title: Proteomic analysis of the differences in orbital protein expression in thyroid orbitopathy.
abstract: BACKGROUND
  Thyroid orbitopathy (TO) is a multi-system inflammatory disease characterized by orbital congestion, ocular surface disorders, restrictive myopathy, and skin lesions. The molecular and cellular processes of pathogenic formation of TO orbital fat tissues are not fully understood. In this study, a comparative proteomic analysis was conducted to investigate the importance of some differential proteins of orbital fat tissues in TO.
  
  
  METHODS
  The differential proteins were analyzed by comparing the two-dimensional gel electrophoresis (2-DE) maps of the orbital fat tissues of TO with those of normal orbital fat tissues. The 2-DE results were further verified by Western blot and immunohistochemistry.
  
  
  RESULTS
  Fifteen up-regulated and two down-regulated proteins in TO orbital fat tissues in comparison with the control were exhibited by 2-DE maps. The over-expressed proteins including guanine nucleotide-binding protein, isocitrate dehydrogenase (IDH), annexin A2, heat shock protein 60 (HSP 60), calreticulin (CALR), protein disulfide-isomerase A3 (PDIA3), spectrin, superoxide dismutase (SOD), and transitional endoplasmic reticulum ATPase (TER ATPase) may contribute to increased thyroid-stimulating hormone receptor (TSHR) expression and cell proliferation. The proteomic data of specific proteins are consistent with those determined by Western blot and immunohistochemistry.
  
  
  CONCLUSIONS
  Comparison of orbital fat proteins from thyroid orbitopathy with age-matched controls shows significant differences in the proteome, and up-regulations of the specific proteins in orbital fat tissues from TO are associated with biochemical mechanisms or capacities against endoplasmic reticulum stress, mitochondria dysfunction, and cell proliferation as well as apoptosis in TO orbital fat tissues.
authors: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Kai-Chun
authors: KC
authors: Cheng
authors: Han-Hsiang
authors: HH
authors: Huang
authors: Chun-Tzu
authors: CT
authors: Hung
authors: Cheng-Chi
authors: CC
authors: Chen
authors: Wen-Chuan
authors: WC
authors: Wu
authors: Jau-Ling
authors: JL
authors: Suen
authors: Kuo-Jen
authors: KJ
authors: Chen
authors: Yu-Jen
authors: YJ
authors: Wu
authors: Cheng-Hsien
authors: CH
authors: Chang
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D015180:Electrophoresis, Gel, Two-Dimensional; D005136:Eye Proteins / Q000378:metabolism*; D005260:Female; D049970:Graves Ophthalmopathy / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009915:Orbit; D009916:Orbital Diseases / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D053719:Tandem Mass Spectrometry; D015854:Up-Regulation
chemical_list: D005136:Eye Proteins
references: Cancer Metastasis Rev. 2009 Jun;28(1-2):219-23
references: 19172382
references: Br J Ophthalmol. 1996 Oct;80(10):922-6
references: 8976707
references: Mol Cell Biol. 1988 Jan;8(1):1-9
references: 3336352
references: Endocrinology. 2005 Jan;146(1):477-85
references: 15498884
references: Electrophoresis. 2012 Apr;33(7):1139-52
references: 22539317
references: Trends Biochem Sci. 1994 Jan;19(1):20-5
references: 7908149
references: Curr Eye Res. 2008 May;33(5):421-7
references: 18568878
references: Clin Exp Immunol. 1989 Feb;75(2):222-7
references: 2784734
references: Eur J Endocrinol. 2005 May;152(5):777-84
references: 15879364
references: J Clin Endocrinol Metab. 1997 Jun;82(6):2003-5
references: 9177421
references: Clin Pharmacol Ther. 2012 Apr;91(4):577-9
references: 22434030
references: Semin Cell Biol. 1990 Feb;1(1):65-72
references: 1983272
references: Thyroid. 1999 Mar;9(3):289-95
references: 10211607
references: Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3280-5
references: 18296637
references: J Mol Endocrinol. 2011 Apr 12;46(3):155-63
references: 21321093
references: Anticancer Agents Med Chem. 2008 Jan;8(1):22-36
references: 18220503
references: J Cell Biol. 2004 Jan 5;164(1):35-46
references: 14699087
references: Horm Metab Res. 1993 Dec;25(12):618-22
references: 8119665
references: Clin Endocrinol (Oxf). 2005 Jan;62(1):24-9
references: 15638866
references: J Biol Chem. 2008 Feb 22;283(8):5188-94
references: 18086682
references: J Biol Chem. 2009 Jan 23;284(4):2409-18
references: 18978357
references: Proteomics. 2006 Nov;6(22):5898-902
references: 17051642
references: Immunol Res. 2012 Dec;54(1-3):191-203
references: 22434518
references: Proc Natl Acad Sci U S A. 2011 Apr 19;108(16):6561-6
references: 21464300
references: J Biol Chem. 1998 Nov 6;273(45):29615-25
references: 9792671
references: N Engl J Med. 1993 Nov 11;329(20):1468-75
references: 8413459
references: Nat Cell Biol. 2001 Dec;3(12):1086-91
references: 11781570
references: Mt Sinai J Med. 2004 Oct;71(5):289-97
references: 15543429
references: Clin Exp Immunol. 2005 Apr;140(1):166-72
references: 15762888
references: Lancet. 1991 Jul 6;338(8758):25-8
references: 1676091
references: Int J Inflam. 2011;2011:259462
references: 21755026
references: Endocrinology. 2010 Nov;151(11):5537-49
references: 20844004
references: J Thyroid Res. 2012;2012:302537
references: 22175033
references: Endocr Rev. 2003 Dec;24(6):802-35
references: 14671007
references: Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):507-12
references: 11149950
references: J Clin Endocrinol Metab. 1999 Jul;84(7):2557-62
references: 10404836
references: Endocr Pract. 1998 May-Jun;4(3):127-32
references: 15251739
references: Infect Immun. 2009 Apr;77(4):1357-67
references: 19179416
references: J Clin Endocrinol Metab. 1998 Mar;83(3):998-1002
references: 9506762
references: J Clin Endocrinol Metab. 2011 Dec;96(12):3827-37
references: 21956421
references: Mol Biol Cell. 2010 Sep 15;21(18):3093-105
references: 20660153
references: Mod Pathol. 1998 Feb;11(2):155-68
references: 9504686