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T9033 Sigma

Thapsigargin

≥98% (HPLC), solid film

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Description

Biochem/physiol Actions

Potent, cell-permeable, IP3-independent intracellular calcium releaser. Blocks the transient increase in intracellular Ca2+ induced by angiostatin and endostatin. Induces apoptosis by disrupting intracellular free Ca2+ levels; incorporated into chemotherapeutic prodrug formulations.

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Safety & Documentation

Safety Information

Symbol 
Signal word 
Danger
Hazard statements 
Precautionary statements 
Personal Protective Equipment 
Hazard Codes (Europe) 
Xn
Risk Statements (Europe) 
Safety Statements (Europe) 
26-36/37/39
RIDADR 
UN 2811 6.1 / PGII
WGK Germany 
3

Protocols & Articles

Peer-Reviewed Papers

References

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Translational Repression Mediates Activation of Nuclear Factor Kappa B by Phosphorylated Translation Initiation Factor 2 Deng, J., et al. Mol. Cell. Biol. 24, 10161-8, (2004)

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A tool coming of age: thapsigargin as an inhibitor of sarco-endoplasmic reticulum Ca2+-ATPases. Treiman, M., et al. Trends Pharmacol. Sci. 19, 131-135, (1998)

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Distinct Autophagosomal-Lysosomal Fusion Mechanism Revealed by Thapsigargin-Induced Autophagy Arrest Ganley, I. G. et al. Mol. Cell. 42, 731-743, (2011)

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Mutant FUS Proteins That Cause Amyotrophic Lateral Sclerosis Incorporate Into Stress Granules. Bosco, D.A., et al. Hum. Mol. Genet. 19, 4160-75, (2010)

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The Calcium ATPase SERCA2 Regulates Desmoplakin Dynamics And Intercellular Adhesive Strength Through Modulation Of PKCα Signaling. Hobbs, R.P., et al. FASEB J. 25, 990-1001, (2011)

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Regulation of tissue inhibitor of metalloproteinases-1 in rat Sertoli cells: induction by germ cell residual bodies, interleukin-1alpha, and second messengers. Grønning LM, Wang JE, Ree AH, et al. Biol. Reprod. 62(4), 1040-6, (2000)

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Thapsigargin directly induces the mitochondrial permeability transition. Korge, P. and Weiss, J.N. Eur. J. Biochem. 265, 273-280, (1999)

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The Calpain, Caspase 12, Caspase 3 Cascade Leading To Apoptosis Is Altered In F508del-CFTR Expressing Cells. Kerbiriou, M., et al. PLoS ONE 4, e8436, (2009)

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Thapsigargin inhibits a potassium conductance and stimulates calcium influx in the intact rat lens. Thomas, G.R., et al. J. Physiol. London, England 516, 191-199, (1999)

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Calcium Flux Between The Endoplasmic Reticulum And Mitochondrion Contributes To Poliovirus-induced Apoptosis. Brisac, C., et al. J. Virol. 84, 12226-35, (2010)

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Acetylcholine Induces Ca2+ Signaling In Chicken Retinal Pigmented Epithelial Cells During Dedifferentiation. Sekiguchi-Tonosaki, M., et al. Am. J. Physiol. Cell Physiol. 296, C1195-206, (2009)

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Chemical genetics reveals a complex functional ground state of neural stem cells Diamandis, P., et. al. Nat. Chem. Biol. 3(5), 268-273, (2007)

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Spiroindolones, a potent compound class for the treatment of malaria. Matthias Rottmann et al Science 329, 1175-80, (2010)

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Role of Ca2(+)-ATPases in regulation of cellular Ca2+ signalling, as studied with the selective microsomal Ca2(+)-ATPase inhibitor, thapsigargin. Thastrup O Agents Actions 29(1-2), 8-15, (1990)

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Mechanism of antimalarial action of the synthetic trioxolane RBX11160 (OZ277). Anne-Catrin Uhlemann et al Antimicrob. Agents Chemother. 51, 667-72, (2007)

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Hsp90 inhibition by PU-H71 induces apoptosis through endoplasmic reticulum stress and mitochondrial pathway in cancer cells and overcomes the resistance conferred by Bcl-2. Gallerne C, Prola A, and Lemaire C Biochim. Biophys. Acta 1833(6), 1356-66, (2013)

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SERCA-inhibiting activity of C-19 terpenolides from Thapsia garganica and their possible biogenesis. Giovanni Appendino et al J. Nat. Prod. 68, 1213-7, (2005)

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Calcium signaling recruits substrate transporters GLUT4 and CD36 to the sarcolemma without increasing cardiac substrate uptake. Angin Y, Schwenk RW, Nergiz-Unal R, et al. Am. J. Physiol. Endocrinol. Metab. 307(2), E225-36, (2014)

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Applying linear interaction energy method for rational design of noncompetitive allosteric inhibitors of the sarco- and endoplasmic reticulum calcium-ATPase. Pratap Singh et al J. Med. Chem. 48, 3005-14, (2005)

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The Parkinson's disease-associated GPR37 receptor-mediated cytotoxicity is controlled by its intracellular cysteine-rich domain. Gandía J, Fernández-Dueñas V, Morató X, et al. J. Neurochem. 125(3), 362-72, (2013)

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Novel targets for Huntington's disease in an mTOR-independent autophagy pathway. Andrea Williams et al Nat. Chem. Biol. 4, 295-305, (2008)

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Total synthesis of two novel subpicomolar sarco/endoplasmatic reticulum Ca2+-ATPase inhibitors designed by an analysis of the binding site of thapsigargin. Helmer Søhoel et al J. Med. Chem. 48, 7005-11, (2005)

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In vitro interaction of artemisinin derivatives or the fully synthetic peroxidic anti-malarial OZ277 with thapsigargin in Plasmodium falciparum strains. Abiodun OO, Brun R, and Wittlin S Malaria Journal 12, 43, (2013)

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Thapsigargin: potent inhibitor of Ca2+ transport ATP-ases of endoplasmic and sarcoplasmic reticulum. Sabała P, Czarny M, Woronczak JP, et al. Acta Biochim. Pol. 40(3), 309-19, (1993)

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Activation of calcium-sensing receptor increases TRPC3/6 expression in T lymphocyte in sepsis. Wu QY, Sun MR, Wu CL, et al. Mol. Immunol. 64(1), 18-25, (2015)

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An endoplasmic reticulum stress-initiated sphingolipid metabolite, ceramide-1-phosphate, regulates epithelial innate immunity by stimulating β-defensin production. Kim YI, Park K, Kim JY, et al. Mol. Cell. Biol. 34(24), 4368-78, (2014)

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Waves of calcium depletion in the sarcoplasmic reticulum of vascular smooth muscle cells: an inside view of spatiotemporal Ca2+ regulation. Esfandiarei M, Fameli N, Choi YY, et al. PLoS ONE 8(2), e55333, (2013)

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Photoactivated fullerene C60 induces store-operated Ca2 entry and cytochrome c release in Jurkat cells. Grebinyk SM, Palyvoda KO, Prylutska SV, et al. Ukr. Biokhim. Zh. 84(6), 58-63, (2012)

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Polystyrene nanoparticles activate ion transport in human airway epithelial cells. McCarthy J, Gong X, Nahirney D, et al. Int. J. Nanomedicine 6, 1343-56, (2011)

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Water-mediated interactions influence the binding of thapsigargin to sarco/endoplasmic reticulum calcium adenosinetriphosphatase. Paulsen ES, Villadsen J, Tenori E, et al. J. Med. Chem. 56(9), 3609-19, (2013)

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Increased expression of endoplasmic reticulum stress and unfolded protein response genes in peripheral blood mononuclear cells from patients with limited cutaneous systemic sclerosis and pulmonary arterial hypertension. Lenna S, Farina AG, Martyanov V, et al. Arthritis Rheum. 65(5), 1357-66, (2013)

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Secreted bacterial effectors that inhibit host protein synthesis are critical for induction of the innate immune response to virulent Legionella pneumophila. Fontana MF, Banga S, Barry KC, et al. PLoS Pathog. 7(2), e1001289, (2011)

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Intracellular signaling in ER stress-induced autophagy in skeletal muscle cells. Madaro L, Marrocco V, Carnio S, et al. FASEB J. 27(5), 1990-2000, (2013)

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Complementary genomic screens identify SERCA as a therapeutic target in NOTCH1 mutated cancer. Roti G, Carlton A, Ross KN, et al. Cancer Cell 23(3), 390-405, (2013)

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STIM1-Orai1 interactions and Orai1 conformational changes revealed by live-cell FRET microscopy. Navarro-Borelly L J. Physiol. 586(Pt 22), 5383-401, (2008)

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An upstream open reading frame modulates ebola virus polymerase translation and virus replication. Shabman RS, Hoenen T, Groseth A, et al. PLoS Pathog. 9(1), e1003147, (2013)

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Small molecule regulators of autophagy identified by an image-based high-throughput screen. Lihong Zhang et al Proc. Natl. Acad. Sci. U. S. A. 104, 19023-8, (2007)

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SERCA2 dysfunction in Darier disease causes endoplasmic reticulum stress and impaired cell-to-cell adhesion strength: rescue by Miglustat. Savignac M, Simon M, Edir A, et al. J. Invest. Dermatol. 134(7), 1961-70, (2014)

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A monoclonal antibody TrkB receptor agonist as a potential therapeutic for Huntington's disease. Todd D, Gowers I, Dowler SJ, et al. PLoS ONE 9(2), e87923, (2014)

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Exendin-4 attenuates high glucose-induced cardiomyocyte apoptosis via inhibition of endoplasmic reticulum stress and activation of SERCA2a. Younce CW, Burmeister MA, and Ayala JE Am. J. Physiol. Cell Physiol. 304(6), C508-18, (2013)

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Artemisinins inhibit Trypanosoma cruzi and Trypanosoma brucei rhodesiense in vitro growth. Yuliya V Mishina et al Antimicrob. Agents Chemother. 51, 1852-4, (2007)

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Mild endoplasmic reticulum stress promotes retinal neovascularization via induction of BiP/GRP78. Nakamura S, Takizawa H, Shimazawa M, et al. PLoS ONE 8(3), e60517, (2013)

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Genetic mapping of targets mediating differential chemical phenotypes in Plasmodium falciparum. Jing Yuan et al Nat. Chem. Biol. 5, 765-71, (2009)

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Dose-dependent effects of angiotensin-(1-7) on the NHE3 exchanger and [Ca(2+)](i) in in vivo proximal tubules. Castelo-Branco RC, Leite-Delova DC, and de Mello-Aires M Am. J. Physiol. Renal Physiol. 304(10), F1258-65, (2013)

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Translation without eIF2 promoted by poliovirus 2A protease. Redondo N, Sanz MA, Welnowska E, et al. PLoS ONE 6(10), e25699, (2011)

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Epstein-barr virus blocks the autophagic flux and appropriates the autophagic machinery to enhance viral replication. Granato M, Santarelli R, Farina A, et al. J. Virol. 88(21), 12715-26, (2014)

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Design, synthesis, and development of novel guaianolide-endoperoxides as potential antimalarial agents. Lingzhi Sun et al J. Med. Chem. 53, 7864-8, (2010)

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Elucidation of the topography of the thapsigargin binding site in the sarco-endoplasmic calcium ATPase. Dorthe Mondrup Skytte et al Bioorg. Med. Chem. 18, 5634-46, (2010)

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pERp1 is significantly up-regulated during plasma cell differentiation and contributes to the oxidative folding of immunoglobulin. Shimizu Y Proc. Natl. Acad. Sci. U. S. A. 106(40), 17013-8, (2009)

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Endoplasmic reticulum stress in spinal and bulbar muscular atrophy: a potential target for therapy. Montague K, Malik B, Gray AL, et al. Brain 137(Pt 7), 1894-906, (2014)

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Characterization of novel store-operated calcium entry effectors. Djillani A, Nüße O, and Dellis O Biochim. Biophys. Acta 1843(10), 2341-7, (2014)

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The role of calcium in VDAC1 oligomerization and mitochondria-mediated apoptosis. Keinan N, Pahima H, Ben-Hail D, et al. Biochim. Biophys. Acta 1833(7), 1745-54, (2013)

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[6]-gingerol induces Ca2+ mobilization in Madin-Darby canine kidney cells. Chung-Yi Chen et al J. Nat. Prod. 71, 137-40, (2008)

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Artemisinin-resistant mutants of Toxoplasma gondii have altered calcium homeostasis. Kisaburo Nagamune et al Antimicrob. Agents Chemother. 51, 3816-23, (2007)

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Thapsigargin, a high affinity and global inhibitor of intracellular Ca2+ transport ATPases. Inesi G and Sagara Y Arch. Biochem. Biophys. 298(2), 313-7, (1992)

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The sarcoplasmic reticulum Ca2+ pump: inhibition by thapsigargin and enhancement by adenovirus-mediated gene transfer. Inesi G, Wade R, and Rogers T Ann. N. Y. Acad. Sci. 853, 195-206, (1998)

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Over-expression of X-linked inhibitor of apoptosis protein modulates multiple aspects of neuronal Ca2+ signaling. Grant J, Parker K, Moore CS, et al. Neurochem. Res. 38(4), 847-56, (2013)

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Chemical induction of the unfolded protein response in the liver increases glucose production and is activated during insulin-induced hypoglycaemia in rats. J. C. Gonzales et al Diabetologia 51, 1920-9, (2008)

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Carbon monoxide-releasing molecules reverse leptin resistance induced by endoplasmic reticulum stress. Zheng M, Zhang Q, Joe Y, et al. Am. J. Physiol. Endocrinol. Metab. 304(7), E780-8, (2013)

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Intercellular Ca(2+) wave propagation in human retinal pigment epithelium cells induced by mechanical stimulation. Abu Khamidakh AE, Juuti-Uusitalo K, Larsson K, et al. Exp. Eye Res. 108, 129-39, (2013)

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Deciliation is associated with dramatic remodeling of epithelial cell junctions and surface domains. Overgaard CE Mol. Biol. Cell 20(1), 102-13, (2009)

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The unfolded protein response selectively targets active smoothened mutants. Marada S, Stewart DP, Bodeen WJ, et al. Mol. Cell. Biol. 33(12), 2375-87, (2013)

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PCAF interacts with XBP-1S and mediates XBP-1S-dependent transcription. Qiao Jing Lew et al Nucleic Acids Res. 39, 429-39, (2011)

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ER stress responses in the absence of apoptosome: a comparative study in CASP9 proficient vs deficient mouse embryonic fibroblasts. Deegan S, Saveljeva S, Gupta S, et al. Biochem. Biophys. Res. Commun. 451(3), 367-73, (2014)

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Imaging of mitochondrial and non-mitochondrial responses in cultured rat hippocampal neurons exposed to micromolar concentrations of TMRM. Monteith A, Marszalec W, Chan P, et al. PLoS ONE 8(3), e58059, (2013)

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Taurine may not alleviate hyperglycemia-mediated endoplasmic reticulum stress in human adipocytes. Kim KS, Ji HI, and Yang HI Adv. Exp. Med. Biol. 775, 395-403, (2013)

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Use of thapsigargin to study Ca2+ homeostasis in cardiac cells. Rogers TB, Inesi G, Wade R, et al. Biosci. Rep. 15(5), 341-9, (1995)

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Serum deprivation can suppress receptor-mediated calcium signaling in pterygial-derived fibroblasts. Fang C, Illingworth CD, Qian L, et al. Invest. Ophthalmol. Vis. Sci. 54(7), 4563-70, (2013)

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Luman recruiting factor regulates endoplasmic reticulum stress in mouse ovarian granulosa cell apoptosis. Yang Y, Lin P, Chen F, et al. Theriogenology 79(4), 633-9.e1-3, (2013)

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Quinotrierixin inhibits proliferation of human retinal pigment epithelial cells. Chen C, Wang JJ, Li J, et al. Mol. Vis. 19, 39-46, (2013)

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N-Acetylcysteine increases corneal endothelial cell survival in a mouse model of Fuchs endothelial corneal dystrophy. Kim EC, Meng H, and Jun AS Exp. Eye Res. 127, 20-5, (2014)

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Role of caspase-3 cleaved IP3 R1 on Ca(2+) homeostasis and developmental competence of mouse oocytes and eggs. Zhang N and Fissore RA J. Cell Physiol. 229(11), 1842-54, (2014)

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Ca(2+)-mediated regulation of VDAC1 expression levels is associated with cell death induction. Weisthal S, Keinan N, Ben-Hail D, et al. Biochim. Biophys. Acta 1843(10), 2270-81, (2014)

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Thapsigargin blocks Pseudomonas aeruginosa homoserine lactone-induced apoptosis in airway epithelia. Schwarzer C, Ravishankar B, Patanwala M, et al. Am. J. Physiol. Cell Physiol. 306(9), C844-55, (2014)

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Neutrophil elastase induces MUC5AC secretion via protease-activated receptor 2. Zhou J, Perelman JM, Kolosov VP, et al. Mol. Cell Biochem. 377(1-2), 75-85, (2013)

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Store-operated calcium entry in vagal sensory nerves is independent of Orai channels. Hooper JS, Hadley SH, Mathews A, et al. Brain Res. 1503, 7-15, (2013)

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Chemical chaperones reduce ionizing radiation-induced endoplasmic reticulum stress and cell death in IEC-6 cells. Lee ES, Lee HJ, Lee YJ, et al. Biochem. Biophys. Res. Commun. 450(2), 1005-9, (2014)

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A sensitive assay for the biosynthesis and secretion of MANF using NanoLuc activity. Norisada J, Hirata Y, Amaya F, et al. Biochem. Biophys. Res. Commun. 449(4), 483-9, (2014)

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Modulation of calcium signalling by the endoplasmic reticulum in Carassius neurons. Lukyanets IA and Lukyanetz EA Biochem. Biophys. Res. Commun. 433(4), 591-4, (2013)

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Endoplasmic reticulum stress suppresses lipin-1 expression in 3T3-L1 adipocytes. Takahashi N, Yoshizaki T, Hiranaka N, et al. Biochem. Biophys. Res. Commun. 431(1), 25-30, (2013)

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Zinc deficiency induced in Swiss 3T3 cells by a low-zinc medium impairs calcium entry and two mechanisms of entry are involved. O'Dell BL and Browning JD Biol. Trace Elem. Res. 152(1), 98-104, (2013)

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