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https://www.readbyqxmd.com/read/29154282/role-of-ask1-p38-cascade-in-a-mouse-model-of-alzheimer-s-disease-and-brain-aging
#1
Yu Hasegawa, Kensuke Toyama, Ken Uekawa, Hidenori Ichijo, Shokei Kim-Mitsuyama
To examine the role of ASK1 in Alzheimer's disease (AD), we generated 5XFAD mice deficient in ASK1 and investigated the characteristics of old 5XFAD and wild-type mice with ASK1 deficiency. ASK1 deficiency improved cognitive function in 24-month-old 5XFAD mice, which was associated with the reduction of phosphorylated p38. Thus, ASK1/p38 cascade seems to play some role in the pathogenesis of AD in mice. In 24-month-old wild-type mice, ASK1 deficiency increased cerebral vasoreactivity to acetazolamide and significantly reduced brain soluble Aβ, which were also associated with the reduction of phosphorylated p38...
November 14, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29147906/regulation-of-signal-transduction-by-dj-1
#2
Stephanie E Oh, M Maral Mouradian
The ability of DJ-1 to modulate signal transduction has significant effects on how the cell regulates normal processes such as growth, senescence, apoptosis, and autophagy to adapt to changing environmental stimuli and stresses. Perturbations of DJ-1 levels or function can disrupt the equilibrium of homeostatic signaling networks and set off cascades that play a role in the pathogenesis of conditions such as cancer and Parkinson's disease.DJ-1 plays a major role in various pathways. It mediates cell survival and proliferation by activating the extracellular signal-regulated kinase (ERK1/2) pathway and the phosphatidylinositol-3-kinase (PI3K)/Akt pathway...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29147904/the-multifaceted-roles-of-dj-1-as-an-antioxidant
#3
Prahlad V Raninga, Giovanna Di Trapani, Kathryn F Tonissen
The DJ-1 protein was originally linked with Parkinson's disease and is now known to have antioxidant functions. The protein has three redox-sensitive cysteine residues, which are involved in its dimerisation and functional properties. A mildly oxidised form of DJ-1 is the most active form and protects cells from oxidative stress conditions. DJ-1 functions as an antioxidant through a variety of mechanisms, including a weak direct antioxidant activity by scavenging reactive oxygen species. DJ-1 also regulates a number of signalling pathways, including the inhibition of apoptosis signal-regulating kinase 1 (ASK1)-induced apoptosis under oxidative stress conditions...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29133922/essential-role-of-mitochondrial-stat3-in-p38-mapk-mediated-apoptosis-under-oxidative-stress
#4
Xinlai Cheng, Christiane Peuckert, Stefan Wölfl
Stat3 is an oncogene, frequently associated with malignant transformation. A body of evidence implicates that phospho-Stat3(Y705) contributes to its nucleic translocation, while phospho-Stat3(S727) leads to the accumulation in mitochondria. Both are of importance for tumor cell proliferation. In comparison to well-characterized signaling pathways interplaying with Stat3(Y705), little is known about Stat3(S727). In this work, we studied the influence of Stat3 deficiency on the viability of cells exposed to H2O2 or hypoxia using siRNA and CRISPR/Cas9 genome-editing...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29122554/physiological-roles-of-ask-family-members-in-innate-immunity-and-their-involvement-in-pathogenesis-of-immune-diseases
#5
REVIEW
Atsushi Matsuzawa
Cells are always exposed to various types of stress, including physical, chemical, and biological stresses, and are required to sense immediately and respond appropriately to these stresses. The apoptosis signal-regulating kinase (ASK) family members are stress-responsive kinases, which are activated by not only physicochemical stresses, such as oxidative stress, osmotic pressure, calcium overload, and anti-cancer drugs, but also biological stresses, such as inflammatory cytokines and pathogen infection. Recently, we found that ASK1, a member of ASK family, is activated by bacterial components, such as lipopolysaccharide, in a reactive oxygen species (ROS)-dependent manner, demonstrating that ASK1 is required for the innate immune response and plays a critical role in the regulation of innate immune signaling...
October 19, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29118905/intramyocardial-injection-of-thioredoxin-2-expressing-lentivirus-alleviates-myocardial-ischemia-reperfusion-injury-in-rats
#6
Yanyan Li, Yin Xiang, Song Zhang, Yan Wang, Jie Yang, Wei Liu, Fengtai Xue
The aim of this study is to explore the role of thioredoxin-2 (Trx2) in autophagy and apoptosis during myocardial ischemia-reperfusion (I/R) injury in vivo. In the study, adult male Sprague-Dawley rats were assigned to four groups at random and pretreated with normal saline (sham operation and I/R groups) and either a control lentivirus (Lv-GFP-N) or one expressing Trx2 (Lv-GFP-Trx2). Sevendays after pretreatment, rat MIRI models were produced via occlusion of the left anterior descending coronary artery for 30 min followed by reperfusion for 6 h...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29107962/apoptosis-signal-regulating-kinase-1-inhibition-attenuates-cardiac-hypertrophy-and-cardiorenal-fibrosis-induced-by-uremic-toxins-implications-for-cardiorenal-syndrome
#7
Feby Savira, Longxing Cao, Ian Wang, Wendi Yang, Kevin Huang, Yue Hua, Beat M Jucker, Robert N Willette, Li Huang, Henry Krum, Zhiliang Li, Qiang Fu, Bing Hui Wang
Intracellular accumulation of protein-bound uremic toxins in the setting of cardiorenal syndrome leads to adverse effects on cardiorenal cellular functions, where cardiac hypertrophy and cardiorenal fibrosis are the hallmarks. In this study, we sought to determine if Apoptosis Signal-Regulated Kinase 1 (ASK1), an upstream regulator of cellular stress response, mediates cardiac hypertrophy and cardiorenal fibrosis induced by indoxyl sulfate (IS) and p-cresol sulfate (PCS) in vitro, and whether ASK1 inhibition is beneficial to ameliorate these cellular effects...
2017: PloS One
https://www.readbyqxmd.com/read/29107687/mir-150-deficiency-ameliorated-hepatosteatosis-and-insulin-resistance-in-nonalcoholic-fatty-liver-disease-via-targeting-casp8-and-fadd-like-apoptosis-regulator
#8
Baozhong Zhuge, Guohong Li
The prevalence of Non-alcoholic fatty liver diseases (NAFLD) increased rapidly in the world. However, the pathogenesis of is still unclear. Hepatic steatosis and insulin resistance are considered to be central to the pathophysiology of NAFLD. MicroRNAs are short non-coding RNAs and has been reported to be involved in pathogenesis of NAFLD and related metabolic diseases. Here, we investigated the mechanisms by which miR-150 regulate hepatic steatosis and insulin resistance in high fat diet (HFD) induced NAFLD model...
October 28, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29107568/ask-family-in-cardiovascular-biology-and-medicine
#9
REVIEW
Tingting Liu, Huanjiao Jenny Zhou, Wang Min
Cardiovascular disease is a major cause of death worldwide. Mitogen-activated protein kinase (MAPK) signal cascades signaling pathways play crucial roles in cardiovascular pathophysiology. Apoptosis signal-regulating kinase (ASK) family members ASK1, ASK2 and ASK3 are the key molecules in MAPK signal cascades and are activated by various stresses. ASK1 is the most extensively studied MAPKKK and is involved in regulation of the cellular functions such as cell survival, proliferation, inflammation and apoptosis...
October 24, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29102394/regulation-of-ask1-signaling-by-scaffold-and-adaptor-proteins
#10
REVIEW
Lauren Rusnak, Haian Fu
The mitogen-activated protein kinase (MAPK) signaling pathway is a three-tiered kinase cascade where mitogen-activated protein kinase kinase kinases (MAP3Ks) lead to the activation of mitogen-activated protein kinase kinases (MAP2K), and ultimately MAPK proteins. MAPK signaling can promote a diverse set of biological outcomes, ranging from cell death to proliferation. There are multiple mechanisms which govern MAPK output, such as the duration and strength of the signal, cellular localization to upstream and downstream binding partners, pathway crosstalk and the binding to scaffold and adaptor molecules...
October 16, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29066278/structural-aspects-of-protein-kinase-ask1-regulation
#11
REVIEW
Tomas Obsil, Veronika Obsilova
Apoptosis signal-regulating kinase 1 (ASK1, also known as MAP3K5), a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family, activates the p38 mitogen-activated protein kinase and the c-Jun N-terminal kinase (JNK) signaling cascades in response to various stressors. ASK1 activity is tightly regulated through phosphorylation and interaction with various binding partners. However, the mechanistic details underlying the ASK1 regulation are still not fully understood. This review focuses on recent advances in structural studies of protein kinase ASK1 and on the insights they provide into its mechanism of regulation...
October 16, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29066277/therapeutic-application-of-apoptosis-signal-regulating-kinase-1-inhibitors
#12
REVIEW
Takao Fujisawa
Apoptosis signal-regulating kinase 1 (ASK1) is a member of the stress-activated mitogen-activated protein kinase kinase kinase (MAP3K) family. ASK1 is an attractive drug target, owing to its essential role in a wide variety of human diseases including neurodegenerative disorders, inflammatory diseases and cancer. Recent studies have suggested that pharmacological manipulations using small molecule ASK1 inhibitors may be beneficial in experimental human disease models. In this review, we highlight the current understanding of ASK1 inhibitors as a potential therapy for human diseases...
October 16, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29045420/inhibition-of-apoptosis-signal-regulating-kinase-1-alters-the-wound-epidermis-and-enhances-auricular-cartilage-regeneration
#13
Qian-Shi Zhang, Deepa S Kurpad, My G Mahoney, Marla J Steinbeck, Theresa A Freeman
Why regeneration does not occur in mammals remains elusive. In lower vertebrates, epimorphic regeneration of the limb is directed by the wound epidermis, which controls blastema formation to promote regrowth of the appendage. Herein, we report that knockout (KO) or inhibition of Apoptosis Signal-regulated Kinase-1 (ASK1), also known as mitogen-activated protein kinase kinase kinase 5 (MAP3K5), after full thickness ear punch in mice prolongs keratinocyte activation within the wound epidermis and promotes regeneration of auricular cartilage...
2017: PloS One
https://www.readbyqxmd.com/read/29044621/protective-roles-of-hepatic-gamma-aminobutyric-acid-signaling-in-acute-ethanol-exposure-induced-liver-injury
#14
Shuanglian Wang, Shaofeng Sui, Zhiyan Liu, Cheng Peng, Jia Liu, Dan Luo, Xinhuan Fan, Chuanyong Liu, Wei-Yang Lu
Alcoholic liver disease (ALD) is a consequence of heavy and prolonged alcohol consumptions. We previously demonstrated a hepatic gamma-aminobutyric acid (GABA) signaling system that protects the liver from toxic injury. The present study was designed to investigate the role of the hepatic GABA signaling system in the process of acute ethanol exposure-induced liver injury. Our results showed that the expression of GABA synthesizing enzyme glutamic acid decarboxylase and type A GABA receptor (GABAA R) subunits was upregulated in ethanol-treated mice compared with saline-treated controls...
October 17, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29038201/kinin-b1-receptor-promotes-neurogenic-hypertension-through-activation-of-centrally-mediated-mechanisms
#15
Srinivas Sriramula, Eric Lazartigues
Hypertension is associated with increased activity of the kallikrein-kinin system. Kinin B1 receptor (B1R) activation leads to vasoconstriction and inflammation. Despite evidence supporting a role for the B1R in blood pressure regulation, the mechanisms by which B1R could alter autonomic function and participate in the pathogenesis of hypertension remain unidentified. We sought to explore whether B1R-mediated inflammation contributes to hypertension and investigate the molecular mechanisms involved. In this study, we tested the hypothesis that activation of B1R in the brain is involved in the pathogenesis of hypertension, using the deoxycorticosterone acetate-salt model of neurogenic hypertension in wild-type and B1R knockout mice...
December 2017: Hypertension
https://www.readbyqxmd.com/read/29018270/nafld-early-promise-for-ask1-inhibition-in-nash
#16
Katrina Ray
No abstract text is available yet for this article.
November 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28977868/thioredoxin-plays-a-key-role-in-retinal-neuropathy-prior-to-endothelial-damage-in-diabetic-mice
#17
Xiang Ren, Chen Li, Junli Liu, Chenghong Zhang, Yuzhen Fu, Nina Wang, Haiying Ma, Heyuan Lu, Hui Kong, Li Kong
Diabetes is a chronic metabolic syndrome that results in changes in carbohydrate, lipid and protein metabolism. With diabetes for a long time, it increases the risk of diabetic retinopathy (DR) and long-term morbidity and mortality. Moreover, emerging evidence suggests that neuron damage occurs earlier than microvascular complications in DR patients, but the underlying mechanism is unclear. We investigated diabetes-induced retinal neuropathy and elucidated key molecular events to identify new therapeutic targets for the clinical treatment and prevention of DR...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28973931/systems-level-identification-of-pka-dependent-signaling-in-epithelial-cells
#18
Kiyoshi Isobe, Hyun Jun Jung, Chin-Rang Yang, J'Neka Claxton, Pablo Sandoval, Maurice B Burg, Viswanathan Raghuram, Mark A Knepper
G protein stimulatory α-subunit (Gαs)-coupled heptahelical receptors regulate cell processes largely through activation of protein kinase A (PKA). To identify signaling processes downstream of PKA, we deleted both PKA catalytic subunits using CRISPR-Cas9, followed by a "multiomic" analysis in mouse kidney epithelial cells expressing the Gαs-coupled V2 vasopressin receptor. RNA-seq (sequencing)-based transcriptomics and SILAC (stable isotope labeling of amino acids in cell culture)-based quantitative proteomics revealed a complete loss of expression of the water-channel gene Aqp2 in PKA knockout cells...
October 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28973341/edaravone-prevents-retinal-degeneration-in-adult-mice-following-optic-nerve-injury
#19
Goichi Akiyama, Yuriko Azuchi, Xiaoli Guo, Takahiko Noro, Atsuko Kimura, Chikako Harada, Kazuhiko Namekata, Takayuki Harada
Purpose: To assess the therapeutic potential of edaravone, a free radical scavenger that is used for the treatment of acute brain infarction and amyotrophic lateral sclerosis, in a mouse model of optic nerve injury (ONI). Methods: Two microliters of edaravone (7.2 mM) or vehicle were injected intraocularly 3 minutes after ONI. Optical coherence tomography, retrograde labeling of retinal ganglion cells (RGCs), histopathology, and immunohistochemical analyses of phosphorylated apoptosis signal-regulating kinase-1 (ASK1) and p38 mitogen-activated protein kinase (MAPK) in the retina were performed after ONI...
September 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28965952/interleukin-33-attenuates-doxorubicin-induced-cardiomyocyte-apoptosis-through-suppression-of-ask1-jnk-signaling-pathway
#20
Yongwei Yao, Rong Chen, Chunyang Ying, Guohui Zhang, Tao Rui, Aibin Tao
Interleukin-33 (IL-33), a new member of the IL-1 cytokine family, has cardiac protective effect in many circumstances. The aims of present study are to assess whether IL-33 can protect cardiomyocytes from doxorubicin (DOX)-induced apoptosis and the mechanism involved in the protection. Cardiomyocytes derived from either wild-type or c-Jun N-terminal kinase deficient (JNK(-/-)) mice were challenged with DOX (1  μM) with or without IL-33 (10 ng/ml). Myocyte apoptosis was assessed by measuring Caspase 3 activity, fragmented DNA and the TUNEL staining...
November 25, 2017: Biochemical and Biophysical Research Communications
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