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AMPK AND bone

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https://www.readbyqxmd.com/read/29749459/ctrp9-ameliorates-cellular-senescence-via-pgc%C3%A2-1%C3%AE-ampk-signaling-in-mesenchymal-stem-cells
#1
Qun Li, Zhangzhang Zhu, Chengde Wang, Lin Cai, Jianglong Lu, Yongchun Wang, Jiadong Xu, Zhipeng Su, Weiming Zheng, Xianbin Chen
Stroke is the second most common cause of death worldwide, and thus, it imposes great financial burdens on both individuals and society. Mesenchymal stem cell (MSC) therapy is a promising approach for ischemic brain injury. However, MSC treatment potential is progressively reduced with age, limiting their therapeutic efficacy for brain repair post‑stroke. C1q and tumor necrosis factor‑related protein 9 (CTRP9) is a novel cytoprotective cytokine with antioxidant effects, which is highly expressed in brain tissue...
May 9, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29721581/glycyrrhizin-suppresses-rankl-induced-osteoclastogenesis-and-oxidative-stress-through-inhibiting-nf-%C3%AE%C2%BAb-and-mapk-and-activating-ampk-nrf2
#2
Zhikun Li, Chao Chen, Xiaodong Zhu, Yifan Li, Ronghua Yu, Wei Xu
The treatment for osteoporosis involves inhibiting bone resorption and osteoclastogenesis. Glycyrrhizin (GLY) is a triterpenoid saponin glycoside known to be as the most medically efficacious component of the licorice plant. It has strong anti-inflammatory, antioxidant, and antitumor properties. We investigated the effect of GLY on osteoclastogenesis, bone resorption, and intracellular oxidative stress and its molecular mechanisms. In vitro osteoclastogenesis assays were performed using bone marrow monocytes with and without glycyrrhizin...
May 2, 2018: Calcified Tissue International
https://www.readbyqxmd.com/read/29674003/tanshinone-iia-suppresses-fc%C3%AE%C2%B5ri-mediated-mast-cell-signaling-and-anaphylaxis-by-activation-of-the-sirt1-lkb1-ampk-pathway
#3
Xian Li, Soon Jin Park, Fansi Jin, Yifeng Deng, Ju Hye Yang, Jae-Hoon Chang, Dong-Young Kim, Jung-Ae Kim, Youn Ju Lee, Makoto Murakami, Kun Ho Son, Hyeun Wook Chang
AMP-activated protein kinase (AMPK) and its upstream mediators liver kinase B1 (LKB1) and sirtuin 1 (Sirt1) are generally known as key regulators of metabolism. We have recently reported that the AMPK pathway negatively regulates mast cell activation and anaphylaxis. Tanshinone IIA (Tan IIA), an active component of Salvia miltiorrhiza extract that is currently used for the treatment of cardiovascular and cerebrovascular diseases, shows anti-diabetic activity and improves insulin resistance in db/db mice through activation of AMPK...
April 16, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29649480/high-glucose-downregulates-the-effects-of-autophagy-on-osteoclastogenesis-via-the-ampk-mtor-ulk1-pathway
#4
Zhen-Yu Cai, Bo Yang, Ying-Xu Shi, Wei-Lin Zhang, Fei Liu, Wei Zhao, Mao-Wei Yang
Diabetes is a chronic disease that disrupts the balance between bone formation and bone desorption, which can lead to osteoporosis, increasing the risk of fracture. However, compared with osteoblasts, the biological effects of hyperglycemia on osteoclastogenesis remain to be elucidated. Therefore, we investigated the impact of glucose at different concentrations (5.5, 10.5, 15.5, 20.5, 25.5, and 30.5 mM) on osteoclastogenesis using RAW264.7 cells. Cell proliferation was measured with the cell counting kit-8 assay, and osteoclastogenesis was detected with tartrate-resistant acid phosphatase staining and bone resorption assays, as well as protein cathepsin K expression...
April 9, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29555409/functional-organic-cation-transporters-mediate-osteogenic-response-to-metformin-in-human-umbilical-cord-mesenchymal-stromal-cells
#5
Faisal E Al Jofi, Tao Ma, Dong Guo, Monica P Schneider, Yan Shu, Hockin H K Xu, Abraham Schneider
BACKGROUND: Compelling evidence indicates that metformin, a low-cost and safe orally administered biguanide prescribed to millions of type 2 diabetics worldwide, induces the osteoblastic differentiation of mesenchymal stromal cells (MSCs) through the 5' adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway. As a highly hydrophilic cationic compound, metformin uptake is facilitated by cell membrane organic cation transporters (OCTs) of the solute carrier 22A gene family...
March 16, 2018: Cytotherapy
https://www.readbyqxmd.com/read/29522773/effects-of-ovariectomy-and-exercise-training-intensity-on-energy-substrate-and-hepatic-lipid-metabolism-and-spontaneous-physical-activity-in-mice
#6
Marc A Tuazon, Sara C Campbell, Dylan J Klein, Sue A Shapses, Keith R Anacker, Tracy G Anthony, Mehmet Uzumcu, Gregory C Henderson
BACKGROUND: Menopause is associated with fatty liver, glucose dysregulation, increased body fat, and impaired bone quality. Previously, it was demonstrated that single sessions of high-intensity interval exercise (HIIE) are more effective than distance- and duration-matched continuous exercise (CE) on altering hepatic triglyceride (TG) metabolism and very-low density lipoprotein-TG (VLDL-TG) secretion. METHODS: Six weeks training using these modalities was examined for effects on hepatic TG metabolism/secretion, glucose tolerance, body composition, and bone mineral density (BMD) in ovariectomized (OVX) and sham-operated (SHAM) mice...
March 6, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29484369/amp-activated-protein-kinase-stimulates-osteoblast-differentiation-and-mineralization-through-autophagy-induction
#7
Yi Li, Jiajia Su, Wenchao Sun, Lin Cai, Zhouming Deng
Previous studies have reported that adenosine monophosphate‑activated protein kinase (AMPK) activation can enhance osteoblast differentiation and mineralization; however, the underlying mechanism is not fully understood. Autophagy also serves an important role in osteoblast mineralization and bone homeostasis. The present study aimed to explore whether activation of AMPK could enhance osteoblast differentiation and mineralization via the induction of autophagy. The fracture healing and nonunion animal models were established and verified by X-ray imaging...
May 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29480499/evaluating-the-role-of-host-ampk-in-leishmania-burden
#8
Diana Moreira, Jérôme Estaquier, Anabela Cordeiro-da-Silva, Ricardo Silvestre
The study of host AMP-activated protein kinase (AMPK) activation during Leishmania infection imposes distinct types of techniques to measure protein expression and activation, as well as to quantify, at transcription and translational levels, its downstream targets. The investigation of host AMPK protein modulation during Leishmania infection should primarily be assessed during in vitro infections using as a host murine bone marrow-derived macrophages (BMMos). The infection outcome is assessed measuring the percentage of infected cells in the context of BMMos...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29477034/alpinumisoflavone-rescues-glucocorticoid-induced-apoptosis-of-osteocytes-via-suppressing-nox2-dependent-ros-generation
#9
Jun Yin, Leixiang Han, Wei Cong
BACKGROUND: Long term use of glucocorticoids is one of the most common causes of secondary osteoporosis. Osteocyte, the most abundant cell type in bone, coordinates the function of osteoblast and osteoclast. This study evaluates the protective effect of alpinumisoflavone (AIF), a naturally occurring flavonoid compound, on dexamethasone (Dex)-induced apoptosis of osteocytes. METHODS: MLO-Y4 cell was used as a cell model. The effect of AIF on the cell viability was assessed by MTT assay...
April 2018: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29474739/mst1-2-kinases-modulate-glucose-uptake-for-osteoblast-differentiation-and-bone-formation
#10
Wenling Li, Yujie Deng, Bo Feng, Kingston King-Lun Mak
Bone formation and bone homeostasis are energy-expensive processes. How they are being regulated by energy needs is not completely understood. This is of high clinical importance because diabetic-induced bone loss is common whereas the underlying mechanisms are unclear. Here, we show that Mst1/2 are important regulators for glucose uptake during osteoblast differentiation. Genetically removal of both Mst1/2 kinases simultaneously in mice in early and mature osteoblasts inhibits bone formation and bone remodeling, respectively...
February 23, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29452207/glycogen-synthase-kinase-3%C3%AE-promotes-liver-innate-immune-activation-by-restraining-amp-activated-protein-kinase-activation
#11
Haoming Zhou, Han Wang, Ming Ni, Shi Yue, Yongxiang Xia, Ronald W Busuttil, Jerzy W Kupiec-Weglinski, Ling Lu, Xuehao Wang, Yuan Zhai
BACKGROUND & AIMS: Glycogen synthase kinase 3β (Gsk3β [Gsk3b]) is a ubiquitously expressed kinase with distinctive functions in different types of cells. Although its roles in regulating innate immune activation and ischaemia and reperfusion injuries (IRIs) have been well documented, the underlying mechanisms remain ambiguous, in part because of the lack of cell-specific tools in vivo. METHODS: We created a myeloid-specific Gsk3b knockout (KO) strain to study the function of Gsk3β in macrophages in a murine liver partial warm ischaemia model...
February 13, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29413962/homocysteine-causes-dysfunction-of-chondrocytes-and-oxidative-stress-through-repression-of-sirt1-ampk-pathway-a-possible-link-between-hyperhomocysteinemia-and-osteoarthritis
#12
Ching-Hou Ma, Yen Chun Chiua, Chin-Hsien Wu, I-Ming Jou, Yuan-Kun Tu, Ching-Hsia Hung, Pei-Ling Hsieh, Kun-Ling Tsai
Emerging evidence has indicated that the perturbed expression of homocysteine (Hcy) may induce mitochondrial dysfunction and disturb bone metabolism. Sirtuin 1 (SIRT1) and AMP-activated protein kinase (AMPK) are two critical sensors that regulate mitochondrial biogenesis and have been recognized as therapeutic targets in osteoarthritis (OA). This study was designed to test whether Hcy caused pro-osteoarthritic changes through modulation of SIRT1 and AMPK. Our results showed that administration of Hcy reduced the SIRT1/AMPK/PGC-1α signaling in chondrocytes, leading to mitochondrial dysfunction as a result of increased oxidative stress and apoptosis...
May 2018: Redox Biology
https://www.readbyqxmd.com/read/29374060/-s-glutathionylation-of-estrogen-receptor-%C3%AE-affects-dendritic-cell-function
#13
Jie Zhang, Zhi-Wei Ye, Wei Chen, Yefim Manevich, Shikhar Mehrotra, Lauren Ball, Yvonne Janssen-Heininger, Kenneth D Tew, Danyelle M Townsend
Glutathione S -transferase Pi (GSTP) is a thiolase that catalyzes the addition of glutathione (GSH) to receptive cysteines in target proteins, producing an S -glutathionylated residue. Accordingly, previous studies have reported that S -glutathionylation is constitutively decreased in cells from mice lacking GSTP ( Gstp1 / p2 -/- ). Here, we found that bone marrow-derived dendritic cells (BMDDCs) from Gstp1 / p2 -/- mice have proliferation rates that are greater than those in their WT counterparts ( Gstp1 / p2 +/+ )...
March 23, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29353038/cereblon-crbn-deletion-reverses-streptozotocin-induced-diabetic-osteoporosis-in-mice
#14
Cong Yao, Xiong Guo, Wan-Xia Yao, Chun Zhang
Diabetes mellitus is a major cause to induce osteoporosis. Though the pathogenesis of osteoporosis progression has been well investigated, its still not fully understood. Recently, cereblon (CRBN) was considered as a negative modulator of adenosine monophosphate-activated protein kinase (AMPK) in vitro and in vivo. Here, we presented results indicating that CRBN could effectively regulate osteoporosis development. In STZ-induced wild type (WT) mice with diabetes, the osteoclasts were highly increased along with the deterioration of bone structure...
February 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29338075/liver-kinase-b1-amp-activated-protein-kinase-mediated-regulation-by-gentiopicroside-ameliorates-p2x7-receptor-dependent-alcoholic-hepatosteatosis
#15
Xia Li, Yu Zhang, Quan Jin, Kai-Li Xia, Min Jiang, Ben-Wen Cui, Yan-Ling Wu, Shun-Zong Song, Li-Hua Lian, Ji-Xing Nan
BACKGROUND AND PURPOSE: Regulating P2X7 receptor-mediated activation of NLRP3 inflammasomes could be a therapeutic strategy to treat alcoholic hepatosteatosis. We investigated whether this process was modulated by gentiopicroside, the main active secoiridoid glycoside from Gentiana manshurica Kitagawa. EXPERIMENTAL APPROACH: In vivo models of acute and chronic alcoholic hepatosteatosis were established by intragastrically administered ethanol or using chronic plus binge ethanol feeding of Lieber-DeCarli liquid diet to male C57BL/6 mice...
May 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29324976/ginsenoside-rg1-inhibits-apoptosis-by-increasing-autophagy-via-the-ampk-mtor-signaling-in-serum-deprivation-macrophages
#16
Ping Yang, Lu Ling, Wenjing Sun, Junquan Yang, Ling Zhang, Guoji Chang, Jiazhi Guo, Jun Sun, Lin Sun, Di Lu
Ginsenoside Rg1 (Rg1) has been widely used in a broad range of cardiovascular and cerebral-vascular diseases because of its unique therapeutic properties. However, the underlying mechanisms of Rg1 in the treatment of atherosclerosis have not been fully explored. This study sought to determine the precise molecular mechanisms on how Rg1 might be involved in regulating apoptosis in serum deprivation-induced Raw264.7 macrophages and primary bone marrow-derived macrophages. Results demonstrated that Rg1 treatment effectively suppressed apoptosis and the expression of phosphorylation level of mTOR induced by serum deprivation in Raw264...
February 1, 2018: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29278309/monotropein-promotes-angiogenesis-and-inhibits-oxidative-stress-induced-autophagy-in-endothelial-progenitor-cells-to-accelerate-wound-healing
#17
Chenggui Wang, Cong Mao, Yiting Lou, Jianxiang Xu, Qingqing Wang, Zengjie Zhang, Qian Tang, Xiaolei Zhang, Huazi Xu, Yongzeng Feng
Attenuating oxidative stress-induced damage and promoting endothelial progenitor cell (EPC) differentiation are critical for ischaemic injuries. We suggested monotropein (Mtp), a bioactive constituent used in traditional Chinese medicine, can inhibit oxidative stress-induced mitochondrial dysfunction and stimulate bone marrow-derived EPC (BM-EPC) differentiation. Results showed Mtp significantly elevated migration and tube formation of BM-EPCs and prevented tert-butyl hydroperoxide (TBHP)-induced programmed cell death through apoptosis and autophagy by reducing intracellular reactive oxygen species release and restoring mitochondrial membrane potential, which may be mediated viamTOR/p70S6K/4EBP1 and AMPK phosphorylation...
March 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29250169/therapeutic-strategies-against-cancer-stem-cells-in-human-colorectal-cancer
#18
Magdalena Szaryńska, Agata Olejniczak, Jarosław Kobiela, Piotr Spychalski, Zbigniew Kmieć
Colorectal cancer (CRC) is the third most frequent malignancy and represents the fourth most common cause of cancer-associated mortalities in the world. Despite many advances in the treatment of CRC, the 5-year survival rate of patients with CRC remains unsatisfactory due to tumor recurrence and metastases. Recently, cancer stem cells (CSCs), have been suggested to be responsible for the initiation and relapse of the disease, and have been identified in CRC. Due to their basic biological features, which include self-renewal and pluripotency, CSCs may be novel therapeutic targets for CRC and other cancer types...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29249772/inhibition-of-adenosine-monophosphate-activated-protein-kinase-suppresses-bone-morphogenetic-protein-2-induced-mineralization-of-osteoblasts-via-smad-independent-mechanisms
#19
Ayumu Takeno, Ippei Kanazawa, Masakazu Notsu, Ken-Ichiro Tanaka, Toshitsugu Sugimoto
Previous studies showed that adenosine monophosphate-activated protein kinase (AMPK), which plays as an intracellular energy sensor, promotes the differentiation and mineralization of osteoblasts via enhancing expression of bone morphogenetic protein (BMP)-2, which is a potent inducer of osteoblastogenesis. Thus, the aim of this study was to examine the roles of AMPK in BMP-2-induced osteoblastogenesis. We used a murine osteoblastic cell line MC3T3-E1 and a murine marrow stromal cell line ST2. BMP-2 (50 and 100 ng/mL) stimulated alkaline phosphatase (ALP) activity and enhanced mineralization of MC3T3-E1 cells, while the effects of BMP-2 were partly abolished by an inhibitor of AMPK, ara-A (0...
December 16, 2017: Endocrine Journal
https://www.readbyqxmd.com/read/29246951/metformin-mediates-protection-against-legionella-pneumonia-through-activation-of-ampk-and-mitochondrial-reactive-oxygen-species
#20
Chiaki Kajiwara, Yu Kusaka, Soichiro Kimura, Tetsuo Yamaguchi, Yuta Nanjo, Yoshikazu Ishii, Heiichiro Udono, Theodore J Standiford, Kazuhiro Tateda
In Legionella pneumophila infection, macrophages play a critical role in the host defense response. Metformin, an oral drug for type 2 diabetes, is attracting attention as a new supportive therapy against a variety of diseases, such as cancer and infectious diseases. The novel mechanisms for metformin actions include modulation of the effector functions of macrophages and other host immune cells. In this study, we have examined the effects of metformin on L. pneumophila infection in vitro and in vivo. Metformin treatment suppressed growth of L...
January 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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