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https://www.readbyqxmd.com/read/28719670/suppressive-effect-of-amp-activated-protein-kinase-on-the-epithelial-mesenchymal-transition-in-retinal-pigment-epithelial-cells
#1
Ryo Matoba, Yuki Morizane, Yusuke Shiode, Masayuki Hirano, Shinichiro Doi, Shinji Toshima, Ryoichi Araki, Mika Hosogi, Tomoko Yonezawa, Fumio Shiraga
The epithelial-mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells plays a central role in the development of proliferative vitreoretinopathy (PVR). The purpose of this study was to investigate the effect of AMP-activated protein kinase (AMPK), a key regulator of energy homeostasis, on the EMT in RPE cells. In this study, EMT-associated formation of cellular aggregates was induced by co-stimulation of cultured ARPE-19 cells with tumor necrosis factor (TNF)-α (10 ng/ml) and transforming growth factor (TGF)-β2 (5 ng/ml)...
2017: PloS One
https://www.readbyqxmd.com/read/28717968/deletion-of-type-2-cannabinoid-receptor-induces-alzheimer-s-disease-like-tau-pathology-and-memory-impairment-through-ampk-gsk3%C3%AE-pathway
#2
Lin Wang, Bing-Jin Liu, Yun Cao, Wei-Qi Xu, Dong-Sheng Sun, Meng-Zhu Li, Fang-Xiao Shi, Man Li, Qing Tian, Jian-Zhi Wang, Xin-Wen Zhou
Although several studies have shown that type-2 cannabinoid receptor (CB2R) is involved in Alzheimer's disease (AD) pathology, the effects of CB2R on AD-like tau abnormal phosphorylation and its underlying mechanism remain unclear. Herein, we employed the CB2R(-/-) mice as the animal model to explore roles of CB2R in regulating tau phosphorylation and brain function. We found that CB2R(-/-) mice display AD-like tau hyperphosphorylation, hippocampus-dependent memory impairment, increase of GSK3β activity, decrease of AMPK and Sirt1 activity and mitochondria dysfunction...
July 17, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28704996/imidacloprid-promotes-high-fat-diet-induced-adiposity-in-female-c57bl-6j-mice-and-enhance-adipogenesis-in-3t3-l1-adipocytes-via-ampk%C3%AE-mediated-pathway
#3
Quancai Sun, Weipeng Qi, Xiao Xiao, Szu-Hao Yang, Daeyoung Kim, Kyong-Sup Yoon, John M Clark, Yeonhwa Park
Imidacloprid, a neonicotinoid insecticide, has been reported to enhance adipogenesis and resulted in insulin resistance in vitro. It was also reported to promote high fat diet-induced obesity and insulin resistance in male C57BL/6J mice. The current study was to determine the effects of imidacloprid and its interaction with dietary fat in the development of adiposity and insulin resistance in female C57BL/6J mice. Mice were fed with imidacloprid (0.06, 0.6, or 6 mg/kg bw/day) mixed in low fat (4% w/w) or high fat (20% w/w) diet for 12 weeks...
July 13, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28699918/ampk-activation-dependent-autophagy-compromises-oleanolic-acid-induced-cytotoxicity-in-human-bladder-cancer-cells
#4
Yarong Song, Peng Zhang, Yadong Sun, Xuechao Li, Lifeng Chen, Yajun Xiao, Yifei Xing
Autophagy is an evolutionarily conserved catabolic process in eukaryotic cells, which allows cells to overcome a wide array of of stresses and has recently been shown to result in drug resistance. This study examined the effect of autophagy on oleanolic acid (OA)-induced cytotoxicity against bladder cancer cells. Our study demonstrated that OA inhibited cell viability, proliferation, and induced apoptosis in bladder cancer lines T24 and EJ. Furthermore, OA induced autophagy in both cell lines by activating AMP-activated protein kinase (AMPK), inhibiting mechanistic target of rapamycin (mTOR) and promoting unc-51 like autophagy activating kinase 1 (ULK1)...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28689811/ampk-activation-ameliorates-d-galn-lps-induced-acute-liver-failure-by-upregulating-foxo3a-to-induce-autophagy
#5
Yan-Min Liu, Jun Lv, Qing-Lei Zeng, Shen Shen, Ji-Yuan Xing, Ying-Ying Zhang, Zhi-Hao Zhang, Zu-Jiang Yu
BACKGROUND AND AIM: Acute liver failure (ALF) is an uncommon but serious disease still carrying a high mortality. This study aimed to investigate the mechanism of AMPK on D-GalN/LPS-induced ALF. METHODS: In this study, we utilized intraperitoneal injection of D-GalN/LPS to induce ALF model, and analyzed the expression of AMPK, inflammatory cytokines (TNF-α, IL-1β and IL-6), Foxo3A and autophagy-related genes (Atg-5, Beclin-1, Atg-7) by real-time quantitative polymerase chain reaction (RT-PCR) in liver tissue...
July 6, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28683454/interactions-of-tlr4-and-ppar%C3%AE-dependent-on-ampk-signalling-pathway-contribute-to-anti-inflammatory-effects-of-vaccariae-hypaphorine-in-endothelial-cells
#6
Haijian Sun, Xuexue Zhu, Wei Lin, Yuetao Zhou, Weiwei Cai, Liying Qiu
Background /Aims: Accumulating evidence indicates that endothelial inflammation is one of the critical determinants in pathogenesis of atherosclerotic cardiovascular disease. Our previous studies had demonstrated that Vaccariae prevented high glucose or oxidative stress-triggered endothelial dysfunction in vitro. Very little is known about the potential effects of hypaphorine from Vaccariae seed on inflammatory response in endothelial cells. METHODS: In the present study, we evaluated the anti-inflammatory effects of Vaccariae hypaphorine (VH) on lipopolysaccharide (LPS)-challenged endothelial EA...
July 3, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28676953/regulation-of-sirt1-ampk-axis-is-critically-involved-in-gallotannin-induced-senescence-and-impaired-autophagy-leading-to-cell-death-in-hepatocellular-carcinoma-cells
#7
Hee Young Kwon, Ju-Ha Kim, Bonglee Kim, Sanjay K Srivastava, Sung-Hoon Kim
Hepatocellular carcinoma (HCC) is one of the most fatal malignancies with high mortality worldwide. Here the underlying antitumor mechanism of gallotannin was elucidated in HCC cells. Gallotannin suppressed viability and colony formation, increased subG1 portion and also induced senescence via upregulation of p21, G0/G1 arrest and higher SA-β-gal activity in HepG2 and SK-Hep1 cells. However, pan-caspase inhibitor Z-VAD-FMK reversed the ability of gallotannin to activate caspase 3 at 48 h after treatment in two HCC cells...
July 4, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28663724/activation-of-transient-receptor-potential-vanilloid-4-impairs-the-dendritic-arborization-of-newborn-neurons-in-the-hippocampal-dentate-gyrus-through-the-ampk-and-akt-signaling-pathways
#8
Yujing Tian, Mengwen Qi, Zhouqing Wang, Chunfeng Wu, Zhen Sun, Yingchun Li, Sha Sha, Yimei Du, Lei Chen, Ling Chen
Neurite growth is an important process for the adult hippocampal neurogenesis which is regulated by a specific range of the intracellular free Ca(2+) concentration ([Ca(2+)]i). Transient receptor potential vanilloid 4 (TRPV4) is a calcium-permeable channel and activation of it causes an increase in [Ca(2+)]i. We recently reported that TRPV4 activation promotes the proliferation of stem cells in the adult hippocampal dentate gyrus (DG). The present study aimed to examine the effect of TRPV4 activation on the dendrite morphology of newborn neurons in the adult hippocampal DG...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28656194/excessive-nnos-no-ampk-signaling-activation-mediated-by-the-blockage-of-the-cbs-h2s-system-contributes-to-oxygen%C3%A2-glucose-deprivation%C3%A2-induced-endoplasmic-reticulum-stress-in-pc12%C3%A2-cells
#9
Rui Zhang, Yong-Quan Lin, Wei-Sheng Wang, Xin-Qiang Wang
Hypoxic‑ischemia stress causes severe brain injury, leading to death and disability worldwide. Although it has been reported that endoplasmic reticulum (ER) stress is an essential step in the progression of hypoxia or ischemia‑induced brain injury, the underlying molecular mechanisms are and have not yet been fully elucidated. Accumulating evidence has indicated that both nitric oxide (NO) and hydrogen sulfide (H2S) play an important role in the development of cerebral ischemic injury. In the present study, we aimed to investigate the effect of the association between NO signaling and the cystathionine β‑synthase (CBS)/H2S system on ER stress in a cell model of cerebral hypoxia‑ischemia injury...
June 21, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28653238/ampk-nf-%C3%AE%C2%BAb-signaling-pathway-regulated-by-ghrelin-participates-in-the-regulation-of-huvec-and-thp1-inflammation
#10
Min Zhang, Shuping Wang, Zhicheng Pan, Tiantong Ou, Jianwei Ma, Hua Liu, Ruogu Li, Ping Yang, Wenzheng Han, Shaofeng Guan, Xumin Hou, Weiyi Fang, Xinkai Qu
Endothelial inflammation and monocyte plays an essential role in the initiation and progression of atherosclerosis. Ghrelin is beneficial for atherosclerosis progression. However, the detailed and precise molecular mechanisms of how ghrelin regulates endothelial inflammation are not clear. In this study, we investigated the regulation mechanism of ghrelin on TNF-α-activated endothelial inflammation and monocyte adhesion. It was found that TNF-α-induced monocyte adhesion on HUVEC was significantly attenuated by ghrelin...
June 26, 2017: Molecular and Cellular Biochemistry
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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