APN...
June 14, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28619845/the-prohibitin-binding-compound-fluorizoline-induces-apoptosis-in-chronic-lymphocytic-leukemia-cells-through-the-upregulation-of-noxa-and-synergizes-with-ibrutinib-aicar-or-venetoclax
#2
Ana M Cosialls, Helena Pomares, Daniel Iglesias-Serret, José Saura-Esteller, Sonia Núñez-Vázquez, Diana M González-Gironès, Esmeralda de la Banda, Sara Preciado, Fernando Albericio, Rodolfo Lavilla, Gabriel Pons, Eva M González-Barca, Joan Gil
Fluorizoline is a new synthetic molecule that induces apoptosis by selectively targeting prohibitins. In this study, the pro-apoptotic effect of fluorizoline was assessed in 34 primary samples from patients with chronic lymphocytic leukemia. Fluorizoline induced apoptosis in chronic lymphocytic leukemia cells at concentrations in the low micromolar range. All primary samples were sensitive to fluorizoline irrespectively of patients' clinical or genetic features, whereas normal T lymphocytes were less sensitive...
June 15, 2017: Haematologica
https://www.readbyqxmd.com/read/28618992/modulating-mitophagy-in-mitochondrial-disease
#3
Eszter Dombi, Heather Mortiboys, Joanna Poulton
Mitochondrial diseases may result from mutations in the maternally-inherited mitochondrial DNA (mtDNA) or from mutations in nuclear genes encoding mitochondrial proteins. Their bi-genomic nature makes mitochondrial diseases a very heterogeneous group of disorders that can present at any age and can affect any type of tissue. The autophagic-lysosomal degradation pathway plays an important role in clearing dysfunctional and redundant mitochondria through a specific quality control mechanism termed mitophagy. Mitochondria could be targeted for autophagic degradation for a variety of reasons including basal turnover for recycling, starvation induced degradation, and degradation due to damage...
June 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28611100/ampk-activation-enhances-the-anti-atherogenic-effects-of-high-density-lipoproteins-in-apoe-mice
#4
Ang Ma, Jing Wang, Liu Yang, Yuanyuan An, Haibo Zhu
HDL plays crucial roles at multiple stages of the pathogenesis of atherosclerosis. AMP-activated protein kinase (AMPK) is a therapeutic candidate for the treatment of cardiovascular disease. However, the effect of AMPK activation on HDL functionality has not been established in vivo. We assessed the effects of pharmacological AMPK activation using A-769662, AICAR, metformin, and IMM-H007 on the atheroprotective functions of HDL in apoE-deficient (apoE-/-) mice fed with a high fat diet. After administration, although there no changes in serum lipid levels among the groups...
June 13, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28593136/amp-activated-protein-kinase-regulates-lipid-metabolism-and-the-fibrotic-phenotype-of-hepatic-stellate-cells-through-inhibition-of-autophagy
#5
Ming Chen, Jiaxing Liu, Lili Yang, Wenhua Ling
Hepatic stellate cells (HSCs) are the principal hepatic cell type responsible for liver fibrosis. Although AMP-activated protein kinase (AMPK) is known to regulate the activation of HSCs, little is known about its underlying molecular mechanisms. In the present study, we demonstrate that AMPK activation by 5-aminoimidazole-4-carboxamide-1-4-ribofuranoside (AICAR) restricts the fibrotic potential elicited by transforming growth factor β (TGF-β) in LX-2 cells through modulation of autophagy. AICAR treatment activated the mechanistic target of rapamycin/Akt pathway and thus inhibited autophagy flux and lipid droplet degradation in lysosomes induced by TGF-β...
June 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28565878/ginsenoside-rb3-strengthens-the-hypoglycemic-effect-through-ampk-for-inhibition-of-hepatic-gluconeogenesis
#6
Fanli Meng, Xiaotian Su, Wei Li, Yinan Zheng
Ginsenoside Rb3 is one of the major active components in protopanaxdiol type ginsenosides, and has demonstrated anti-diabetic activity. However, the mechanism of this action has yet to be elucidated. The present study investigated the effects of ginsenoside Rb3 on the AMP-activated protein kinase (AMPK) gluconeogenesis pathway. The present study involved the use of HepG2 cells and western blot analysis to systematically evaluate the effect of ginsenoside Rb3 on AMPK signaling proteins and key factors of gluconeogenesis [phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase, forkhead transcription factor 1 (FOXO1) and hepatic nuclear receptor 4α (HNF4α)]...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28556920/ampk-activator-acadesine-fails-to-alleviate-isoniazid-caused-mitochondrial-instability-in-hepg2-cells
#7
Tian-Guang Zhang, Takashi Ikejima, Toshihiko Hayashi, Jun Zhao, Yi-Mei Wang, Shuang-Qing Peng
Isoniazid (INH) is a first-line antituberculosis drug that is adversely associated with hepatotoxicity. Recently, impairment of mitochondrial homeostasis involved in this side effect has been noticed. Mitochondrial homeostasis is achieved by the balance between the generation of functional mitochondria by biogenesis and elimination of dysfunctional mitochondria by autophagy. AMP-activated protein kinase (AMPK) can maintain mitochondrial stability through positive control of these two processes. In this study, we showed that AMPK activator acadesine (AICAR) alleviated INH-caused impairment of mitochondrial biogenesis by activation of silent information regulator two ortholog 1 (SIRT1)-peroxisome proliferator-activated receptor γ coactivator 1α (PGC1 α) pathway in HepG2 cells...
May 29, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28534814/autophagy-regulates-proteasome-inhibitor-induced-pigmentation-in-human-embryonic-stem-cell-derived-retinal-pigment-epithelial-cells
#8
Kati Juuti-Uusitalo, Ali Koskela, Niko Kivinen, Johanna Viiri, Juha M T Hyttinen, Mika Reinisalo, Arto Koistinen, Hannu Uusitalo, Debasish Sinha, Heli Skottman, Kai Kaarniranta
The impairment of autophagic and proteasomal cleansing together with changes in pigmentation has been documented in retinal pigment epithelial (RPE) cell degeneration. However, the function and co-operation of these mechanisms in melanosome-containing RPE cells is still unclear. We show that inhibition of proteasomal degradation with MG-132 or autophagy with bafilomycin A1 increased the accumulation of premelanosomes and autophagic structures in human embryonic stem cell (hESC)-derived RPE cells. Consequently, upregulation of the autophagy marker p62 (also known as sequestosome-1, SQSTM1) was confirmed in Western blot and perinuclear staining...
May 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28496098/combined-treatment-with-metformin-and-2-deoxy-glucose-induces-detachment-of-viable-mda-mb-231-breast-cancer-cells-in-vitro
#9
Maruša Bizjak, Petra Malavašič, Klemen Dolinar, Jelka Pohar, Sergej Pirkmajer, Mojca Pavlin
Triple naegative breast cancer has an increased rate of distant metastasis and consequently poor prognosis. To metastasize, breast cancer cells must detach from the main tumour mass and resist anoikis, a programmed cell death induced by lack of cell-extracellular matrix communication. Although cancer cells must detach to metastasize in vivo, the viability of floating cancer cells in vitro is rarely investigated. Here we show that co-treatment of anoikis-resistant MDA-MB-231 cells with metformin and 2-deoxy-D-glucose (2-DG) increased the percentage of floating cells, of which about 95% were viable...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28494020/pannexin-3-regulates-proliferation-and-differentiation-of-odontoblasts-via-its-hemichannel-activities
#10
Tsutomu Iwamoto, Takashi Nakamura, Masaki Ishikawa, Keigo Yoshizaki, Asuna Sugimoto, Hiroko Ida-Yonemochi, Hayato Ohshima, Masahiro Saito, Yoshihiko Yamada, Satoshi Fukumoto
Highly coordinated regulation of cell proliferation and differentiation contributes to the formation of functionally shaped and sized teeth; however, the mechanism underlying the switch from cell cycle exit to cell differentiation during odontogenesis is poorly understood. Recently, we identified pannexin 3 (Panx3) as a member of the pannexin gap junction protein family from tooth germs. The expression of Panx3 was predominately localized in preodontoblasts that arise from dental papilla cells and can differentiate into dentin-secreting odontoblasts...
2017: PloS One
https://www.readbyqxmd.com/read/28485811/the-effects-of-second-messenger-camp-and-its-relative-components-on-the-contraction-of-uterine-smooth-muscle-of-rat
#11
S-J Shu, X-G Lei, J-H Liang, Y-H Song, Q Xu, X-D Chen, L-G Mao, Z-G Li
OBJECTIVE: To investigate the effect of second messenger pathways on the uterine smooth muscle contraction and their associated mechanisms, and compare the evaluation methods. MATERIALS AND METHODS: Preparation of uterine smooth muscle strips from healthy pregnant 18-21 d SD and non-pregnant rats. When the contraction of muscle strips was stable, we conducted gradient administration: PDE4 inhibitors (Z90), prostaglandin PGE2, adenylate cyclase inhibitor (SQ 22,530), cAMP analogs (dbcAMP) and AMPK agonists (AICAR), solvent dimethyl sulfoxide (DMSO) as controlled...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28481450/novel-regulation-of-melanogenesis-by-adiponectin-via-the-ampk-crtc-pathway
#12
Seunghyun Bang, Kwang Hee Won, Hye-Rim Moon, Hanju Yoo, Areum Hong, Youngsup Song, Sung Eun Chang
Several studies observed that adiponectin, an important adipokine that improves glucose metabolism by regulating AMP-activated protein kinase (AMPK) signaling, is dermatologically beneficial. In our recent microarray data, we found that adiponectin expression was lower in lesional skin than in non-lesional skin of melasma patients. Given that AMPK is a key adiponectin signaling mediator, we investigated the role of adiponectin and AICAR, a cell-permeable AMPK activator, in melanogenesis. We herein showed that adiponectin and AICAR downregulated MITF, tyrosinase, TRP-1, and DCT expression and reduced melanin content in normal human and mouse melanocytes...
May 8, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28479394/ampk-contributes-to-aerobic-exercise-induced-antinociception-downstream-of-endocannabinoids
#13
Tanya S King-Himmelreich, Christine V Möser, Miriam C Wolters, Julia Schmetzer, Yannik Schreiber, Nerea Ferreirós, Otto Q Russe, Gerd Geisslinger, Ellen Niederberger
Physical exercise has been repeatedly associated with decreased nociceptive responses but the underlying mechanisms have still not been fully clarified. In this study, we investigated exercise-induced effects after a single bout of treadmill running on the mouse model of formalin-induced inflammatory nociception. As potential molecular mediators, we focused on endogenous endocannabinoids as well as AMP-activated protein kinase (AMPK). Our results showed that wild type mice display a reduced nociceptive response in the formalin test after treadmill running, while exercise had no effect on inflammatory nociception in AMPKα2 knockout mice...
May 4, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28473772/lack-of-effects-of-metformin-and-aicar-chronic-infusion-on-the-development-of-hypertension-in-dahl-salt-sensitive-rats
#14
Tengis S Pavlov, Vladislav Levchenko, Daria V Ilatovskaya, Hui Li, Oleg Palygin, Nuria M Pastor-Soler, Kenneth R Hallows, Alexander Staruschenko
In the kidney, reabsorption via the epithelial sodium channel (ENaC) is involved in long-term blood pressure control. Previously we demonstrated that ENaC hyperactivity is associated with development of salt-sensitive (SS) hypertension in Dahl SS rats. AMP-activated kinase (AMPK), playing a role in cellular energy homeostasis, has been shown to decrease ENaC activity. Here, we tested whether metformin and AICAR, two drugs that activate AMPK, affect the development of salt-induced hypertension. High salt diet significantly increased mean arterial pressure (MAP) in Dahl SS rats...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28455001/the-influence-of-aicar-direct-activator-of-amp-activated-protein-kinase-ampk-on-liver-proteome-in-apoe-knockout-mice
#15
Maciej Suski, Anna Wiśniewska, Aneta Stachowicz, Rafał Olszanecki, Katarzyna Kuś, Magdalena Białas, Józef Madej, Ryszard Korbut
There is a growing body of evidence that altered functioning of apoE may aggravate cellular energy homeostasis and stress response, leading to oxidative stress, mitochondrial dysfunction, endoplasmic reticulum (ER) stress and inflammation, leading to hypercholesterolemia, dyslipidemia, liver steatosis and neurodegeneration. One of the key cellular responses to mitochondria and ER-stress related processes and cellular energy imbalance is AMP-activated protein kinase (AMPK), considered as a cellular master energy sensor and critical regulator of mitochondrial homeostasis...
April 26, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28445821/the-ampk-mtor-pathway-is-involved-in-d-dopachrome-tautomerase-gene-transcription-in-adipocytes-differentiated-from-sgbs-cells-a-human-preadipocyte-cell-line
#16
Takeo Iwata, Kyoko Kuribayashi, Masahiko Nakasono, Noriko Saito-Tarashima, Noriaki Minakawa, Noriko Mizusawa, Rie Kido, Katsuhiko Yoshimoto
In adipose tissue, D-dopachrome tautomerase (DDT), a cytokine with structural similarity to macrophage migration inhibitory factor, is mainly expressed in adipocytes rather than preadipocytes and acts as an anti-obesity adipokine in an autocrine manner. However, its transcriptional regulation is largely unknown. In order to explore molecules affecting DDT transcription, a chemical library screening using HEK293 cells stably expressing a DDT promoter-reporter construct was performed. Several derivatives of 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR), an AMP-activated protein kinase (AMPK) activator, were identified as transcriptional activators of the DDT gene...
April 23, 2017: Cytokine
https://www.readbyqxmd.com/read/28435970/-amp-activated-kinase-activation-inhibits-transforming-growth-factor-%C3%AE-1-production-in-cardiac-fibroblasts-via-targeting-c-ebp%C3%AE
#17
Han Xiao, Cheng-Shi Piao, Rui-Fei Chen, You-Yi Zhang
AMP-activated protein kinase (AMPK) activation has been shown to protect against fibrosis. However, the underlying mechanism remains unclear. Here we explored the effect of AMPK activation on transforming growth factor-β1 (TGFβ1) production induced by angiotensin II (AngII) in cardiac fibroblasts and the underlying mechanisms. Adult mouse cardiac fibroblasts were isolated. TGFβ1 and AMPK activity were determined by ELISA and Western blots, respectively. Pretreatment of AMPK activator AICAR inhibited TGFβ1 production induced by AngII in cardiac fibroblasts, which was reversed by AMPK inhibitor compound C...
April 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28432301/ampk-signaling-in-the-nucleus-accumbens-core-mediates-cue-induced-reinstatement-of-cocaine-seeking
#18
Xue-Jiao Gao, Kai Yuan, Lu Cao, Wei Yan, Yi-Xiao Luo, Min Jian, Jian-Feng Liu, Qin Fang, Ji-Shi Wang, Ying Han, Jie Shi, Lin Lu
Relapse to drug seeking can be caused by exposure to drug-associated cues, provoking drug craving even after prolonged abstinence. Recent studies demonstrated that AMP-activated protein kinase (AMPK) regulates neuronal morphology and membrane excitability in neurons. Here, we investigated the role of AMPK activity in the nucleus accumbens (NAc) in relapse to cocaine seeking. We found that exposure to drug-related cues reinstated cocaine-seeking behavior and increased AMPK and p70s6k phosphorylation in the NAc core but not shell...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28409163/pgc1%C3%AE-activators-mitigate-diabetic-tubulopathy-by-improving-mitochondrial-dynamics-and-quality-control
#19
So-Young Lee, Jun Mo Kang, Dong-Jin Kim, Seon Hwa Park, Hye Yun Jeong, Yu Ho Lee, Yang Gyun Kim, Dong Ho Yang, Sang Ho Lee
Purpose. In this study, we investigated the effect of PGC1α activators on mitochondrial fusion, fission, and autophagic quality control in renal tubular cells in a diabetic environment in vivo and in vitro. We also examined whether the upregulation of PGC1α attenuates diabetic tubulopathy by normalizing mitochondrial homeostasis. Methods. HKC8 cells were subjected to high-glucose conditions (30 mM D-glucose). Diabetes was induced with streptozotocin (STZ, 50 mg/kg i.p. for 5 days) in male C57/BL6J mice...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28407446/doping-control-study-of-aicar-in-postrace-urine-and-plasma-samples-from-horses
#20
Jenny K Y Wong, Wai Him Kwok, George H M Chan, Timmy L S Choi, Emmie N M Ho, Murielle Jaubert, Ludovic Bailly-Chouriberry, Yves Bonnaire, Adam Cawley, H Ming Williams, John Keledjian, Lydia Brooks, Adam Chambers, Yuanyuan Lin, Terence S M Wan
Acadesine, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, commonly known as AICAR, is a naturally occurring adenosine monophosphate-activated protein kinase (AMPK) activator in many mammals including humans and horses. AICAR has attracted considerable attention recently in the field of doping control due to a study showing enhancement of endurance performance in unexercised or untrained mice, resulting in the term "exercise pill". Its use has been classified as gene doping by the World Anti-Doping Agency (WADA), and since it is endogenous, it may only be possible to control deliberate administration of AICAR to racehorses after establishment of an appropriate threshold...
April 13, 2017: Drug Testing and Analysis
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