Endoplasmic reticulum stress response
in the roadway for the effects of non-steroidal
anti-inflammatory drugs

• Authors: Fernanda L.B. Mügge , Aristóbolo M. Silva
• Languages of publication: EN

Abstracts

EN

Over the past decade, a handful of evidence
has been provided that nonsteroidal anti-inflammatory
drugs (NSAIDs) display effects on the homeostasis of
the endoplasmic reticulum (ER). Their uptake into cells
will eventually lead to activation or inhibition of key
molecules that mediate ER stress responses, raising not
only a growing interest for a pharmacological target in
ER stress responses but also important questions how
the ER-stress mediated effects induced by NSAIDs could
be therapeutically advantageous or not. We review here
the toxicity effects and therapeutic applications of NSAIDs
involving the three majors ER stress arms namely PERK,
IRE1, and ATF6. First, we provide brief introduction on
the well-established and characterized downstream
events mediated by these ER stress players, followed
by presentation of the NSAIDs compounds and mode of
action, and finally their effects on ER stress response.
NSAIDs present promising drug agents targeting the
components of ER stress in different aspects of cancer
and other diseases, but a better comprehension of the
mechanisms underlying their benefits and harms will
certainly pave the road for several diseases’ therapy.

Keywords

EN

NSAIDs; PERK; IRE1; ATF6; CHOP; GRP78; XBP1; cancer cells

• Publisher: De Gruyter Open
• Journal: Endoplasmic Reticulum Stress in Diseases
• Year: 2015
• Volume: 2
• Issue: 1

Dates

accepted

15 - 12 - 2014

online

24 - 2 - 2015

received

30 - 8 - 2014

Contributors

author

Fernanda L.B. Mügge

• Laboratory of Inflammatory Genes, Institute
  of Biological Sciences, Federal University of Minas Gerais, Belo
  Horizonte, MG, Brazil

author

Aristóbolo M. Silva

• Laboratory of
  Inflammatory Genes, Institute of Biological Sciences, Federal
  University of Minas Gerais – Av. Antonio Carlos, 6627 – UFMG,
  ICB, Rm J3-243. CEP: 31270-901 Belo Horizonte, MG, Brazil

References

• [1] Bertolotti A., Zhang Y., Hendershot L.M., Harding H.P., Ron D.,Dynamic interaction of BiP and ER stress transducers in theunfolded-protein response, Nat Cell Biol, 2000, 2(6), 326-32.
• [2] Shen J., Chen X., Hendershot L., Prywes R., ER stress regulationof ATF6 localization by dissociation of BiP/GRP78 binding andunmasking of Golgi localization signals, Dev Cell, 2002, 3(1),99-111.[Crossref]
• [3] Nadanaka S., Okada T., Yoshida H., Mori K., Role of disulfidebridges formed in the luminal domain of ATF6 in sensingendoplasmic reticulum stress, Mol Cell Biol, 2007, 27(3),1027-43.[Crossref]
• [4] Gardner B.M., Walter P., Unfolded proteins are Ire1-activatingligands that directly induce the unfolded protein response,Science, 2011, 333(6051), 1891-4.
• [5] Volmer R., van der Ploeg K., Ron D., Membrane lipid saturationactivates endoplasmic reticulum unfolded protein responsetransducers through their transmembrane domains, Proc NatlAcad Sci U S A, 2013, 110(12), 4628-33.
• [6] Cunha D.A., Hekerman P., Ladriere L., Bazarra-Castro A., OrtisF., Wakeham M.C., et al., Initiation and execution of lipotoxicER stress in pancreatic beta-cells, J Cell Sci, 2008, 121(Pt 14),2308-18.
• [7] Feng B., Yao P.M., Li Y., Devlin C.M., Zhang D., Harding H.P., et al.,The endoplasmic reticulum is the site of cholesterol-inducedcytotoxicity in macrophages, Nat Cell Biol, 2003, 5(9), 781-92.[Crossref]
• [8] Calfon M., Zeng H., Urano F., Till J.H., Hubbard S.R., Harding H.P.,et al., IRE1 couples endoplasmic reticulum load to secretorycapacity by processing the XBP-1 mRNA, Nature, 2002,415(6867), 92-6.
• [9] Chen X., Shen J., Prywes R., The luminal domain of ATF6 sensesendoplasmic reticulum (ER) stress and causes translocationof ATF6 from the ER to the Golgi, J Biol Chem, 2002, 277(15),13045-52.
• [10] Haze K., Yoshida H., Yanagi H., Yura T., Mori K., Mammaliantranscription factor ATF6 is synthesized as a transmembraneprotein and activated by proteolysis in response toendoplasmic reticulum stress, Mol Biol Cell, 1999, 10(11),3787-99.[Crossref]
• [11] Ye J., Rawson R.B., Komuro R., Chen X., Dave U.P., Prywes R., etal., ER stress induces cleavage of membrane-bound ATF6 bythe same proteases that process SREBPs, Mol Cell, 2000, 6(6),1355-64.[Crossref]
• [12] Kokame K., Kato H., Miyata T., Identification of ERSE-II, anew cis-acting element responsible for the ATF6-dependentmammalian unfolded protein response, J Biol Chem, 2001,276(12), 9199-205.
• [13] Yoshida H., Haze K., Yanagi H., Yura T., Mori K., Identification ofthe cis-acting endoplasmic reticulum stress response elementresponsible for transcriptional induction of mammalianglucose-regulated proteins. Involvement of basic leucine zippertranscription factors, J Biol Chem, 1998, 273(50), 33741-9.
• [14] Yoshida H., Matsui T., Yamamoto A., Okada T., Mori K., XBP1mRNA is induced by ATF6 and spliced by IRE1 in response toER stress to produce a highly active transcription factor, Cell,2001, 107(7), 881-91.
• [15] Yoshida H., Okada T., Haze K., Yanagi H., Yura T., Negishi M.,et al., Endoplasmic reticulum stress-induced formation of transcription factor complex ERSF including NF-Y (CBF) andactivating transcription factors 6alpha and 6beta that activatesthe mammalian unfolded protein response, Mol Cell Biol, 2001,21(4), 1239-48.[Crossref]
• [16] Sato Y., Nadanaka S., Okada T., Okawa K., Mori K., Luminaldomain of ATF6 alone is sufficient for sensing endoplasmicreticulum stress and subsequent transport to the Golgiapparatus, Cell Struct Funct, 2011, 36(1), 35-47.[Crossref]
• [17] Harding H.P., Zeng H., Zhang Y., Jungries R., Chung P.,Plesken H., et al., Diabetes mellitus and exocrine pancreaticdysfunction in perk-/- mice reveals a role for translationalcontrol in secretory cell survival, Mol Cell, 2001, 7(6), 1153-63.[Crossref]
• [18] Harding H.P., Zhang Y., Ron D., Protein translation and foldingare coupled by an endoplasmic-reticulum-resident kinase,Nature, 1999, 397(6716), 271-4.
• [19] Harding H.P., Zhang Y., Bertolotti A., Zeng H., Ron D., Perk isessential for translational regulation and cell survival duringthe unfolded protein response, Mol Cell, 2000, 5(5), 897-904.[Crossref]
• [20] Harding H.P., Zhang Y., Zeng H., Novoa I., Lu P.D., Calfon M.,et al., An integrated stress response regulates amino acidmetabolism and resistance to oxidative stress, Mol Cell, 2003,11(3), 619-33.[Crossref]
• [21] Vattem K.M., Wek R.C., Reinitiation involving upstream ORFsregulates ATF4 mRNA translation in mammalian cells, Proc NatlAcad Sci U S A, 2004, 101(31), 11269-74.
• [22] McCullough K.D., Martindale J.L., Klotz L.O., Aw T.Y., HolbrookN.J., Gadd153 sensitizes cells to endoplasmic reticulum stressby down-regulating Bcl2 and perturbing the cellular redoxstate, Mol Cell Biol, 2001, 21(4), 1249-59.[Crossref]
• [23] Brunton L.L., Chabner B.A., Knollman B.C., Goodman andGilman’s the pharmacological basis of therapeutics, 2011,1808p.
• [24] Bacchi S., Palumbo P., Sponta A., Coppolino M.F., Clinicalpharmacology of non-steroidal anti-inflammatory drugs: areview, Antiinflamm Antiallergy Agents Med Chem, 2012, 11(1),52-64.
• [25] Abdel-Tawab M., Zettl H., Schubert-Zsilavecz M., Nonsteroidalanti-inflammatory drugs: a critical review on current conceptsapplied to reduce gastrointestinal toxicity, Curr Med Chem,2009, 16(16), 2042-63.[Crossref]
• [26] Chandrasekharan N.V., Dai H., Roos K.L., Evanson N.K., TomsikJ., Elton T.S., et al., COX-3, a cyclooxygenase-1 variant inhibitedby acetaminophen and other analgesic/antipyretic drugs:cloning, structure, and expression, Proc Natl Acad Sci U S A,2002, 99(21), 13926-31.[Crossref]
• [27] Kis B., Snipes J.A., Busija D.W., Acetaminophen and thecyclooxygenase-3 puzzle: sorting out facts, fictions, anduncertainties, J Pharmacol Exp Ther, 2005, 315(1), 1-7.
• [28] Lee Y.S., Kim H., Brahim J.S., Rowan J., Lee G., Dionne R.A.,Acetaminophen selectively suppresses peripheral prostaglandinE2 release and increases COX-2 gene expression ina clinical model of acute inflammation, Pain, 2007, 129(3),279-86.
• [29] Hinz B., Cheremina O., Brune K., Acetaminophen (paracetamol)is a selective cyclooxygenase-2 inhibitor in man, Faseb J, 2008,22(2), 383-90.
• [30] Stone E., An account of the success of the bark of the willowtree in the cure of agues. In a letter to the high honourableGeorge Earl of Macclesfield, President of R. S. from the Rev.Mr. Edmund Stone, of Chipping-Norton in Oxfordshire.,Philosophical Transactions, 1763, 53.
• [31] Amann R., Peskar B.A., Anti-inflammatory effects of aspirin andsodium salicylate, Eur J Pharmacol, 2002, 447(1), 1-9.
• [32] Vainio H., Morgan G., Aspirin for the second hundred years: newuses for an old drug, Pharmacol Toxicol, 1997, 81(4), 151-2.[Crossref]
• [33] Alhusaini S., McGee K., Schisano B., Harte A., McTernanP., Kumar S., et al., Lipopolysaccharide, high glucose andsaturated fatty acids induce endoplasmic reticulum stress incultured primary human adipocytes: Salicylate alleviates thisstress, Biochem Biophys Res Commun, 2010, 397(3), 472-8.
• [34] Silva A.M., Wang D., Komar A.A., Castilho B.A., Williams B.R.,Salicylates trigger protein synthesis inhibition in a proteinkinase R-like endoplasmic reticulum kinase-dependentmanner, J Biol Chem, 2007, 282(14), 10164-71.
• [35] Gentz S.H., Bertollo C.M., Souza-Fagundes E.M., da Silva A.M.,Implication of eIF2alpha kinase GCN2 in induction of apoptosisand endoplasmic reticulum stress-responsive genes by sodiumsalicylate, J Pharm Pharmacol, 2013, 65(3), 430-40.
• [36] Mehta D., Bhargava D.K., Non-steroidal anti inflammatory drugsand gastrointestinal toxicity, Apollo Medicine, 2010, 7(4),251-62.[Crossref]
• [37] Boelsterli U.A., Redinbo M.R., Saitta K.S., Multiple NSAIDinducedhits injure the small intestine: underlying mechanismsand novel strategies, Toxicol Sci, 2012, 131(2), 654-67.
• [38] Wallace J.L., McKnight W., Reuter B.K., Vergnolle N., NSAIDinducedgastric damage in rats: requirement for inhibition ofboth cyclooxygenase 1 and 2, Gastroenterology, 2000, 119(3),706-14.
• [39] Langenbach R., Morham S.G., Tiano H.F., Loftin C.D.,Ghanayem B.I., Chulada P.C., et al., Prostaglandin synthase1 gene disruption in mice reduces arachidonic acid-inducedinflammation and indomethacin-induced gastric ulceration,Cell, 1995, 83(3), 483-92.[Crossref]
• [40] Tomisato W., Tsutsumi S., Hoshino T., Hwang H.J., Mio M.,Tsuchiya T., et al., Role of direct cytotoxic effects of NSAIDs inthe induction of gastric lesions, Biochem Pharmacol, 2004,67(3), 575-85.[Crossref]
• [41] Tomisato W., Tsutsumi S., Rokutan K., Tsuchiya T., MizushimaT., NSAIDs induce both necrosis and apoptosis in guineapig gastric mucosal cells in primary culture, Am J PhysiolGastrointest Liver Physiol, 2001, 281(4), G1092-100.
• [42] Tsutsumi S., Gotoh T., Tomisato W., Mima S., Hoshino T., HwangH.J., et al., Endoplasmic reticulum stress response is involvedin nonsteroidal anti-inflammatory drug-induced apoptosis, CellDeath Differ, 2004, 11(9), 1009-16.[Crossref]
• [43] Ohyama K., Shiokawa A., Ito K., Masuyama R., IchibangaseT., Kishikawa N., et al., Toxicoproteomic analysis of a mousemodel of nonsteroidal anti-inflammatory drug-induced gastriculcers, Biochem Biophys Res Commun, 2012, 420(1), 210-5.
• [44] Pereira-Leite C., Nunes C., Reis S., Interaction of nonsteroidalanti-inflammatory drugs with membranes: in vitro assessmentand relevance for their biological actions, Prog Lipid Res, 2013,52(4), 571-84.[Crossref]
• [45] Tanaka K., Tomisato W., Hoshino T., Ishihara T., Namba T.,Aburaya M., et al., Involvement of intracellular Ca2+ levels innonsteroidal anti-inflammatory drug-induced apoptosis, J BiolChem, 2005, 280(35), 31059-67.
• [46] Ishihara T., Hoshino T., Namba T., Tanaka K., MizushimaT., Involvement of up-regulation of PUMA in non-steroidal anti-inflammatory drug-induced apoptosis, Biochem BiophysRes Commun, 2007, 356(3), 711-7.
• [47] Pyrko P., Kardosh A., Schonthal A.H., Celecoxib transientlyinhibits cellular protein synthesis, Biochem Pharmacol, 2008,75(2), 395-404.[Crossref]
• [48] Tsutsumi S., Namba T., Tanaka K.I., Arai Y., Ishihara T., AburayaM., et al., Celecoxib upregulates endoplasmic reticulumchaperones that inhibit celecoxib-induced apoptosis in humangastric cells, Oncogene, 2006, 25(7), 1018-29.[Crossref]
• [49] Namba T., Hoshino T., Suemasu S., Takarada-Iemata M., Hori O.,Nakagata N., et al., Suppression of expression of endoplasmicreticulum chaperones by Helicobacter pylori and its role inexacerbation of non-steroidal anti-inflammatory drug-inducedgastric lesions, J Biol Chem, 2010, 285(48), 37302-13.
• [50] Namba T., Hoshino T., Tanaka K., Tsutsumi S., Ishihara T., MimaS., et al., Up-regulation of 150-kDa oxygen-regulated proteinby celecoxib in human gastric carcinoma cells, Mol Pharmacol,2007, 71(3), 860-70.
• [51] Teoh N.C., Farrell G.C., Hepatotoxicity associated withnon-steroidal anti-inflammatory drugs, Clin Liver Dis, 2003,7(2), 401-13.[Crossref]
• [52] Unzueta A., Vargas H.E., Nonsteroidal anti-inflammatorydrug-induced hepatoxicity, Clin Liver Dis, 2013, 17(4), 643-56,ix.[Crossref]
• [53] Nadanaciva S., Aleo M.D., Strock C.J., Stedman D.B., Wang H.,Will Y., Toxicity assessments of nonsteroidal anti-inflammatorydrugs in isolated mitochondria, rat hepatocytes, and zebrafishshow good concordance across chemical classes, Toxicol ApplPharmacol, 2013, 272(2), 272-80.[Crossref]
• [54] Franceschelli S., Moltedo O., Amodio G., Tajana G., RemondelliP., In the Huh7 Hepatoma Cells Diclofenac and IndomethacinActivate Differently the Unfolded Protein Response and InduceER Stress Apoptosis, Open Biochem J, 2011, 5, 45-51.[Crossref]
• [55] El-Hassan H., Anwar K., Macanas-Pirard P., Crabtree M., ChowS.C., Johnson V.L., et al., Involvement of mitochondria inacetaminophen-induced apoptosis and hepatic injury: roles ofcytochrome c, Bax, Bid, and caspases, Toxicol Appl Pharmacol,2003, 191(2), 118-29.
• [56] Nagy G., Kardon T., Wunderlich L., Szarka A., Kiss A., SchaffZ., et al., Acetaminophen induces ER dependent signaling inmouse liver, Arch Biochem Biophys, 2007, 459(2), 273-9.
• [57] Hur K.Y., So J.S., Ruda V., Frank-Kamenetsky M., FitzgeraldK., Koteliansky V., et al., IRE1alpha activation protects miceagainst acetaminophen-induced hepatotoxicity, J Exp Med,2012, 209(2), 307-18.
• [58] Uzi D., Barda L., Scaiewicz V., Mills M., Mueller T., Gonzalez-Rodriguez A., et al., CHOP is a critical regulator ofacetaminophen-induced hepatotoxicity, J Hepatol, 2013, 59(3),495-503.[Crossref]
• [59] Lorz C., Justo P., Sanz A., Subira D., Egido J., Ortiz A.,Paracetamol-induced renal tubular injury: a role for ER stress, JAm Soc Nephrol, 2004, 15(2), 380-9.[Crossref]
• [60] Kalinec G.M., Thein P., Parsa A., Yorgason J., Luxford W., UrrutiaR., et al., Acetaminophen and NAPQI are toxic to auditory cellsvia oxidative and endoplasmic reticulum stress-dependentpathways, Hear Res, 2014, 313, 26-37.
• [61] Grosch S., Maier T.J., Schiffmann S., Geisslinger G.,Cyclooxygenase-2 (COX-2)-independent anticarcinogeniceffects of selective COX-2 inhibitors, J Natl Cancer Inst, 2006,98(11), 736-47.
• [62] Koki A.T., Masferrer J.L., Celecoxib: a specific COX-2 inhibitorwith anticancer properties, Cancer Control, 2002, 9(2 Suppl),28-35.
• [63] Liggett J.L., Zhang X., Eling T.E., Baek S.J., Anti-tumor activityof non-steroidal anti-inflammatory drugs: cyclooxygenaseindependenttargets, Cancer Lett, 2014, 346(2), 217-24.
• [64] Chuang H.C., Kardosh A., Gaffney K.J., Petasis N.A., SchonthalA.H., COX-2 inhibition is neither necessary nor sufficientfor celecoxib to suppress tumor cell proliferation and focusformation in vitro, Mol Cancer, 2008, 7, 38.
• [65] Chen S.T., Thomas S., Gaffney K.J., Louie S.G., Petasis N.A.,Schonthal A.H., Cytotoxic effects of celecoxib on Raji lymphomacells correlate with aggravated endoplasmic reticulum stressbut not with inhibition of cyclooxygenase-2, Leuk Res, 2010,34(2), 250-3.[Crossref]
• [66] Johnson A.J., Hsu A.L., Lin H.P., Song X., Chen C.S., The cyclooxygenase-2 inhibitor celecoxib perturbs intracellular calciumby inhibiting endoplasmic reticulum Ca2+-ATPases: a plausiblelink with its anti-tumour effect and cardiovascular risks,Biochem J, 2002, 366(Pt 3), 831-7.
• [67] Cha W., Park S.W., Kwon T.K., Hah J.H., Sung M.W., Endoplasmicreticulum stress response as a possible mechanism ofcyclooxygenase-2-independent anticancer effect of celecoxib,Anticancer Res, 2014, 34(4), 1731-5.
• [68] Pyrko P., Kardosh A., Liu Y.T., Soriano N., Xiong W., Chow R.H.,et al., Calcium-activated endoplasmic reticulum stress as amajor component of tumor cell death induced by 2,5-dimethylcelecoxib,a non-coxib analogue of celecoxib, Mol Cancer Ther,2007, 6(4), 1262-75.[Crossref]
• [69] Du H., Li W., Wang Y., Chen S., Zhang Y., Celecoxib induces cellapoptosis coupled with up-regulation of the expression of VEGFby a mechanism involving ER stress in human colorectal cancercells, Oncol Rep, 2011, 26(2), 495-502.
• [70] Huang K.H., Kuo K.L., Chen S.C., Weng T.I., Chuang Y.T., TsaiY.C., et al., Down-regulation of glucose-regulated protein (GRP)78 potentiates cytotoxic effect of celecoxib in human urothelialcarcinoma cells, PLoS One, 2012, 7(3), e33615.[Crossref]
• [71] Zhang X., Lee S.H., Min K.W., McEntee M.F., Jeong J.B., Li Q.,et al., The involvement of endoplasmic reticulum stress in thesuppression of colorectal tumorigenesis by tolfenamic acid,Cancer Prev Res (Phila), 2013, 6(12), 1337-47.[Crossref]
• [72] Namba T., Ishihara T., Tanaka K., Hoshino T., Mizushima T.,Transcriptional activation of ATF6 by endoplasmic reticulumstressors, Biochem Biophys Res Commun, 2007, 355(2), 543-8.
• [73] Ikegaki N., Hicks S.L., Regan P.L., Jacobs J., Jumbo A.S.,Leonhardt P., et al., S(+)-ibuprofen destabilizes MYC/MYCN andAKT, increases p53 expression, and induces unfolded proteinresponse and favorable phenotype in neuroblastoma cell lines,Int J Oncol, 2014, 44(1), 35-43.
• [74] Ou Y.C., Yang C.R., Cheng C.L., Raung S.L., Hung Y.Y., Chen C.J.,Indomethacin induces apoptosis in 786-O renal cell carcinomacells by activating mitogen-activated protein kinases and AKT,Eur J Pharmacol, 2007, 563(1-3), 49-60.
• [75] Kim B.M., Maeng K., Lee K.H., Hong S.H., Combined treatmentwith the Cox-2 inhibitor niflumic acid and PPARgamma ligandciglitazone induces ER stress/caspase-8-mediated apoptosis inhuman lung cancer cells, Cancer Lett, 2011, 300(2), 134-44.
• [76] Yang H., Park S.H., Choi H.J., Moon Y., The integrated stressresponse-associated signals modulates intestinal tumor cell growth by NSAID-activated gene 1 (NAG-1/MIC-1/PTGF-beta),Carcinogenesis, 2010, 31(4), 703-11.[Crossref]
• [77] White M.C., Johnson G.G., Zhang W., Hobrath J.V., Piazza G.A.,Grimaldi M., Sulindac sulfide inhibits sarcoendoplasmicreticulum Ca2+ ATPase, induces endoplasmic reticulumstress response, and exerts toxicity in glioma cells: relevantsimilarities to and important differences from celecoxib, JNeurosci Res, 2013, 91(3), 393-406.[Crossref]
• [78] Kardosh A., Golden E.B., Pyrko P., Uddin J., Hofman F.M., ChenT.C., et al., Aggravated endoplasmic reticulum stress as abasis for enhanced glioblastoma cell killing by bortezomibin combination with celecoxib or its non-coxib analogue,2,5-dimethyl-celecoxib, Cancer Res, 2008, 68(3), 843-51.
• [79] Cusimano A., Azzolina A., Iovanna J.L., Bachvarov D., McCubreyJ.A., D’Alessandro N., et al., Novel combination of celecoxib andproteasome inhibitor MG132 provides synergistic antiproliferativeand proapoptotic effects in human liver tumor cells,Cell Cycle, 2010, 9(7), 1399-410.
• [80] Cho H.Y., Thomas S., Golden E.B., Gaffney K.J., Hofman F.M.,Chen T.C., et al., Enhanced killing of chemo-resistant breastcancer cells via controlled aggravation of ER stress, Cancer Lett,2009, 282(1), 87-97.
• [81] Booth L., Roberts J.L., Cruickshanks N., Tavallai S., Webb T.,Samuel P., et al., PDE5 inhibitors enhance Celecoxib killing inmultiple tumor types, J Cell Physiol, 2014.
• [82] Amaravadi R.K., Thompson C.B., The roles of therapy-inducedautophagy and necrosis in cancer treatment, Clin Cancer Res,2007, 13(24), 7271-9.[Crossref]
• [83] Jin S., White E., Role of autophagy in cancer: management ofmetabolic stress, Autophagy, 2007, 3(1), 28-31.[Crossref]
• [84] Thomas S., Sharma N., Golden E.B., Cho H., Agarwal P., GaffneyK.J., et al., Preferential killing of triple-negative breast cancercells in vitro and in vivo when pharmacological aggravators ofendoplasmic reticulum stress are combined with autophagyinhibitors, Cancer Lett, 2012, 325(1), 63-71.
• [85] Ozcan U., Cao Q., Yilmaz E., Lee A.H., Iwakoshi N.N., OzdelenE., et al., Endoplasmic reticulum stress links obesity, insulinaction, and type 2 diabetes, Science, 2004, 306(5695), 457-61.
• [86] Hosoi T., Yamaguchi R., Noji K., Matsuo S., Baba S., Toyoda K.,et al., Flurbiprofen ameliorated obesity by attenuating leptinresistance induced by endoplasmic reticulum stress, EMBO MolMed, 2014, 6(3), 335-46.
• [87] Matus S., Glimcher L.H., Hetz C., Protein folding stress inneurodegenerative diseases: a glimpse into the ER, Curr OpinCell Biol, 2011, 23(2), 239-52.[Crossref]
• [88] Hetz C., Mollereau B., Disturbance of endoplasmic reticulumproteostasis in neurodegenerative diseases, Nat Rev Neurosci,2014, 15(4), 233-49.[Crossref]
• [89] Yamazaki T., Muramoto M., Oe T., Morikawa N., OkitsuO., Nagashima T., et al., Diclofenac, a non-steroidalanti-inflammatory drug, suppresses apoptosis inducedby endoplasmic reticulum stresses by inhibiting caspasesignaling, Neuropharmacology, 2006, 50(5), 558-67.[Crossref]
• [90] Hosoi T., Sasaki M., Baba S., Ozawa K., Effect of pranoprofen onendoplasmic reticulum stress in the primary cultured glial cells,Neurochem Int, 2009, 54(1), 1-6.[Crossref]
• [91] Llorente I.L., Burgin T.C., Perez-Rodriguez D., Martinez-Villayandre B., Perez-Garcia C.C., Fernandez-Lopez A.,Unfolded protein response to global ischemia following 48 h ofreperfusion in the rat brain: the effect of age and meloxicam, JNeurochem, 2013, 127(5), 701-10.
• [92] Ye Z., Wang N., Xia P., Wang E., Liao J., Guo Q., Parecoxibsuppresses CHOP and Foxo1 nuclear translocation, butincreases GRP78 levels in a rat model of focal ischemia,Neurochem Res, 2013, 38(4), 686-93. [Crossref]

Identifiers

DOI

10.1515/ersc-2015-0001