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https://www.readbyqxmd.com/read/28403148/human-neutrophil-peptide-1-promotes-alcohol-induced-hepatic-fibrosis-and-hepatocyte-apoptosis
#1
Rie Ibusuki, Hirofumi Uto, Kohei Oda, Akihiko Ohshige, Kazuaki Tabu, Seiichi Mawatari, Kotaro Kumagai, Shuji Kanmura, Tsutomu Tamai, Akihiro Moriuchi, Hirohito Tsubouchi, Akio Ido
BACKGROUND AND AIMS: Neutrophil infiltration of the liver is a typical feature of alcoholic liver injury. Human neutrophil peptide (HNP)-1 is an antimicrobial peptide secreted by neutrophils. The aim of this study was to determine if HNP-1 affects ethanol-induced liver injury and to examine the mechanism of liver injury induced by HNP-1. METHODS: Transgenic (TG) mice expressing HNP-1 under the control of a β-actin-based promoter were established. Ethanol was orally administered to HNP-1 TG or wild-type C57BL/6N (WT) mice...
2017: PloS One
https://www.readbyqxmd.com/read/28377639/nash-novel-therapeutic-strategies-targeting-ask1-in-nash
#2
Susanne Schuster, Ariel E Feldstein
No abstract text is available yet for this article.
April 5, 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28360100/trans-fatty-acids-promote-proinflammatory-signaling-and-cell-death-by-stimulating-the-apoptosis-signal-regulating-kinase-1-ask1-p38-pathway
#3
Yusuke Hirata, Miki Takahashi, Yuki Kudoh, Kuniyuki Kano, Hiroki Kawana, Kumiko Makide, Yasuharu Shinoda, Yasushi Yabuki, Kohji Fukunaga, Junken Aoki, Takuya Noguchi, Atsushi Matsuzawa
Food-borne trans-fatty acids (TFAs) are mainly produced as byproducts during food manufacture. Recent epidemiological studies have revealed that TFA consumption is a major risk factor for various disorders, including atherosclerosis. However, the underlying mechanisms in this disease etiology are largely unknown. Here, we have shown that TFAs potentiate activation of apoptosis signal-regulating kinase 1 (ASK1) induced by extracellular ATP, a damage-associated molecular pattern (DAMP) leaked from injured cells...
March 29, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28349059/psoralen-inhibited-apoptosis-of-osteoporotic-osteoblasts-by-modulating-ire1-ask1-jnk-pathway
#4
Shuqing Chen, Yongqian Wang, Yubin Yang, Ting Xiang, Jiahui Liu, Houming Zhou, Xinlin Wu
Osteoporosis is a common disease causing fracture in older populations. Abnormal apoptosis of osteoblasts contributes to the genesis of osteoporosis. Inhibiting apoptosis of osteoblasts provides a promising strategy to prevent osteoporosis. The proliferation of osteoblasts isolated from osteoporotic patients or healthy subjects was determined by MTT assay. Apoptosis was determined by Annexin V/PI assay. Protein expression was measured by western blot. The proliferation of osteoblasts isolated from osteoporotic patients was inhibited and the apoptosis level of these cells was higher than the osteoblasts from healthy subjects...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28337323/structure-based-design-of-ask1-inhibitors-as-potential-agents-for-heart-failure
#5
Marion Lanier, Jason Pickens, Simone V Bigi, Erica L Bradshaw-Pierce, Alison Chambers, Zacharia S Cheruvallath, Derek Cole, Douglas R Dougan, Jacques Ermolieff, Tony Gibson, Petro Halkowycz, Aki Hirokawa, Anthony Ivetac, Joanne Miura, Evan Nunez, Mark Sabat, John Tyhonas, Haixia Wang, Xiaolun Wang, Steve Swann
Apoptosis signal-regulating kinase 1 (ASK1/MAP3K) is a mitogen-activated protein kinase family member shown to contribute to acute ischemia/reperfusion injury. Using structure-based drug design, deconstruction, and reoptimization of a known ASK1 inhibitor, a lead compound was identified. This compound displayed robust MAP3K pathway inhibition and reduction of infarct size in an isolated perfused heart model of cardiac injury.
March 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28335665/calcium-oxalate-crystals-induces-tight-junction-disruption-in-distal-renal-tubular-epithelial-cells-by-activating-ros-akt-p38-mapk-signaling-pathway
#6
Lei Yu, Xiuguo Gan, Xukun Liu, Ruihua An
Tight junction plays important roles in regulating paracellular transports and maintaining cell polarity. Calcium oxalate monohydrate (COM) crystals, the major crystalline composition of kidney stones, have been demonstrated to be able to cause tight junction disruption to accelerate renal cell injury. However, the cellular signaling involved in COM crystal-induced tight junction disruption remains largely to be investigated. In the present study, we proved that COM crystals induced tight junction disruption by activating ROS/Akt/p38 MAPK pathway...
November 2017: Renal Failure
https://www.readbyqxmd.com/read/28301594/daxx-plays-a-novel-role-in-t-cell-survival-but-is-dispensable-in-fas-induced-apoptosis
#7
Jinghe Li, Liangyue Qian, John P Dowling, Christine Curcione, Drishya Kurup, Jianke Zhang
Daxx was originally isolated as a Fas-binding protein. However, the in vivo function of Daxx in Fas-induced apoptosis has remained enigmatic. Fas plays an important role in homeostasis in the immune system. Fas gene mutations lead to autoimmune-lymphoproliferation (lpr) diseases characterized by hyperplasia of secondary lymphoid organs. It is well established that the FADD adaptor binds to Fas, and recruits/activates caspase 8. However, additional proteins including Daxx have also been indicated to associate with Fas...
2017: PloS One
https://www.readbyqxmd.com/read/28291695/structure-based-drug-design-of-novel-ask1-inhibitors-using-an-integrated-lead-optimization-strategy
#8
Tony S Gibson, Benjamin Johnson, Andrea Fanjul, Petro Halkowycz, Douglas R Dougan, Derek Cole, Steven Swann
Structure-based drug design is an iterative process that is an established means to accelerate lead optimization, and is most powerful when integrated with information from different sources. Herein is described the use of such methods in conjunction with deconstruction and re-optimization of a diverse series of ASK1 chemotypes along with high-throughput screening that lead to the identification of a novel series of efficient ASK1 inhibitors displaying robust MAP3K pathway inhibition.
March 2, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28288548/upregulated-glutathione-transferase-omega-1-correlates-with-progression-of-urinary-bladder-carcinoma
#9
Tatjana Djukic, Tatjana Simic, Marija Pljesa-Ercegovac, Marija Matic, Sonja Suvakov, Vesna Coric, Dejan Dragicevic, Ana Savic-Radojevic
OBJECTIVES: Newly discovered glutathione transferase omega 1 (GSTO1-1) plays an important role in the glutathionylation cycle, a significant mechanism of protein function regulation. GSTO1-1 expression pattern has not been studied in transitional cell carcinoma (TCC), as yet. METHODS: A total of 56 TCC tumor and corresponding non-tumor specimens were investigated. Glutathione content and thioltransferase activity were measured spectrophotometrically. Protein-glutathione mixed disulfides were measured fluorimetrically...
March 13, 2017: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/28284893/gstm1-genotype-is-an-independent-prognostic-factor-in-clear-cell-renal-cell-carcinoma
#10
Vesna M Coric, Tatjana P Simic, Tatjana D Pekmezovic, Gordana M Basta-Jovanovic, Ana R Savic-Radojevic, Sanja M Radojevic-Skodric, Marija G Matic, Sonja R Suvakov, Dejan P Dragicevic, Tanja M Radic, Zoran M Dzamic, Marija S Pljesa-Ercegovac
PURPOSE: Owing to dual functionality of cytosolic glutathione S-transferases (GSTs), they might affect both the development and the progression of renal cell carcinoma (RCC). However, the data on the prognostic value of GST polymorphism in patients with RCC are scarce. Hence, we evaluated the effect of GST gene variants on both the risk of RCC development and the postoperative prognosis in patients with clear cell RCC (ccRCC). METHODS: GST genotypes were determined in 305 patients with RCC and 326 matched controls, whereas the overall survival was evaluated in patients with ccRCC only...
March 8, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28254824/stressed-platelets-ask1-for-a-mapk
#11
Robert Flaumenhaft
No abstract text is available yet for this article.
March 2, 2017: Blood
https://www.readbyqxmd.com/read/28243335/the-epstein-barr-virus-encoded-mir-bart22-targets-map3k5-to-promote-host-cell-proliferative-and-invasive-abilities-in-nasopharyngeal-carcinoma
#12
Ruichao Chen, Minfeng Zhang, Qiulian Li, Hanzhen Xiong, Shaoyan Liu, Weiyi Fang, Qianbing Zhang, Zhen Liu, Xuehu Xu, Qingping Jiang
miR-BART22, a new discovered Epstein-Barr virus (EBV) miRNA, is abundant in Nasopharyngeal carcinoma (NPC). It has been reported that miR-BART22 promoted the tumor development by down-modulating EBV LMP2 expression to evade the host immune response. But its cell target genes have still been obscure. We have reported an inverse correlation between the BART-22 and MAP3K5 protein expression in NPC tissues and NPC cell lines. Meanwhile, MAP3K5 protein expression level was significantly decreased in primary NPC tissues compared with nasopharyngitis when MAP3K5 mRNA expression was consistent in two group tissues...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28242696/structural-basis-of-autoregulatory-scaffolding-by-apoptosis-signal-regulating-kinase-1
#13
Johannes F Weijman, Abhishek Kumar, Sam A Jamieson, Chontelle M King, Tom T Caradoc-Davies, Elizabeth C Ledgerwood, James M Murphy, Peter D Mace
Apoptosis signal-regulating kinases (ASK1-3) are apical kinases of the p38 and JNK MAP kinase pathways. They are activated by diverse stress stimuli, including reactive oxygen species, cytokines, and osmotic stress; however, a molecular understanding of how ASK proteins are controlled remains obscure. Here, we report a biochemical analysis of the ASK1 kinase domain in conjunction with its N-terminal thioredoxin-binding domain, along with a central regulatory region that links the two. We show that in solution the central regulatory region mediates a compact arrangement of the kinase and thioredoxin-binding domains and the central regulatory region actively primes MKK6, a key ASK1 substrate, for phosphorylation...
March 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28219095/kaempferol-attenuates-cardiac-hypertrophy-via-regulation-of-ask1-mapk-signaling-pathway-and-oxidative-stress
#14
Hong Feng, Jianlei Cao, Guangyu Zhang, Yanggan Wang
Kaempferol has been demonstrated to provide benefits for the treatment of atherosclerosis, coronary heart disease, hyperlipidemia, and diabetes through its antioxidant and anti-inflammatory properties. However, its role in cardiac hypertrophy remains to be elucidated. The aim of our study was to investigate the effects of kaempferol on cardiac hypertrophy and the underlying mechanism. Mice subjected to aorta banding were treated with or without kaempferol (100 mg/kg/d, p. o.) for 6 weeks. Echocardiography was performed to evaluate cardiac function...
February 20, 2017: Planta Medica
https://www.readbyqxmd.com/read/28218919/targeting-casp8-and-fadd-like-apoptosis-regulator-ameliorates-nonalcoholic-steatohepatitis-in-mice-and-nonhuman-primates
#15
Pi-Xiao Wang, Yan-Xiao Ji, Xiao-Jing Zhang, Ling-Ping Zhao, Zhen-Zhen Yan, Peng Zhang, Li-Jun Shen, Xia Yang, Jing Fang, Song Tian, Xue-Yong Zhu, Jun Gong, Xin Zhang, Qiao-Fang Wei, Yong Wang, Jing Li, Lu Wan, Qingguo Xie, Zhi-Gang She, Zhihua Wang, Zan Huang, Hongliang Li
Nonalcoholic steatohepatitis (NASH) is a progressive disease that is often accompanied by metabolic syndrome and poses a high risk of severe liver damage. However, no effective pharmacological treatment is currently available for NASH. Here we report that CASP8 and FADD-like apoptosis regulator (CFLAR) is a key suppressor of steatohepatitis and its metabolic disorders. We provide mechanistic evidence that CFLAR directly targets the kinase MAP3K5 (also known as ASK1) and interrupts its N-terminus-mediated dimerization, thereby blocking signaling involving ASK1 and the kinase MAPK8 (also known as JNK1)...
April 2017: Nature Medicine
https://www.readbyqxmd.com/read/28210980/molecular-mechanisms-of-ire1%C3%AE-ask1-pathway-reactions-to-unfolded-protein-response-in-drn-neurons-of-post-traumatic-stress-disorder-rats
#16
Fanzhen Kong, Fang Han, Yanhao Xu, Yuxiu Shi
The goal of this study was to further elucidate the molecular mechanisms of post-traumatic stress disorder (PTSD) pathogenesis and to provide experimental evidence for new drug targets for effective PTSD treatment. Expression changes of IRE1α, ASK1, and other downstream molecules of the IRE1α-ASK1 endoplasmic reticulum stress (ERS) signaling pathway were investigated. JNK, P38, CHOP, Bcl-2, and Bax were analyzed at both protein and mRNA levels of dorsal raphe nucleus (DRN) neurons of PTSD rats. The rat PTSD model was established via the single-prolonged stress (SPS) method...
April 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28195154/zinc-finger-protein-zpr9-functions-as-an-activator-of-ampk-related-serine-threonine-kinase-mpk38-melk-involved-in-ask1-tgf-%C3%AE-p53-signaling-pathways
#17
Hyun-A Seong, Ravi Manoharan, Hyunjung Ha
Murine protein serine-threonine kinase 38 (MPK38), an AMP-activated protein kinase (AMPK)-related kinase, has been implicated in the induction of apoptosis signal-regulating kinase 1 (ASK1)-, transforming growth factor-β (TGF-β)-, and p53-mediated activity involved in metabolic homeostasis. Here, zinc finger protein ZPR9 was found to be an activator of MPK38. The association of MPK38 and ZPR9 was mediated by cysteine residues present in each of these two proteins, Cys(269) and Cys(286) of MPK38 and Cys(305) and Cys(308) of ZPR9...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28119399/an-als-associated-mutant-sod1-rapidly-suppresses-kcnt1-slack-na-activated-k-channels-in-aplysia-neurons
#18
Yalan Zhang, Weiming Ni, Arthur L Horwich, Leonard K Kaczmarek
Mutations that alter levels of Slack (KCNT1) Na(+)-activated K(+) current produce devastating effects on neuronal development and neuronal function. We now find that Slack currents are rapidly suppressed by oligomers of mutant human Cu/Zn superoxide dismutase 1 (SOD1), which are associated with motor neuron toxicity in an inherited form of amyotrophic lateral sclerosis (ALS). We recorded from bag cell neurons of Aplysia californica, a model system to study neuronal excitability. We found that injection of fluorescent wild-type SOD1 (wt SOD1YFP) or monomeric mutant G85R SOD1YFP had no effect on net ionic currents measured under voltage clamp...
February 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28045936/detoxification-of-mitochondrial-oxidants-and-apoptotic-signaling-are-facilitated-by-thioredoxin-2-and-peroxiredoxin-3-during-hyperoxic-injury
#19
Benjamin J Forred, Darwin R Daugaard, Brianna K Titus, Ryan R Wood, Miranda J Floen, Michelle L Booze, Peter F Vitiello
Mitochondria play a fundamental role in the regulation of cell death during accumulation of oxidants. High concentrations of atmospheric oxygen (hyperoxia), used clinically to treat tissue hypoxia in premature newborns, is known to elicit oxidative stress and mitochondrial injury to pulmonary epithelial cells. A consequence of oxidative stress in mitochondria is the accumulation of peroxides which are detoxified by the dedicated mitochondrial thioredoxin system. This system is comprised of the oxidoreductase activities of peroxiredoxin-3 (Prx3), thioredoxin-2 (Trx2), and thioredoxin reductase-2 (TrxR2)...
2017: PloS One
https://www.readbyqxmd.com/read/28043644/differential-expression-of-survival-proteins-during-decreased-intracellular-oxygen-tension-in-brain-endothelial-cells-of-grey-mullets
#20
Padmini Ekambaram, Meenakshi Narayanan, Parimala Parasuraman
The brain requires constant oxygen supply to perform its biological functions essential for survival. Because of low oxygen capacity and poor oxygen diffusibility of water, many fish species have evolved various adaptive mechanisms to cope with depleted oxygen. Endothelial cells (EC) are the primary components responsible for controlled environment of brain. Brain homeostasis largely depends on integrity of the EC. To elucidate their adaptive strategy, EC were isolated from the fish brain of Kovalam-control site and Ennore estuary-test/field hypoxic site and were subjected to low oxygen tension in laboratory...
December 30, 2016: Marine Pollution Bulletin
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