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https://www.readbyqxmd.com/read/29236949/seipin-deficiency-leads-to-increased-er-stress-and-apoptosis-in-mammary-gland-alveolar-epithelial-cells-during-lactation
#1
Ahmed E El Zowalaty, Rong Li, Weiqin Chen, Xiaoqin Ye
Seipin is an integral endoplasmic reticulum (ER) membrane protein encoded by Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2/Bscl2) gene. Most litters (59%) from Bscl2-/- dams mated with WT (Bscl2+/+) males didn't survive PND5 and pups (Bscl2+/-) lacked milk in their stomachs. The survived litters had reduced pup survival rate at PND21. It was hypothesized that seipin was critical for lactation. Bscl2 was upregulated and highly detected in the lactation day 1 (LD1) WT mammary gland alveolar epithelial cells...
December 11, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29235240/gender-differences-in-first-self-perceived-signs-and-symptoms-in-patients-with-an-at-risk-mental-state-and-first-episode-psychosis
#2
Ulrike Heitz, Erich Studerus, Stephanie Menghini-Müller, Martina Papmeyer, Laura Egloff, Sarah Ittig, Astrid Navarra, Christina Andreou, Anita Riecher-Rössler
AIM: Gender differences in the current symptomatology of patients with psychotic disorders have previously been described in the literature. However, it has not yet been investigated whether gender differences exist in the very first self-perceived signs or symptoms of illness onset. The aim of this study was to investigate this aspect in at-risk mental state (ARMS) and first-episode psychosis (FEP) patients. METHODS: ARMS and FEP were recruited via the early detection of psychosis (FePsy) clinic Basel, Switzerland...
December 13, 2017: Early Intervention in Psychiatry
https://www.readbyqxmd.com/read/29207638/jolkinolide-b-induces-apoptosis-of-colorectal-carcinoma-through-ros-er-stress-ca2-mitochondria-dependent-pathway
#3
Jing Zhang, Yang Wang, Ye Zhou, Qing-Yu He
Colorectal carcinoma (CRC) remains one of the leading causes of death in cancer-related diseases. In this study, we aimed to investigate the anticancer effect of Jolkinolide B (JB), a bioactive diterpenoid component isolated from the dried roots of Euphorbia fischeriana Steud, on CRC cells and its underlying mechanisms. We found that JB suppressed the cell viability and colony formation of CRC cells, HT29 and SW620. Annexin V/PI assay revealed that JB induced apoptosis in CRC cells, which was further confirmed by the increased expression of cleaved-caspase3 and cleaved-PARP...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207602/the-trpv1-ion-channel-regulates-thymocyte-differentiation-by-modulating-autophagy-and-proteasome-activity
#4
Consuelo Amantini, Valerio Farfariello, Claudio Cardinali, Maria Beatrice Morelli, Oliviero Marinelli, Massimo Nabissi, Matteo Santoni, Laura Bonfili, Valentina Cecarini, Anna Maria Eleuteri, Giorgio Santoni
Autophagy and the ubiquitin-proteasome system (UPS) control thymus cell homeostasis under resting and endoplasmic reticulum (ER) stress conditions. Several evidence support a cross-talk between UPS and autophagy; abrogation of UPS responses stimulates autophagy, and vice versa the inhibition of autophagy alters the UPS functions. Herein, we found that TRPV1 activation induces ER stress, proteasome dysfunction and autophagy in thymocytes by modulating the expression of UPR-related genes. The TRPV1-mediated autophagy prevents the UPR activation by inhibiting BiP, Grp94 and ERp57 chaperone protein expression...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29205766/the-bile-salt-sodium-taurocholate-induces-campylobacter-jejuni-outer-membrane-vesicle-production-and-increases-omv-associated-proteolytic-activity
#5
Abdi Elmi, Amber Dorey, Eleanor Watson, Heena Jagatia, Neil F Inglis, Ozan Gundogdu, Mona Bajaj-Elliott, Brendan W Wren, David G E Smith, Nick Dorrell
Campylobacter jejuni, the leading cause of bacterial acute gastroenteritis worldwide, secretes an arsenal of virulence-associated proteins within outer membrane vesicles (OMVs). C. jejuni OMVs contain three serine proteases (HtrA, Cj0511 and Cj1365c) which cleave the intestinal epithelial cell (IEC) tight and adherens junction proteins occludin and E-cadherin, promoting enhanced C. jejuni adhesion to and invasion of IECs. C. jejuni OMVs also induce IECs innate immune responses. The bile salt sodium taurocholate (ST) is sensed as a host signal to co-ordinate the activation of virulence-associated genes in the enteric pathogen Vibrio cholerae...
December 4, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/29198525/a-j-protein-co-chaperone-recruits-bip-to-monomerize-ire1-and-repress-the-unfolded-protein-response
#6
Niko Amin-Wetzel, Reuben A Saunders, Maarten J Kamphuis, Claudia Rato, Steffen Preissler, Heather P Harding, David Ron
When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response (UPR) increases ER-protein-folding capacity to restore protein-folding homeostasis. Unfolded proteins activate UPR signaling across the ER membrane to the nucleus by promoting oligomerization of IRE1, a conserved transmembrane ER stress receptor. However, the coupling of ER stress to IRE1 oligomerization and activation has remained obscure. Here, we report that the ER luminal co-chaperone ERdj4/DNAJB9 is a selective IRE1 repressor that promotes a complex between the luminal Hsp70 BiP and the luminal stress-sensing domain of IRE1α (IRE1LD)...
November 30, 2017: Cell
https://www.readbyqxmd.com/read/29185956/diagnostic-value-of-bip-or-anti-bip-antibodies-for-rheumatoid-arthritis-a-meta-analysis
#7
Yuhui Liu, Jinhua Wu, Guanxin Shen, Ping Lei
OBJECTIVES: To evaluate the diagnostic value of BiP or anti-BiP antibodies in patients with rheumatoid arthritis. METHODS: Relevant studies published on PubMed and CNKI from January 1995 to July 2016 were retrieved. Two reviewers independently evaluated studies and QUADAS tool was used to assess the quality of the included studies. A random-effects model was used to combine sensitivity, specificity, positive and negative likelihood ratios and diagnostic odds ratio...
November 28, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/29182689/a-novel-strategy-to-construct-janus-metallamacrocycles-with-both-a-ru-arene-face-and-an-imidazolium-face
#8
Ji Li, Peipei Zhang, Yan Xu, Zhi Su, Yong Qian, Shunli Li, Tao Yu, Peter J Sadler, Hong-Ke Liu
The bottom-up construction of highly functional metallamacrocycles from simple building blocks is a challenge of much current interest. We have used solvothermal reactions of a bifunctional p-bitmb ligand with [Ru(arene)X2]2 in CH2Cl2 or CH2Br2 to generate the novel mononuclear metallamacrocyclic [RuX(arene)L2CH2]X3 complexes 1-3 (1, arene = p-cym, X = Cl; 2, arene = bip, X = Cl; 3, arene = p-cym, X = Br), which were characterized by various techniques. These complexes are "bowl-like" and have two faces: one coordinative Ru centre (arene)Ru(N,N)X bridged by L (L = 1,4-bis(imidazol-1-ylmethyl)-2,3,5,6-tetramethylbenzene, p-bitmb) to a dipositive bis-imidazolinium centre...
November 28, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29179452/novel-galeterone-analogs-act-independently-of-ar-and-ar-v7-for-the-activation-of-the-unfolded-protein-response-and-induction-of-apoptosis-in-the-cwr22rv1-prostate-cancer-cell-model
#9
David J McCarty, Weiliang Huang, Maureen A Kane, Puranik Purushottamachar, Lalji K Gediya, Vincent C O Njar
The androgen receptor (AR) has long been the primary target for the treatment of prostate cancer (PC). Despite continuous efforts to block AR activity through ligand depletion, AR antagonism, AR depletion and combinations thereof, advanced PC tumors remain resilient. Herein, we evaluate two galeterone analogs, VNPT-178 and VNLG-74A, in PC cell models of diverse androgen and AR dependence attempting to delineate their mechanisms of action and potential clinical utility. Employing basic biochemical techniques, we determined that both analogs have improved antiproliferative and anti-AR activities compared to FDA-approved abiraterone and enzalutamide...
October 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/29174969/resveratrol-modulates-response-against-acute-inflammatory-stimuli-in-aged-mouse-brain
#10
V Palomera-Ávalos, C Griñán-Ferré, V Izquierdo, A Camins, C Sanfeliu, A M Canudas, M Pallàs
With upcoming age, the capability to fight against harmful stimuli decreases and the organism becomes more susceptible to infections and diseases. Here, the objective was to demonstrate the effect of dietary resveratrol in aged mice in potentiating brain defenses against LipoPolySaccharide (LPS). Acute LPS injection induced a strong proinflammatory effect in 24-months-old C57/BL6 mice hippocampi, increasing InterLeukin (Il)-6, Tumor Necrosis Factor-alpha (Tnf-α), Il-1β, and C-X-C motif chemokine (Cxcl10) gene expression levels...
November 23, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/29149522/melatonin-improves-the-meiotic-maturation-of-porcine-oocytes-by-reducing-endoplasmic-reticulum-stress-during-in-vitro-maturation
#11
Hyo-Jin Park, Jae-Young Park, Jin-Woo Kim, Seul-Gi Yang, Jae-Min Jung, Min-Ji Kim, Man-Jong Kang, Young Ho Cho, Gabbine Wee, Hee-Young Yang, Bong-Seok Song, Sun-Uk Kim, Deog-Bon Koo
Under endoplasmic reticulum (ER)-stress conditions, the unfolded protein response (UPR) generates a defense mechanism in mammalian cells. The regulation of UPR signaling is important in oocyte maturation, embryo development, and female reproduction of pigs. Recent studies have shown that melatonin plays an important role as an anti-oxidant to improve pig oocyte maturation. However, there is no report on the role of melatonin in the regulation of UPR signaling and ER-stress during in vitro maturation (IVM) of porcine oocytes...
November 17, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/29138806/effect-of-bis-hydroxymethyl-alkanoate-curcuminoid-derivative-mth-3-on-cell-cycle-arrest-apoptotic-and-autophagic-pathway-in-triple-negative-breast-adenocarcinoma-mda-mb-231-cells-an-in-vitro-study
#12
Ling-Chu Chang, Min-Tsang Hsieh, Jai-Sing Yang, Chi-Cheng Lu, Fuu-Jen Tsai, Je-Wei Tsao, Yu-Jen Chiu, Sheng-Chu Kuo, Kuo-Hsiung Lee
Curcumin has been shown to exert potential antitumor activity in vitro and in vivo involved in multiple signaling pathways. However, the application of curcumin is still limited because of its poor hydrophilicity and low bio-availability. In the present study, we investigated the therapeutic effects of a novel and water soluble bis(hydroxymethyl) alkanoate curcuminoid derivative, MTH-3, on human breast adenocarcinoma MDA-MB-231 cells. This study investigated the effect of MTH-3 on cell viability, cell cycle and induction of autophagy and apoptosis in MDA-MB-231 cells...
November 14, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29138212/bax-inhibiting-peptide-attenuates-bleomycin-induced-lung-injury-in-mice
#13
Kunihiro Suzuki, Toyoshi Yanagihara, Tetsuya Yokoyama, Takashige Maeyama, Saiko Ogata-Suetsugu, Masako Arimura-Omori, Hironori Mikumo, Naoki Hamada, Eiji Harada, Kazuyoshi Kuwano, Taishi Harada, Yoichi Nakanishi
Rationale: Bax is a pro-apoptotic member of the Bcl-2 family of proteins, and plays a central role in mitochondria-dependent apoptosis. Several lines of evidence have implied that Bax is involved in both epithelial apoptosis and fibroblast proliferation in idiopathic pulmonary fibrosis; however, the mechanisms remain unknown. Bax-inhibiting peptide V5 (BIP-V5) exhibits membrane permeability and inhibits the activation of Bax.Objective: The purpose of this study was to investigate whether the control of Bax activity by BIP-V5 reduces the degree of bleomycin-induced lung injury...
November 14, 2017: Biology Open
https://www.readbyqxmd.com/read/29137221/anti-pancreatic-cancer-activity-of-onc212-involves-the-unfolded-protein-response-upr-and-is-reduced-by-igf1-r-and-grp78-bip
#14
Avital Lev, Amriti R Lulla, Jessica Wagner, Marie D Ralff, Joshua B Kiehl, Yan Zhou, Cyril H Benes, Varun V Prabhu, Wolfgang Oster, Igor Astsaturov, David T Dicker, Wafik S El-Deiry
Pancreatic cancer is chemo-resistant and metastasizes early with an overall five-year survival of ∼8.2%. First-in-class imipridone ONC201 is a small molecule in clinical trials with anti-cancer activity. ONC212, a fluorinated-ONC201 analogue, shows preclinical efficacy in melanoma and hepatocellular-cancer models. We investigated efficacy of ONC201 and ONC212 against pancreatic cancer cell lines (N=16 including 9 PDX-cell lines). We demonstrate ONC212 efficacy in 4 in-vivo models including ONC201-resistant tumors...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29131958/design-synthesis-and-biological-assessment-of-biased-allosteric-modulation-of-the-urotensin-ii-receptor-using-achiral-1-3-4-benzotriazepin-2-one-turn-mimics
#15
Antoine Douchez, Étienne Billard, Terence Hébert, David Chatenet, William D Lubell
Benzotriazepin-2-ones were designed to mimic the suggested bioactive γ-turn conformation of the Bip-Lys-Tyr tripeptide in Urocontrin ([Bip(4)]URP), which modulates the urotensin II receptor (UT) and differentiates the effects of the endogenous ligands urotensin II (UII) and urotensin II-related peptide (URP). Twenty-six benzotriazepin-2-ones were synthesized by acylation of anthranilate-derived amino ketones with an aza-glycine equivalent, chemoselective nitrogen functionalization and ring closure. Several mimics exhibited selective modulatory effects on hUII- and URP-associated vasoconstriction in an ex-vivo rat aortic ring bioassay...
November 13, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29126419/the-adverse-vascular-effects-of-multi-walled-carbon-nanotubes-mwcnts-to-human-vein-endothelial-cells-huvecs-in-vitro-role-of-length-of-mwcnts
#16
Jimin Long, Yafang Xiao, Liangliang Liu, Yi Cao
BACKGROUND: Increasing evidences indicate that exposure to multi-walled carbon nanotubes (MWCNTs) could induce adverse vascular effects, but the role of length of MWCNTs in determining the toxic effects is less studied. This study investigated the adverse effects of two well-characterized MWCNTs to human umbilical vein endothelial cells (HUVECs). METHODS: The internalization and localization of MWCNTs in HUVECs were examined by using transmission electron microscopy (TEM)...
November 10, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/29125225/baicalein-reduces-oxidative-stress-in-cho-cell-cultures-and-improves-recombinant-antibody-productivity
#17
Tae Kwang Ha, Anders Holmgaard Hansen, Stefan Kol, Helene Faustrup Kildegaard, Gyun Min Lee
Oxidative stress that naturally accumulates in the endoplasmic reticulum (ER) as a result of mitochondrial energy metabolism and protein synthesis can disturb the ER function. Because ER has a responsibility on the protein synthesis and quality control of the secreted proteins, ER homeostasis has to be well maintained. When H2O2, an oxidative stress inducer, was added to recombinant Chinese hamster ovary (rCHO) cell cultures, it reduced cell growth, monoclonal antibody (mAb) production, and galactosylated form of mAb in a dose-dependent manner...
November 10, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/29118419/melatonin-promotes-triacylglycerol-accumulation-via-mt2-receptor-during-differentiation-in-bovine-intramuscular-preadipocytes
#18
Wucai Yang, Keqiong Tang, Yaning Wang, Yingying Zhang, Linsen Zan
Melatonin (N-acetyl-5-methoxytryptamine) is a derivative of tryptophan which is produced and secreted mainly by the pineal gland and regulates a variety of important central and peripheral actions. To examine the potential effects of melatonin on the proliferation and differentiation of bovine intramuscular preadipocytes (BIPs), BIPs were incubated with different concentrations of melatonin. Melatonin supplementation at 1 mM significantly increased peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein (C/EBP) β, and C/EBPα expression and promoted the differentiation of BIPs into adipocytes with large lipid droplets and high cellular triacylglycerol (TAG) levels...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29111234/exacerbation-and-prolongation-of-psoriasiform-inflammation-in-diabetic-obese-mice-a-synergistic-role-of-cxcl5-and-er-stress
#19
Noriko Shimoura, Hiroshi Nagai, Susumu Fujiwara, Haruki Jimbo, Chikako Nishigori
Accumulating evidence suggests that psoriasis is frequently accompanied by metabolic disorders such as obesity and diabetes. However, the mechanisms underlying the association between increased psoriasis severity and concomitant metabolic syndrome have not been fully clarified. Herein, we show that imiquimod-induced psoriasiform inflammation was exacerbated and prolonged in diabetic obese mice compared to that in control mice, accompanied by remarkably increased lesional expressions of Cxcl5 and Il-1b. Notably, a large number of CXCL5(+) Ly6G(+) cells infiltrated the dermis and subcutaneous fat tissue of the diabetic obese mice...
October 27, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29109265/diminished-ost3-dependent-n-glycosylation-of-the-bip-nucleotide-exchange-factor-sil1-is-an-adaptive-response-to-reductive-er-stress
#20
Kofi L P Stevens, Amy L Black, Kelsi M Wells, K Y Benjamin Yeo, Robert F L Steuart, Colin J Stirling, Benjamin L Schulz, Carl J Mousley
BiP (Kar2 in yeast) is an essential Hsp70 chaperone and master regulator of endoplasmic reticulum (ER) function. BiP's activity is regulated by its intrinsic ATPase activity that can be stimulated by two different nucleotide exchange factors, Sil1 and Lhs1. Both Sil1 and Lhs1 are glycoproteins, but how N-glycosylation regulates their function is not known. Here, we show that N-glycosylation of Sil1, but not of Lhs1, is diminished upon reductive stress. N-glycosylation of Sil1 is predominantly Ost3-dependent and requires a functional Ost3 CxxC thioredoxin motif...
November 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
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