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https://www.readbyqxmd.com/read/27905296/a-pathogenic-role-for-the-integrin-cd103-in-experimental-allergic-airways-disease
#1
Vanessa S Fear, Siew Ping Lai, Graeme R Zosky, Kara L Perks, Shelley Gorman, Fabian Blank, Christophe von Garnier, Philip A Stumbles, Deborah H Strickland
The integrin CD103 is the αE chain of integrin αEβ7 that is important in the maintenance of intraepithelial lymphocytes and recruitment of T cells and dendritic cells (DC) to mucosal surfaces. The role of CD103 in intestinal immune homeostasis has been well described, however, its role in allergic airway inflammation is less well understood. In this study, we used an ovalbumin (OVA)-induced, CD103-knockout (KO) BALB/c mouse model of experimental allergic airways disease (EAAD) to investigate the role of CD103 in disease expression, CD4(+) T-cell activation and DC activation and function in airways and lymph nodes...
November 2016: Physiological Reports
https://www.readbyqxmd.com/read/27904477/axon-injury-induced-endoplasmic-reticulum-stress-and-neurodegeneration
#2
REVIEW
Yang Hu
Injury to central nervous system axons is a common early characteristic of neurodegenerative diseases. Depending on its location and the type of neuron, axon injury often leads to axon degeneration, retrograde neuronal cell death and progressive permanent loss of vital neuronal functions. Although these sequential events are clearly connected, ample evidence indicates that neuronal soma and axon degenerations are active autonomous processes with distinct molecular mechanisms. By exploiting the anatomical and technical advantages of the retinal ganglion cell (RGC)/optic nerve (ON) system, we demonstrated that inhibition of the PERK-eIF2α-CHOP pathway and activation of the X-box binding protein 1 pathway synergistically protect RGC soma and axon, and preserve visual function, in both acute ON traumatic injury and chronic glaucomatous neuropathy...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27899042/hepatic-rhythmicity-of-endoplasmic-reticulum-stress-is-disrupted-in-perinatal-and-adult-mice-models-of-high-fat-diet-induced-obesity
#3
Junpei Soeda, Paul Cordero, Jiawei Li, Angelina Mouralidarane, Esra Asilmaz, Shuvra Ray, Vi Nguyen, Rebeca Carter, Marco Novelli, Manlio Vinciguerra, Lucilla Poston, Paul D Taylor, Jude A Oben
We investigated the regulation of hepatic ER stress in healthy liver and adult or perinatally programmed diet-induced non-alcoholic fatty liver disease (NAFLD). Female mice were fed either obesogenic or control diet before mating, during pregnancy and lactation. Post-weaning, offspring from each maternal group were divided into either obesogenic or control diet. At six months, offspring were sacrificed at 4-h intervals over 24 h. Offspring fed obesogenic diets developed NAFLD phenotype, and the combination of maternal and offspring obesogenic diets exacerbated this phenotype...
November 29, 2016: International Journal of Food Sciences and Nutrition
https://www.readbyqxmd.com/read/27894913/the-regulation-of-cellular-apoptosis-by-the-ros-triggered-perk-eif2%C3%AE-chop-pathway-plays-a-vital-role-in-bisphenol-a-induced-male-reproductive-toxicity
#4
Li Yin, Yanlin Dai, Zhihong Cui, Xiao Jiang, Wenbin Liu, Fei Han, Ao Lin, Jia Cao, Jinyi Liu
Bisphenol A (2,2-bis(4-hydroxyphenyl)propane, BPA) is ubiquitous in the environment, wildlife, and humans. Evidence from past studies suggests that BPA is associated with decreased semen quality. However, the molecular basis for the adverse effect of BPA on male reproductive toxicity remains unclear. We evaluated the effects of BPA on mouse spermatocytes GC-2 cells and adult mice, and we explored the potential mechanism of its action. The results showed that BPA inhibited cell proliferation and increased the apoptosis rate...
November 25, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27894091/preclinical-study-of-cinobufagin-as-a-promising-anti-colorectal-cancer-agent
#5
Xing-Sheng Lu, Yin-Biao Qiao, Ya Li, Bo Yang, Min-Bin Chen, Chun-Gen Xing
Here, we assessed the anti-colorectal cancer (CRC) cell activity of cinobufagin (CBG). We found that CBG exerted potent cytotoxic and anti-proliferative activity against CRC lines (HCT-116 and HT-29) and primary human CRC cells. Meanwhile, it activated apoptosis, and disrupted cell-cycle progression in the cells. At the signaling level, CBG treatment in CRC cells provoked endoplasmic reticulum stress (ER stress), the latter was evidenced by caspase-12 activation, CHOP expression, as well as PERK and IRE1 phosphorylations...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27888615/unconjugated-secondary-bile-acids-activate-the-unfolded-protein-response-and-induce-golgi-fragmentation-via-a-src-kinase-dependant-mechanism
#6
Ruchika Sharma, Francis Quilty, John F Gilmer, Aideen Long, Anne-Marie Byrne
Bile acids are components of gastro-duodenal refluxate and regarded as causative agents in oesophageal disease but the precise mechanisms are unknown. Here we demonstrate that a specific subset of physiological bile acids affect the protein secretory pathway by inducing ER stress, activating the Unfolded Protein Response (UPR) and causing disassembly of the Golgi apparatus in oesophageal cells. Deoxycholic acid (DCA), Chemodeoxycholic acid (CDCA) and Lithocholic acid (LCA) activated the PERK arm of the UPR, via phosphorylation of eIF2α and up-regulation of ATF3, CHOP and BiP/GRP78...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27884737/botulinum-neurotoxin-type-a-alleviates-mechanical-hypersensitivity-associated-with-infraorbital-nerve-constriction-injury-in-rats
#7
Noboru Noma, Kosuke Watanabe, Yuka Sato, Yoshiki Imamura, Yumiko Yamamoto, Reio Ito, Mitsuru Maruno, Kohei Shimizu, Koichi Iwata
We investigated the effect of botulinum neurotoxin type A (BoNT-A) on mechanical allodynia and hyperalgesia associated with infraorbital nerve constriction (ION-CCI) in rats. ION-CCI rats received a subcutaneous BoNT-A injection into the whisker pad area on day 7 postoperatively and underwent pain assessment on days 14 and 21 postoperatively. Rats were assigned to one of four treatment groups (n=5 each): ION-CCI+BoNT-A 20pg (low-dose group), ION-CCI+BoNT-A 200pg (high-dose group), ION-CCI+saline, and Sham. Mechanical allodynia and hyperalgesia were evaluated preoperatively (baseline) and on days 7, 14, and 21 postoperatively...
November 21, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27882565/tanshinone-iia-attenuates-a%C3%AE-25-35-induced-spatial-memory-impairment-via-upregulating-receptors-for-activated-c-kinase1-and-inhibiting-autophagy-in-hippocampus
#8
Jiejun Zhu, Shiping Liao, Liming Zhou, Lihong Wan
OBJECTIVES: Tanshinone IIA (Tan IIA) may exert significant protective effects against the neurotoxicity induced by β-amyloid protein (Aβ). This study was designed to investigate the possible neuroprotective mechanism of Tan IIA on Aβ25-35 -induced spatial memory impairment in mice. METHODS: After 3 weeks of preventive treatment (Tan IIA or oil), all male Kunming mice were subjected to Aβ25-35 (10 μl, intracerebroventricularly (i.c.v.)) to establish the spatial memory impairment model...
November 23, 2016: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/27882154/kai-xin-san-a-traditional-chinese-medicine-formulation-exerts-antidepressive-and-neuroprotective-effects-by-promoting-pcreb-upstream-pathways
#9
Xian-Zhe Dong, Dong-Xiao Wang, Bing-Ying Yu, Ping Liu, Yuan Hu
Kai-Xin-San (KXS) is a traditional Chinese medicine that has been widely used for the treatment of emotion-related disease. However, the underlying mechanism remains largely unknown. The present study aimed to examine whether phospho-cAMP response element-binding protein (pCREB) and upstream components, such as extracellular signal-regulated kinase (ERK), phospho-ERK (pERK), phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt), glycogen synthase kinase 3β (GSK3β) and pGSK3β are associated with the antidepressive effect of KXS...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27881782/consolidation-of-goal-directed-action-depends-on-mapk-erk-signaling-in-rodent-prelimbic-cortex
#10
Genevra Hart, Bernard W Balleine
: The prelimbic prefrontal cortex (PL) has consistently been found to be necessary for the acquisition of goal-directed actions in rodents. Nevertheless, the specific cellular processes underlying this learning remain unknown. We assessed changes in learning-related expression of mitogen-activated protein kinase/extracellular signal-related kinase (MAPK/ERK1/2) phosphorylation (pERK) in layers 2-3 and 5-6 of the anterior and posterior PL and in the population of neurons projecting to posterior dorsomedial striatum (pDMS), also implicated in goal-directed learning...
November 23, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27881664/lipid-disequilibrium-disrupts-er-proteostasis-by-impairing-erad-substrate-glycan-trimming-and-dislocation
#11
Milton To, Clark W H Peterson, Melissa A Roberts, Jessica L Counihan, Tiffany T Wu, Mercedes S Forster, Daniel K Nomura, James A Olzmann
The endoplasmic reticulum (ER) mediates the folding, maturation, and deployment of the secretory proteome. Proteins that fail to achieve their native conformation are retained in the ER and targeted for clearance by ER-associated degradation (ERAD), a sophisticated process that mediates the ubiquitin-dependent delivery of substrates to the 26S proteasome for proteolysis. Recent findings indicate that inhibition of long-chain acyl-CoA synthetases with triacsin C, a fatty acid analog, impairs lipid droplet (LD) biogenesis and ERAD, suggesting a role for LDs in ERAD...
November 23, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27879259/unexpected-role-for-p19ink4d-in-post-transcriptional-regulation-of-gata1-and-modulation-of-human-terminal-erythropoiesis
#12
Xu Han, Jieying Zhang, Yuanliang Peng, Minyuan Peng, Xiao Chen, Huiyong Chen, Jianhui Song, Xiao Hu, Mao Ye, Jianglin Li, Vijay G Sankaran, Christopher D Hillyer, Narla Mohandas, Xiuli An, Jing Liu
Terminal erythroid differentiation is tightly coordinated with cell cycle exit, which is regulated by cyclins, cyclin-dependent kinases and cyclin-dependent kinase inhibitors (CDKI), yet their roles in erythropoiesis remain to be fully defined. We show here that p19(INK4d), a member of CDKI family, is abundantly expressed in erythroblasts and that p19(INK4d) knockdown delayed erythroid differentiation, inhibited cell growth, led to increased apoptosis and generation of abnormally nucleated late stage erythroblasts...
November 22, 2016: Blood
https://www.readbyqxmd.com/read/27877136/novel-role-of-er-stress-and-autophagy-in-microcystin-lr-induced-apoptosis-in-chinese-hamster-ovary-cells
#13
Shenshen Zhang, Chuanrui Liu, Yang Li, Mustapha U Imam, Hui Huang, Haohao Liu, Yongjuan Xin, Huizhen Zhang
Microcystin-LR (MC-LR) is a ubiquitous peptide that exhibits strong reproductive toxicity, although the mechanistic basis for such toxicity remains largely unknown. The present study was conducted to investigate the mechanisms underlying the adverse effects of exposure to MC-LR in Chinese hamster ovary (CHO) cells. The results showed that MC-LR inhibited the in vitro proliferation of CHO cells significantly, with an IC50 of 10 μM. Moreover, MC-LR-treated CHO cells revealed strong induction of cell cycle arrest and apoptosis...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27874078/glutamate-dehydrogenase-activator-bch-stimulating-reductive-amination-prevents-high-fat-high-fructose-diet-induced-steatohepatitis-and-hyperglycemia-in-c57bl-6j-mice
#14
Seung Jin Han, Sung-E Choi, Sang-A Yi, Jong Gab Jung, Ik-Rak Jung, Maureen Shin, Seok Kang, Hyunhee Oh, Hae Jin Kim, Dae Jung Kim, Ji Eun Kwon, Cheol Soo Choi, Kwan Woo Lee, Yup Kang
Individuals with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D) induced by high calorie western diet are characterized by enhanced lipogenesis and gluconeogenesis in the liver. Stimulation of reductive amination may shift tricarboxylic acid cycle metabolism for lipogenesis and gluconeogenesis toward glutamate synthesis with increase of NAD+/NADH ratio and thus, ameliorate high calorie diet-induced fatty liver and hyperglycemia. Stimulation of reductive amination through glutamate dehydrogenase (GDH) activator 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) reduced both de novo lipogenesis and gluconeogenesis but increased the activities of sirtuins and AMP-activated kinase in primary hepatocytes...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27874009/corrigendum-regulation-of-perk-eif2%C3%AE-signalling-by-tuberous-sclerosis-complex-1-controls-homoeostasis-and-survival-of-myelinating-oligodendrocytes
#15
Minqing Jiang, Lei Liu, Xuelian He, Haibo Wang, Wensheng Lin, Huimin Wang, Sung O Yoon, Teresa L Wood, Q Richard Lu
No abstract text is available yet for this article.
November 22, 2016: Nature Communications
https://www.readbyqxmd.com/read/27871651/erk-activated-by-histamine-h1-receptor-is-anti-proliferative-through-spatial-restriction-in-the-cytosol
#16
Ruchi Jain, Uchenna Watson, Deepak Kumar Saini
Histamine, a primary mediator of allergic responses, elicits its effects by activating specific receptors belonging to the GPCR family in target cells. Activation of histamine receptor can activate MAP kinases as recorded by monitoring the phosphorylation of extracellular signal regulated kinase (ERK). Despite this, ERK phosphorylation does not translate into pro-proliferative changes after histamine stimulation in HeLa cells. Here we show that histamine H1 receptor activation mediates MAPK activation through PLCβ, Src, PKCδ and MEK pathway, but does not lead to nuclear relocalization of phospho-ERK (pERK), classically associated with pro-proliferative changes...
October 25, 2016: European Journal of Cell Biology
https://www.readbyqxmd.com/read/27868197/expression-of-a-hepatitis-b-virus-pre-s2-deletion-mutant-in-the-liver-results-in-hepatomegaly-and-hepatocellular-carcinoma-in-mice
#17
Yuan-Chi Teng, Jenq Chyuan Neo, Jaw-Ching Wu, Yi-Fan Chen, Cheng-Heng Kao, Ting-Fen Tsai
Hepatocellular carcinoma (HCC) is the most common form of liver cancer and has a poor prognosis and a low survival rate; its incidence is on the rise. Hepatitis B virus (HBV) infection is one of the main causes of HCC. A high prevalence of pre-S deletions of HBV surface antigen, which encompass T-cell and/or B-cell epitopes, is found in HBV carriers; antiviral therapy and viral immune escape may cause and select for these HBV mutants. In particular, the presence of pre-S2 deletion mutants is an important risk factor associated with cirrhosis and HCC...
November 21, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27867349/baclofen-protects-primary-rat-retinal-ganglion-cells-from-chemical-hypoxia-induced-apoptosis-through-the-akt-and-perk-pathways
#18
Pingping Fu, Qiang Wu, Jianyan Hu, Tingting Li, Fengjuan Gao
Retinal ganglion cells (RGCs) consume large quantities of energy to convert light information into a neuronal signal, which makes them highly susceptible to hypoxic injury. This study aimed to investigate the potential protection by baclofen, a GABAB receptor agonist of RGCs against hypoxia-induced apoptosis. Cobalt chloride (CoCl2) was applied to mimic hypoxia. Primary rat RGCs were subjected to CoCl2 with or without baclofen treatment, and RNA interference techniques were used to knock down the GABAB2 gene in the primary RGCs...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27863885/cell-type-specific-variation-in-the-induction-of-er-stress-and-downstream-events-in-chikungunya-virus-infection
#19
Sarawut Khongwichit, Nitwara Wikan, Bizunesh Abere, Chutima Thepparit, Atichat Kuadkitkan, Sukathida Ubol, Duncan R Smith
Over the last decade infections with the mosquito transmitted chikungunya virus (CHIKV) have become a major worldwide concern, and considerable efforts have been made in understanding the interaction of this virus with the host cell machinery. Studies have documented the induction of the unfolded protein response (UPR), as well as the induction of apoptosis and autophagy in response to CHIKV infection. This study comparatively analysed these three processes in two cell lines, Hela and HepG2. Infection of Hela cells was characterized by activation of the PERK/eIF2α branch of the UPR, the induction of autophagy and early apoptosis, while infection of HepG2 cells was characterized by activation of the IRE/XBP1 branch of the UPR, limited or no activation of autophagy and comparatively later apoptosis...
November 15, 2016: Microbial Pathogenesis
https://www.readbyqxmd.com/read/27863427/sorafenib-pretreatment-enhances-radiotherapy-through-targeting-mek-erk-nf-%C3%AE%C2%BAb-pathway-in-human-hepatocellular-carcinoma-bearing-mouse-model
#20
John Chun-Hao Chen, Hui-Yen Chuang, Fei-Ting Hsu, Yi-Chen Chen, Yi-Chun Chien, Jeng-Jong Hwang
Patients with unresectable hepatocellular carcinoma (HCC) usually have poor prognosis because current monotherapy including surgery, chemotherapy and radiotherapy (RT) are not effective. Combination therapy may be effective to overcome this clinical problem. Here, we proposed the combination of sorafenib and RT, which have been applied in HCC treatment, could improve the treatment outcome of HCC. Our previous study showed that sorafenib could suppress the expression of NF-κB which is related to the chemo- and radio-resistance...
November 16, 2016: Oncotarget
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