Rosiglitazone induces the unfolded protein response, but has no significant effect on cell viability, in monocytic and vascular smooth muscle cells

Biochemical and Biophysical Research Communications

Volumn 400, Issue 4, 2010, Pages 689-695

  Caddy, J ^a   Isa, S ^a   Mainwaring, L S ^a   Adam, E ^b   Roberts, A ^c   Lang, D ^c   Morris, R H K ^a   Thomas, A W ^a   Webb, R ^a  

^a CARDIFF METROPOLITAN UNIVERSITY   (United Kingdom)

^b Hogeschool West Vlaanderen   (Belgium)

^c CARDIFF UNIVERSITY   (United Kingdom)

Author keywords

ER stress; Monocytes; Rosiglitazone; SERCA2b; Type 2 diabetes; Unfolded protein response; VSMCs

Indexed keywords

ADENOSINE TRIPHOSPHATASE; CALCIUM ION; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; ROSIGLITAZONE; X BOX BINDING PROTEIN 1;

APOPTOSIS; ARTICLE; CALCIUM DEPLETION; CELL VIABILITY; CONTROLLED STUDY; DRUG EFFECT; ENZYME ACTIVITY; FLUOROMETRY; HUMAN; HUMAN CELL; IC 50; PRIORITY JOURNAL; PROTEIN EXPRESSION; RECEPTOR UPREGULATION; SMOOTH MUSCLE FIBER;

CALCIUM; CELL LINE; CELL SURVIVAL; DNA-BINDING PROTEINS; GENE EXPRESSION; HEAT-SHOCK PROTEINS; HOMEOSTASIS; HUMANS; HYPOGLYCEMIC AGENTS; MONOCYTES; MUSCLE, SMOOTH, VASCULAR; MYOCYTES, SMOOTH MUSCLE; SARCOPLASMIC RETICULUM CALCIUM-TRANSPORTING ATPASES; THIAZOLIDINEDIONES; TRANSCRIPTION FACTORS; UNFOLDED PROTEIN RESPONSE; VASODILATOR AGENTS;

EID: 77957285055     PISSN: 0006291X     EISSN: 10902104     Source Type: Journal    
DOI: 10.1016/j.bbrc.2010.08.129     Document Type: Article

References (38)

1. Smith S.A. Central role of the adipocyte in the insulin-sensitizing and cardiovascular risk modifying actions of the thiazolidinediones. Biochimie 2003, 85:1219-1230.
2. Hetzel J., Balletshoffer B., Rittig K., et al. Rapid effects of Rosiglitazone treatment on endothelial function and inflammatory biomarkers. Arterioscler. Thromb. Vacs. Biol. 2005, 25:1804-1809.
3. Singh N., Webb R., Adams R., et al. The PPAR-γ activator, Rosiglitazone, inhibits actin polymerisation in monocytes: involvement of Akt and intracellular calcium. Biochem. Biophys. Res. Commun. 2005, 333:455-462.
4. Caddy J., Singh N., Atkin L., et al. Rosiglitazone transiently disturbs calcium homeostasis in monocytic cells. Biochem. Biophys. Res. Commun. 2008, 366:149-155.
5. Nissen S.E., Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N. Engl. J. Med. 2007, 356:2457-2471.
6. Juurlink D.N., Gomes T., Lipscombe L.L., Austin P.C., Hux J.E., Mamdani M.M. Adverse cardiovascular events during treatment with pioglitazone and rosiglitazone: population based cohort study. BMJ 2009, 339:b2942.
7. Home P.D., Pocock S.J., Beck-Nielsen H., et al. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet 2009, 373(9681):2125-2135.
8. C.J. Rosen, Revisiting the Rosiglitazone story - lessons learned, New Engl. J. Med. (2010) [epub ahead of print].
9. Szegezdi E., Duffy A., O'Mahoney M.E., et al. ER stress contributes to ischemia-induced cardiomyocyte apoptosis. Biochem. Biophys. Res. Commun. 2001, 349(4):1406-1411.
10. Shah R.D., Gonzales F., Golez E., et al. The antidiabetic agent Rosiglitazone upregulates SERCA2 and enhances TNF-α- and LPS-induced NF-κβ-dependent transcription and Tnf-α-induced il-6 secretion in ventricular myocytes. Cell. Physiol. Biochem. 2004, 15:41-50.
11. 2+Atpase and μ-calpain activity are altered in type 2 diabetes and restored by rosiglitazone. Circulation 2008, 117:52-60.
12. Xu C., Baily-Maitre B., Reed J.C. Endoplasmic reticulum stress: cell life and death decisions. J. Clin. Invest. 2005, 115:2656-2664.
13. Sidrauski C., Chapman R., Walter P. The unfolded protein response: an intracellular signalling pathway with many surprising features. Trends Cell Biol. 1998, 8:245-249.
14. Endo M., Mori M., Akira S., Gotoh T. C/EBP homologous protein (CHOP) is crucial for the induction of caspase-11 and the pathogenesis of lipopolysaccharide-induced inflammation. J. Immunol. 2006, 176(10):6245-6253.
15. Yoshida H., Haze K., Yanagi H., Yura T., Mori K. Identification of the cis-acting endoplasmic reticulum stress response element responsible for transcriptional induction of mammalian glucose-regulated proteins. Involvement of basic leucine zipper transcription factors. J. Biol. Chem. 1998, 273(50):33741-33749.
16. Thuerauf D.J., Hoover H., Meller J., et al. Sarco/endoplasmic reticulum calcium ATPase-2 expression is regulated by ATF6 during the endoplasmic reticulum stress response: intracellular signaling of calcium stress in a cardiac myocyte model system. J. Biol. Chem. 2001, 276(51):48309-48317.
17. Ziegler-Heitbrock H.W., Thiel E., Fütterer A., Herzog V., Wirtz A., Riethmüller G. Establishment of a human cell line (Mono Mac 6) with characteristics of mature monocytes. Int. J. Cancer 1988, 41:456-461.
18. Kimes B.W., Brandt B.L. Characterization of two putative smooth muscle cell lines from rat thoracic aorta. Exp. Cell Res. 1976, 98(2):349-366.
19. Maruyama K., MacLennan D.H. Mutation of aspartic acid-351, lysine-352, and lysine-515 alters the Ca2+ activity of the Ca2+-ATPase expressed in COS-1 cells. Proc. Natl. Acad. Sci. 1988, 85:3314-3318.
20. 2+ pump isoforms in human cells. Biochem. J. 1992, 288:297-302.
21. 2+-ATPase of sarcoplasmic reticulum. J. Biol. Chem. 2000, 275:977-982.
22. 2- and other ions in solution, calculation of the true concentrations of species present in mixtures of associating ions. Biochem. J. 1976, 159:1-5.
23. Elsner J., Norgauer J., Dobos G.J., et al. Flow cytometry reveals different lag times in rapid cytoplasmic calcium elevations in human neutrophils in response to N-formyl peptide. J. Cell. Physiol. 1993, 157:637-643.
24. Shang J. Quantitative measurement of events in the mammalian unfolded protein response. Methods 2005, 35:390-394.
25. Kubisch C.H., Sans M.D., Arumugam T., Ernst S.A., Williams J.A., Logsdon C.D. Early activation of endoplasmic reticulum stress is associated with arginine-induced acute pancreatitus. Am. J. Physiol. Gastrointest. Liver Physiol. 2006, 291:G238-G245.
26. Marx N., Froehlich J., Siam L., et al. Antidiabetic PPARγ activator rosiglitazone reduces MMP-9 serum levels in type 2 diabetic patients with coronary artery disease. Arterioscler. Thromb. Vasc. Biol. 2003, 23:283-288.
27. Thastrup O., Cullen P.J., Drøbak B.K., Hanley M.R., Dawson A.P. Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2(+)-ATPase. Proc. Natl. Acad. Sci. USA 1990, 87(7):2466-2470.
28. Eckstein-Ludwig U., Webb R., van Goethem I.D., et al. Artemisins target the SERCA of Plasmodium falciparum. Nature 2003, 424:957-961.
29. Niemi M., Backman J.T., Granfors M., Laitila J., Neuvonen M., Neuvonen P.J. Gemfibrozil considerably increases the plasma concentrations of rosiglitazone. Diabetologia 2003, 46:1319-1323.
30. Afroze T., Yang L.L., Wang C., et al. Calcineurin-independent regulation of plasma membrane Ca2+ ATPase-4 in the vascular smooth muscle cell cycle. Am. J. Physiol. Cell Physiol. 2003, 285(1):C88-C95.
31. Scully S.P., Segel G.B., Lichtman M.A. Plasma membrane vesicles prepared from unadhered monocytes: characterization of calcium transport and the calcium ATPase. Cell Calcium 1982, 3(6):515-530.
32. Plutzky J. The potential role of PPARs on inflammation in type 2 diabetes and atherosclerosis. Am. J. Cardiol. 2003, 92:34-41.
33. Khanolkar M.P., Morris K., Thomas A.W., et al. Rosiglitazone produces a greater reduction in circulating platelet activity compared with gliclazide in patients with type 2 diabetes mellitus - an effect probably mediated by direct platelet PPARgamma activation. Atherosclerosis 2008, 197(2):718-724.
34. Gerstein H.C., Yusuf S., Bosch J., et al. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet 2006, 368:1096-1105. DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) Trial Investigators.
35. Murphy G.J., Holder J.C. PPAR-gamma agonists: therapeutic role in diabetes, inflammation and cancer. TiPS 2000, 21(12):469-474.
36. Takahashi S., Odani N., Tomokiyo K., et al. Localization of a cyclo-pentenone prostaglandin to the endoplasmic reticulum and induction of BiP mRNA. Biochem. J. 1998, 335:35-42.
37. Baldwin S.J., Clarke S.E., Chenery R.J. Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of rosiglitazone. Br. J. Clin. Pharmacol. 1999, 48(3):424-432.
38. GlaxoSmithKline fact sheet - Avandia 4mg and 8mg film-coated tablets, Revised edition (2009). Available from <>, 2010 (accessed 09.08.10. http://emc.medicines.org.uk.