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https://www.readbyqxmd.com/read/29769309/etoposide-induced-protein-2-4-functions-as-a-regulator-of-the-calcium-atpase-and-protects-pancreatic-%C3%AE-cell-survival
#1
Lin Yuan, Huiyu Wang, Qi Liu, Zhe Wang, Mingshu Zhang, Yan Zhao, Kuo Liang, Liangyi Chen, Tao Xu, Pingyong Xu
Calcium homeostasis is essential for maintaining the viability and function of pancreatic β cells and plays a key role in preventing the development of diabetes. Decreased levels of ATPase sarco-plasmic/endoplasmic reticulum Ca2+ -transporting 2 (ATP2a2), the main calcium pump in β cells, are often found in individuals with diabetes and in diabetic animal models. However, the regulators of ATP2a2 and the molecular mechanisms responsible for controlling ATP2a2 activity remain unclear. Etoposide-induced protein 2...
May 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29691479/alternative-polyadenylation-drives-genome-to-phenome-information-detours-in-the-ampk%C3%AE-1-and-ampk%C3%AE-2-knockout-mice
#2
Shuwen Zhang, Yangzi Zhang, Xiang Zhou, Xing Fu, Jennifer J Michal, Guoli Ji, Min Du, Jon F Davis, Zhihua Jiang
Currently available mouse knockout (KO) lines remain largely uncharacterized for genome-to-phenome (G2P) information flows. Here we test our hypothesis that altered myogenesis seen in AMPKα1- and AMPKα2-KO mice is caused by use of alternative polyadenylation sites (APSs). AMPKα1 and AMPKα2 are two α subunits of adenosine monophosphate-activated protein kinase (AMPK), which serves as a cellular sensor in regulation of many biological events. A total of 56,483 APSs were derived from gastrocnemius muscles...
April 24, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29614883/bergamottin-inhibits-adipogenesis-in-3t3-l1-cells-and-weight-regulation-in-diet-induced-obese-mice
#3
Jeong-Hyeon Ko, Dongwoo Nam, Jae-Young Um, Sang Hoon Jung, Kwang Seok Ahn
Obesity is a serious and increasing health problem worldwide, and the inhibition of adipogenesis is considered to be a potential therapeutic target for it. Bergamottin (BGM), a component of grapefruit juice, has been reported to regulate lipolysis. However, the physiological role of BGM in obesity has not been evaluated so far. In the present study, we investigated the effects of BGM on obesity in 3T3-L1 cells and in mice fed a high-fat diet (HFD). BGM inhibited adipogenic differentiation of 3T3-L1 cells along with a significant decrease in the lipid content by downregulating the expression of two critical adipogenic factors, CCAAT enhancer-binding protein-alpha (C/EBP[Formula: see text]) and peroxisome proliferator activated receptor-gamma (PPAR[Formula: see text])...
April 4, 2018: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29588219/exercise-induced-reductions-in-mitochondrial-adp-sensitivity-contribute-to-the-induction-of-gene-expression-and-mitochondrial-biogenesis-through-enhanced-mitochondrial-h-2-o-2-emission
#4
Paula M Miotto, Graham P Holloway
Acute exercise rapidly induces mitochondrial gene expression, however, the intracellular events regulating this process remain incompletely understood. The purpose of this study was to determine whether reductions in mitochondrial ADP sensitivity during exercise have a biological role in regulating mitochondrial-derived reactive oxygen species (ROS) production and the induction of mitochondrial biogenesis. Mitochondrial creatine kinase wildtype (WT) and knockout (KO) mice have divergent responses in ADP sensitivity during exercise, and we therefore used these mice to determine the relationship between mitochondrial ADP sensitivity, ROS production, and mitochondrial adaptations to exercise...
March 24, 2018: Mitochondrion
https://www.readbyqxmd.com/read/29515462/amp-activated-protein-kinase-ampk-regulates-energy-metabolism-through-modulating-thermogenesis-in-adipose-tissue
#5
Lingyan Wu, Lina Zhang, Bohan Li, Haowen Jiang, Yanan Duan, Zhifu Xie, Lin Shuai, Jia Li, Jingya Li
Obesity occurs when excess energy accumulates in white adipose tissue (WAT), whereas brown adipose tissue (BAT), which is specialized in dissipating energy through thermogenesis, potently counteracts obesity. White adipocytes can be converted to thermogenic "brown-like" cells (beige cells; WAT browning) under various stimuli, such as cold exposure. AMP-activated protein kinase (AMPK) is a crucial energy sensor that regulates energy metabolism in multiple tissues. However, the role of AMPK in adipose tissue function, especially in the WAT browning process, is not fully understood...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29480499/evaluating-the-role-of-host-ampk-in-leishmania-burden
#6
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/29479319/high-fat-diet-attenuates-the-anticontractile-activity-of-aortic-pvat-via-a-mechanism-involving-ampk-and-reduced-adiponectin-secretion
#7
Tarek A M Almabrouk, Anna D White, Azizah B Ugusman, Dominik S Skiba, Omar J Katwan, Husam Alganga, Tomasz J Guzik, Rhian M Touyz, Ian P Salt, Simon Kennedy
Background and aim: Perivascular adipose tissue (PVAT) positively regulates vascular function through production of factors such as adiponectin but this effect is attenuated in obesity. The enzyme AMP-activated protein kinase (AMPK) is present in PVAT and is implicated in mediating the vascular effects of adiponectin. In this study, we investigated the effect of an obesogenic high fat diet (HFD) on aortic PVAT and whether any changes involved AMPK. Methods: Wild type Sv129 (WT) and AMPKα1 knockout (KO) mice aged 8 weeks were fed normal diet (ND) or HFD (42% kcal fat) for 12 weeks...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29470982/rip3-deficiency-protects-against-traumatic-brain-injury-tbi-through-suppressing-oxidative-stress-inflammation-and-apoptosis-dependent-on-ampk-pathway
#8
Zai-Ming Liu, Qian-Xue Chen, Zhi-Biao Chen, Dao-Feng Tian, Ming-Chang Li, Jun-Min Wang, Long Wang, Bao-Hui Liu, Shen-Qi Zhang, Fei Li, Hui Ye, Long Zhou
Traumatic brain injury (TBI) is a leading cause of disability and mortality in young adults worldwide. The pathophysiology is not fully understood. Programmed necrosis (necroptosis) is a newly identified mechanism of cell death combining features of both apoptosis and necrosis. Receptor-interacting protein 3 (RIP3) plays an important role in programmed necrosis. However, the effect of RIP3-related pathway in TBI is little to be known. We attempted to explore the significance of RIP3 in regulating TBI in vivo...
May 5, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29467198/endothelial-tfeb-transcription-factor-eb-positively-regulates-postischemic-angiogenesis
#9
Yanbo Fan, Haocheng Lu, Wenying Liang, Minerva T Garcia-Barrio, Yanhong Guo, Ji Zhang, Tianqing Zhu, Yibai Hao, Jifeng Zhang, Y Eugene Chen
RATIONALE: Postischemic angiogenesis is critical to limit the ischemic tissue damage and improve the blood flow recovery. The regulation and the underlying molecular mechanisms of postischemic angiogenesis are not fully unraveled. TFEB (transcription factor EB) is emerging as a master gene for autophagy and lysosome biogenesis. However, the role of TFEB in vascular disease is less understood. OBJECTIVE: We aimed to determine the role of endothelial TFEB in postischemic angiogenesis and its underlying molecular mechanism...
March 30, 2018: Circulation Research
https://www.readbyqxmd.com/read/29463997/targeting-aldh2-for-therapeutic-interventions-in-chronic-pain-related-myocardial-ischemic-susceptibility
#10
Chen Li, Wanqing Sun, Chunhu Gu, Zheng Yang, Nanhu Quan, Jingrun Yang, Zhaoling Shi, Lu Yu, Heng Ma
Clinical observations have demonstrated a link between chronic pain and increased ischemic heart disease mortality, but the mechanisms remain elusive. Reactive aldehydes have recently been confirmed as a new player in pain pathologies, while our previous study demonstrated that reactive aldehydes (4-HNE) induced carbonyl stress contributing to myocardial ischemic intolerance. The aim of this study was to explore whether chronic pain increases susceptibility to myocardial ischemia/reperfusion (MI/R) injury and to investigate the underlying mechanisms focusing on toxic aldehyde and carbonyl stress...
2018: Theranostics
https://www.readbyqxmd.com/read/29459374/rescue-of-learning-and-memory-deficits-in-the-human-nonsyndromic-intellectual-disability-cereblon-knock-out-mouse-model-by-targeting-the-amp-activated-protein-kinase-mtorc1-translational-pathway
#11
Charlotte C Bavley, Richard C Rice, Delaney K Fischer, Amanda K Fakira, Maureen Byrne, Maria Kosovsky, Bryant K Rizzo, Dolores Del Prete, Armin Alaedini, Jose A Morón, Joseph J Higgins, Luciano D'Adamio, Anjali M Rajadhyaksha
A homozygous nonsense mutation in the cereblon ( CRBN ) gene results in autosomal recessive, nonsyndromic intellectual disability that is devoid of other phenotypic features, suggesting a critical role of CRBN in mediating learning and memory. In this study, we demonstrate that adult male Crbn knock-out ( Crbn KO ) mice exhibit deficits in hippocampal-dependent learning and memory tasks that are recapitulated by focal knock-out of Crbn in the adult dorsal hippocampus, with no changes in social or repetitive behavior...
March 14, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29453986/sterol-o-acyltransferase-1-deficiency-improves-defective-insulin-signaling-in-the-brains-of-mice-fed-a-high-fat-diet
#12
Ning Xu, Hao Meng, Tian-Yi Liu, Ying-Li Feng, Yuan Qi, Dong-Huan Zhang, Hong-Lei Wang
Insulin resistance induced by a high-fat diet (HFD) is related to metabolic diseases, and sterol O-acyltransferase 1 (SOAT1) is a key enzyme for the biosynthesis of cholesteryl ester. In the present study, wild-type (WT) mice and SOAT1-knockout (KO) mice with a C57BL6 background fed a HFD were used to explore the role of SOAT1 in the hypothalamus. The results show that the WT mice exhibited a significant increase in body weight as well as hepatic histologic changes; they also had a lower glucose and insulin tolerance than the WT mice fed a normal diet...
May 5, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29452207/glycogen-synthase-kinase-3%C3%AE-promotes-liver-innate-immune-activation-by-restraining-amp-activated-protein-kinase-activation
#13
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/29452206/snx10-mediates-alcohol-induced-liver-injury-and-steatosis-by-regulating-the-activation-of-chaperone-mediated-autophagy
#14
Yan You, Wan-Zhen Li, Sulin Zhang, Bin Hu, Yue-Xuan Li, Hai-Dong Li, Huan-Huan Tang, Qian-Wen Li, Yun-Yun Guan, Li-Xin Liu, Wei-Lian Bao, Xiaoyan Shen
BACKGROUND & AIMS: Alcoholic liver disease (ALD) is a major cause of morbidity and mortality worldwide. However, the cellular defense mechanisms underlying ALD are not well understood. Recent studies highlighted the involvement of chaperone-mediated autophagy (CMA) in regulating hepatic lipid metabolism. Sorting nexin (SNX)-10 has a regulatory function in endolysosomal trafficking and stabilisation. Here, we investigated the roles of SNX10 in CMA activation and in the pathogenesis of alcohol-induced liver injury and steatosis...
February 13, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29445083/fibroblast-growth-factor-21-prevents-diabetic-cardiomyopathy-via-ampk-mediated-antioxidation-and-lipid-lowering-effects-in-the-heart
#15
Hong Yang, Anyun Feng, Sundong Lin, Lechu Yu, Xiufei Lin, Xiaoqing Yan, Xuemian Lu, Chi Zhang
Our previous studies showed that both exogenous and endogenous FGF21 inhibited cardiac apoptosis at the early stage of type 1 diabetes. Whether FGF21 induces preventive effect on type 2 diabetes-induced cardiomyopathy was investigated in the present study. High-fat-diet/streptozotocin-induced type 2 diabetes was established in both wild-type (WT) and FGF21-knockout (FGF21-KO) mice followed by treating with FGF21 for 4 months. Diabetic cardiomyopathy (DCM) was diagnosed by significant cardiac dysfunction, remodeling, and cardiac lipid accumulation associated with increased apoptosis, inflammation, and oxidative stress, which was aggravated in FGF21-KO mice...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29409011/cardiomyocyte-specific-deletion-of-sirt1-gene-sensitizes-myocardium-to-ischemia-and-reperfusion-injury
#16
Lin Wang, Nanhu Quan, Wanqing Sun, Xu Chen, Courtney Cates, Thomas Rousselle, Xinchun Zhou, Xuezhong Zhao, Ji Li
Aim: A longevity gene, Sirtuin 1 (SIRT1) and energy sensor AMP-activated protein kinase (AMPK) have common activators such as caloric restriction, oxidative stress and exercise. The objective of this study is to characterize the role of cardiomyocyte SIRT1 in age-related impaired ischemic AMPK activation and increased susceptibility to ischemic insults. Methods and Results: Mice were subjected to ligation of left anterior descending coronary artery for in vivo ischemic models...
February 2, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29408195/hydrogen-sulfide-regulates-cardiac-mitochondrial-biogenesis-via-the-activation-of-ampk
#17
Yuuki Shimizu, Rohini Polavarapu, Kattri-Liis Eskla, Chad K Nicholson, Christopher A Koczor, Rui Wang, William Lewis, Sruti Shiva, David J Lefer, John W Calvert
BACKGROUND: Hydrogen sulfide (H2 S) is an important regulator of mitochondrial bioenergetics, but its role in regulating mitochondrial biogenesis is not well understood. Using both genetic and pharmacological approaches, we sought to determine if H2 S levels directly influenced cardiac mitochondrial content. RESULTS: Mice deficient in the H2 S-producing enzyme, cystathionine γ-lyase (CSE KO) displayed diminished cardiac mitochondrial content when compared to wild-type hearts...
March 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29389248/the-role-of-gp130-in-basal-and-exercise-trained-skeletal-muscle-mitochondrial-quality-control
#18
Dennis K Fix, Justin P Hardee, Song Gao, Brandon N VanderVeen, Kandy T Velazquez, James A Carson
The IL-6 cytokine family activates intracellular signaling pathways through glycoprotein 130 (gp130), and this signaling has established regulatory roles in muscle glucose metabolism and proteostasis. Although the IL-6 family has been implicated as myokines regulating the muscle's metabolic response to exercise, gp130's role in mitochondrial quality control involving fission, fusion, mitophagy and biogenesis is not well understood. Therefore, we examined gp130's role in basal and exercise-trained muscle mitochondrial quality control...
February 1, 2018: Journal of Applied Physiology
https://www.readbyqxmd.com/read/29353038/cereblon-crbn-deletion-reverses-streptozotocin-induced-diabetic-osteoporosis-in-mice
#19
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/29343420/ampk-re-activation-suppresses-hepatic-steatosis-but-its-downregulation-does-not-promote-fatty-liver-development
#20
Nadia Boudaba, Allison Marion, Camille Huet, Rémi Pierre, Benoit Viollet, Marc Foretz
Nonalcoholic fatty liver disease is a highly prevalent component of disorders associated with disrupted energy homeostasis. Although dysregulation of the energy sensor AMP-activated protein kinase (AMPK) is viewed as a pathogenic factor in the development of fatty liver its role has not been directly demonstrated. Unexpectedly, we show here that liver-specific AMPK KO mice display normal hepatic lipid homeostasis and are not prone to fatty liver development, indicating that the decreases in AMPK activity associated with hepatic steatosis may be a consequence, rather than a cause, of changes in hepatic metabolism...
January 9, 2018: EBioMedicine
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