#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Mitochondrial dysfunction in rheumatoid arthritis: A comprehensive analysis by integrating gene expression, protein-protein interactions and gene ontology data


Autoři: Venugopal Panga aff001;  Ashwin Adrian Kallor aff001;  Arunima Nair aff001;  Shilpa Harshan aff001;  Srivatsan Raghunathan aff001
Působiště autorů: Institute of Bioinformatics and Applied Biotechnology (IBAB), Bengaluru, Karnataka, India aff001;  Manipal Academy of Higher Education, Manipal, Karnataka, India aff002
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0224632

Souhrn

Several studies have reported mitochondrial dysfunction in rheumatoid arthritis (RA). Many nuclear DNA (nDNA) encoded proteins translocate to mitochondria, but their participation in the dysfunction of this cell organelle during RA is quite unclear. In this study, we have carried out an integrative analysis of gene expression, protein-protein interactions (PPI) and gene ontology data. The analysis has identified potential implications of the nDNA encoded proteins in RA mitochondrial dysfunction. Firstly, by analysing six synovial microarray datasets of RA patients and healthy controls obtained from the gene expression omnibus (GEO) database, we found differentially expressed nDNA genes that encode mitochondrial proteins. We uncovered some of the roles of these genes in RA mitochondrial dysfunction using literature search and gene ontology analysis. Secondly, by employing gene co-expression from microarrays and collating reliable PPI from seven databases, we created the first mitochondrial PPI network that is specific to the RA synovial joint tissue. Further, we identified hubs of this network, and moreover, by integrating gene expression and network analysis, we found differentially expressed neighbours of the hub proteins. The results demonstrate that nDNA encoded proteins are (i) crucial for the elevation of mitochondrial reactive oxygen species (ROS) and (ii) involved in membrane potential, transport processes, metabolism and intrinsic apoptosis during RA. Additionally, we proposed a model relating to mitochondrial dysfunction and inflammation in the disease. Our analysis presents a novel perspective on the roles of nDNA encoded proteins in mitochondrial dysfunction, especially in apoptosis, oxidative stress-related processes and their relation to inflammation in RA. These findings provide a plethora of information for further research.

Klíčová slova:

Apoptosis – Gene expression – Gene ontologies – Genetic networks – Inflammation – Microarrays – Mitochondria – Protein interaction networks


Zdroje

1. Fearon U, Canavan M, Biniecka M, Veale DJ. Hypoxia, mitochondrial dysfunction and synovial invasiveness in rheumatoid arthritis. Nat Rev Rheumatol. 2016; 12: 385–97. doi: 10.1038/nrrheum.2016.69 27225300

2. Medina-Gomez G. Mitochondrial and endocrine function of adipose tissue. Best Pract Res Clin Endocrinol Metab. 2012; 26: 791–804. doi: 10.1016/j.beem.2012.06.002 23168280

3. Pagano G, Castello G, Pallardó FV. Sjøgren’s syndrome-associated oxidative stress and mitochondrial dysfunction: prospects for chemoprevention trials. Free Radic Res. 2013; 47: 71–3. doi: 10.3109/10715762.2012.748904 23153390

4. Ouang J, Wu M, Huang C, Cao L, Li G. Overexpression of oxidored-nitro domain containing protein 1 inhibits human nasopharyngeal carcinoma and cervical cancer cell proliferation and induces apoptosis: Involvement of mitochondrial apoptotic pathways. Oncol Rep. 2013; 29: 79–86. doi: 10.3892/or.2012.2101 23124592

5. Osellame LD, Blacker TS, Duchen MR. Cellular and molecular mechanisms of mitochondrial function. Best Pract Res Clin Endocrinol Metab. 2012; 26: 711–23. doi: 10.1016/j.beem.2012.05.003 23168274

6. Legault JT, Strittmatter L, Tardif J, Sharma R, Tremblay-Vaillancourt V, Aubut C, et al. A metabolic signature of mitochondrial dysfunction revealed through a monogenic form of Leigh syndrome. Cell Rep. 2015; 13(5): 981–89. doi: 10.1016/j.celrep.2015.09.054 26565911

7. Bick AG, Wakimoto H, Kamer KJ, Sancak Y, Goldberger O, Axelsson A, et al. Cardiovascular homeostasis dependence on MICU2, a regulatory subunit of the mitochondrial calcium uniporter. Proc Natl Acad Sci. 2017; 114(43): e9096–9104. doi: 10.1073/pnas.1711303114 29073106

8. Lake NJ, Webb BD, Stroud DA, Richman TR, Ruzzenente B, Compton AG, et al. Biallelic mutations in MRPS34 lead to instability of the small mitoribosomal subunit and Leigh syndrome. Am J Hum Genet. 2017; 101(2): 239–54. doi: 10.1016/j.ajhg.2017.07.005 28777931

9. Dai N, Zhao L, Wrighting D, Krämer D, Majithia A, Wang Y, et al. IGF2BP2/IMP2-deficient mice resist obesity through enhanced translation of Ucp1 mRNA and other mRNAs encoding mitochondrial proteins. Cell Metab. 2015; 21(4): 609–21. doi: 10.1016/j.cmet.2015.03.006 25863250

10. Tucker EJ, Hershman SG, Kohrer C, Belcher-Timme CA, Patel J, Goldberger OA, et al. Mutations in MTFMT underlie a human disorder of formylation causing impaired mitochondrial translation. Cell Metab. 2011; 14(3): 428–34. doi: 10.1016/j.cmet.2011.07.010 21907147

11. Fassone E, Duncan AJ, Taanman JW, Pagnamenta AT, Sadowski MI, Holand T, et al. FOXRED1, encoding an FAD-dependent oxidoreductase complex-I-specific molecular chaperone, is mutated in infantile-onset mitochondrial encephalopathy. Hum Mol Genet. 2010; 19(24): 4837–47. doi: 10.1093/hmg/ddq414 20858599

12. Gohil VM, Nilsson R, Belcher-Timme CA, Luo B, Root DE, Mootha VK. Mitochondrial and nuclear genomic responses to loss of LRPPRC expression. J Biol Chem. 2010; 285(18): 13742–7. doi: 10.1074/jbc.M109.098400 20220140

13. Kamer KJ, Mootha VK. MICU1 and MICU2 play nonredundant roles in the regulation of the mitochondrial calcium uniporter. EMBO Rep. 2014; 15(3): 299–07. doi: 10.1002/embr.201337946 24503055

14. Sancak Y, Markhard AL, Kitami T, Kovács-Bogdán E, Kamer KJ, Udeshi ND, et al. EMRE is an essential component of the mitochondrial calcium uniporter complex. Science. 2013; 342(6164): 1379–82. doi: 10.1126/science.1242993 24231807

15. Plovanich M, Bogorad RL, Sancak Y, Kamer KJ, Strittmatter L, Li AA, et al. MICU2, a paralog of MICU1, resides within the mitochondrial uniporter complex to regulate calcium handling. Plos One. 2013; 8(2): e55785. doi: 10.1371/journal.pone.0055785 23409044

16. Calvo SE, Clauser KR, Mootha VK. MitoCarta2.0: an updated inventory of mammalian mitochondrial proteins. Nucleic Acids Res. 2016; 44: D1251–7. doi: 10.1093/nar/gkv1003 26450961

17. McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol. 2007; 7(6): 429–42. doi: 10.1038/nri2094 17525752

18. Moelants EA, Mortier A, Van Damme J, Proost P. Regulation of TNF-alpha with a focus on rheumatoid arthritis. Immunol Cell Biol. 2013; 91: 393–401. doi: 10.1038/icb.2013.15 23628802

19. Smith MD. The normal synovium. Open Rheumatol J. 2011; 5: 100–06. doi: 10.2174/1874312901105010100 22279508

20. Bromley M, Woolley DE. Histopathology of the rheumatoid lesion. Identification of cell types at sites of cartilage erosion. Arthritis Rheum. 1984; 27(8): 857–63. doi: 10.1002/art.1780270804 6466394

21. Tak PP, Bresnihan B. The pathogenesis and prevention of joint damage in rheumatoid arthritis: advances from synovial biopsy and tissue analysis. Arthritis Rheum. 2000; 43(12): 2619–33. doi: 10.1002/1529-0131(200012)43:12<2619::AID-ANR1>3.0.CO;2-V 11145019

22. Ng CT, Biniecka M, Kennedy A, McCormick J, FitzGerald O, Bresnihan B, et al. Synovial tissue hypoxia and inflammation in vivo. Ann Rheum Dis. 2010; 69(7): 1389–95. doi: 10.1136/ard.2009.119776 20439288

23. Hildeman DA, Mitchell T, Kappler J, Marrack P. T cell apoptosis and reactive oxygen species. J Clin Invest. 2003; 111: 575–81. doi: 10.1172/JCI18007 12618509

24. Kennedy A, Ng CT, Chang TC, Biniecka M, O’Sullivan JN, Heffernan E, et al. Tumor necrosis factor blocking therapy alters joint inflammation and hypoxia. Arthritis Rheum. 2011; 63(4): 923–32. doi: 10.1002/art.30221 21225682

25. Hitchon CA, El-Gabalawy HS. Oxidation in rheumatoid arthritis. Arthritis Res Ther. 2004; 6: 265–78. doi: 10.1186/ar1447 15535839

26. Madamanchi NR, Runge MS. Mitochondrial dysfunction in atherosclerosis. Circ Res. 2007; 100: 460–73. doi: 10.1161/01.RES.0000258450.44413.96 17332437

27. Kokoszka JE, Coskun P, Esposito LA, Wallace DC. Increased mitochondrial oxidative stress in the Sod2 (+/-) mouse results in the age-related decline of mitochondrial function culminating in increased apoptosis. Proc Natl Acad Sci. 2001; 98(5): 2278–83. doi: 10.1073/pnas.051627098 11226230

28. Hajizadeh S, DeGroot J, TeKoppele JM, Tarkowski A, Collins LV. Extracellular mitochondrial DNA and oxidatively damaged DNA in synovial fluid of patients with rheumatoid arthritis. Arthritis Res Ther. 2003; 5: R234–40. doi: 10.1186/ar787 12932286

29. Bashir S, Harris G, Denman MA, Blake DR, Winyard PG. Oxidative DNA damage and cellular sensitivity to oxidative stress in human autoimmune diseases. Ann Rheum Dis. 1993; 52: 659–66. doi: 10.1136/ard.52.9.659 8239761

30. Lemarechal H, Allanore Y, Chenevier-Gobeaux C, Kahan A, Ekindjian OG, Borderie D, et al. Serum protein oxidation in patients with rheumatoid arthritis and effects of infliximab therapy. Clin Chim Acta. 2006; 372: 147–53. doi: 10.1016/j.cca.2006.04.002 16716286

31. Dabbagh AJ, Trenam CW, Morris CJ, Blake DR. Iron in joint inflammation. Ann Rheum Dis. 1993; 52: 67–73. doi: 10.1136/ard.52.1.67 8427520

32. Dai L, Lamb DJ, Leake DS, Kus ML, Jones HW, Morris CJ, et al. Evidence for oxidized low density lipoprotein in synovial fluid from rheumatoid arthritis patients. Free Radic Res. 2000; 32: 479–86. doi: 10.1080/10715760000300481 10798713

33. Rowley D, Gutteridge JM, Blake D, Farr M, Halliwell B. Lipid peroxidation in rheumatoid arthritis: thiobarbituric acid-reactive material and catalytic iron salts in synovial fluid from rheumatoid patients. Clin Sci (Lond). 1984; 66(6): 691–5.

34. Grootveld M, Henderson EB, Farrell A, Blake DR, Parkes HG, Haycock P. Oxidative damage to hyaluronate and glucose in synovial fluid during exercise of the inflamed rheumatoid joint. Detection of abnormal low-molecular-mass metabolites by proton-n.m.r. spectroscopy. Biochem J. 1991; 273: 459–67. doi: 10.1042/bj2730459 1991041

35. Henrotin YE, Bruckner P, Pujol JPL. The role of reactive oxygen species in homeostasis and degradation of cartilage. Osteoarthritis and Cartilage. 2003; 11: 747–55. 13129694

36. Ushio-Fukai M, Tang Y, Fukai T, Dikalov SI, Ma Y, Fujimoto M, et al. Novel role of gp91phox-containing NAD(P)H oxidase in vascular endothelial growth factor-induced signaling and angiogenesis. Circ Res. 2002; 91: 1160–67. doi: 10.1161/01.res.0000046227.65158.f8 12480817

37. Cerhan JR, Saag KG, Merlino LA, Mikuls TR, Criswell LA. Antioxidant micronutrients and risk of rheumatoid arthritis in a cohort of older women. Am J Epidemol. 2003; 157: 345–54.

38. Heliövaara M, Knekt P, Aho K, Aaran R-K, Alfthan G, Aromaa A. Serum antioxidants and risk of rheumatoid arthritis. Ann Rheum Dis. 1994; 53(1): 51–53. doi: 10.1136/ard.53.1.51 8311556

39. Hagfors L, Leanderson P, Skoldstam L, Andersson J, Johansson G. Antioxidant intake, plasma antioxidants and oxidative stress in a randomized, controlled, parallel, Mediterranean dietary intervention study on patients with rheumatoid arthritis. Nutr J. 2003; 2: 5. doi: 10.1186/1475-2891-2-5 12952549

40. Bae SC, Kim SJ, Sung MK. Inadequate antioxidant nutrient intake and altered plasma antioxidant status of rheumatoid arthritis patients. J Am Coll Nutr. 2003; 22(4): 311–5. doi: 10.1080/07315724.2003.10719309 12897046

41. Paredes S, Girona J, Hurt-Camejo E, Vallvé JC, Olivé S, Heras M, et al. Antioxidant vitamins and lipid peroxidation in patients with rheumatoid arthritis: association with inflammatory markers. J Rheumatol. 2002; 29(11): 2271–7. 12415581

42. Mulherin DM, Thurnham DI, Situnayake RD. Glutathione reductase activity, riboflavin status, and disease activity in rheumatoid arthritis. Ann Rheum Dis. 1996; 55: 837–914. doi: 10.1136/ard.55.11.837 8976642

43. Filippin LI, Vercelino R, Marroni NP, Xavier RM. Redox signalling and the inflammatory response in rheumatoid arthritis. Clin Exp Immunol. 2008; 152(3): 415–22. doi: 10.1111/j.1365-2249.2008.03634.x 18422737

44. Li H, Wan A. Apoptosis of rheumatoid arthritis fibroblast-like synoviocytes: possible roles of nitric oxide and the thioredoxin 1. Mediators Inflamm. 2013; 2013(3): 953462.

45. Palao G, Santiago B, Galindo M, Rullas J, Alcamí J, Ramirez JC, et al. Fas activation of a proinflammatory program in rheumatoid synoviocytes and its regulation by FLIP and caspase 8 signaling. Arthritis Rheum. 2006; 54(5): 1473–81. doi: 10.1002/art.21768 16646028

46. Chatr-Aryamontri A, Breitkreutz B-J, Oughtred R, Boucher L, Heinicke S, Chen D, et al. The BioGRID interaction database: 2015 update. Nucleic Acids Res. 2015; 43: D470–8. doi: 10.1093/nar/gku1204 25428363

47. Orchard S, Ammari M, Aranda B, Breuza L, Briganti L, Broackes-Carter F, et al. The MIntAct project—IntAct as a common curation platform for 11 molecular interaction databases. Nucleic Acids Res. 2014; 42: D358–63. doi: 10.1093/nar/gkt1115 24234451

48. Chatr-Aryamontri A, Ceol A, Palazzi LM, Nardelli G, Schneider MV, Castagnoli L, et al. MINT: the molecular interaction database. Nucleic Acids Res. 2007; 35: D572–74. doi: 10.1093/nar/gkl950 17135203

49. Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J, et al. STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 2015; 43(D1): D447–52.

50. Prasad TSK, Goel R, Kandasamy K, Keerthikumar S, Kumar S, Mathivanan S, et al. Human protein reference database—2009 update. Nucleic Acids Res. 2009; 37: D767–72. doi: 10.1093/nar/gkn892 18988627

51. Salwinski L, Miller CS, Smith AJ, Pettit FK, Bowie JU, Eisenberg D. The database of interacting proteins: 2004 update. Nucleic Acids Res. 2004; 32: D449–51. doi: 10.1093/nar/gkh086 14681454

52. Bossi A, Lehner B. Tissue specificity and the human protein interaction network. Mol Syst Biol. 2009; 5: 260. doi: 10.1038/msb.2009.17 19357639

53. Huber R, Hummert C, Gausmann U, Pohlers D, Koczan D, Guthke R, et al. Identification of intra-group, inter-individual, and gene-specific variances in mRNA expression profiles in the rheumatoid arthritis synovial membrane. Arthritis Res Ther. 2008; 10(14): R98.

54. Woetzel D, Huber R, Kupfer P, Pohlers D, Pfaff M, Driesch D, et al. Identification of rheumatoid arthritis and osteoarthritis patients by transcriptome-based rule set generation. Arthritis Res Ther. 2014; 16: R84. doi: 10.1186/ar4526 24690414

55. Franceschini A, Szklarczyk D, Frankild S, Kuhn M, Simonovic M, Roth A, et al. STRING v9.1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res. 2013; 41: D808–15. doi: 10.1093/nar/gks1094 23203871

56. Rivals I, Personnaz L, Taing L, Marie-Claude P. Enrichment or depletion of a GO category within a class of genes: which test? Bioinformatics. 2007; 23(4): 401–07. doi: 10.1093/bioinformatics/btl633 17182697

57. Dantzer R, O’Connor JC, Lawson MA, Kelley KW. Inflammation-associated depression: from serotonin to kynurenine. Psychoneuroendocrinology. 2011; 36(3): 426–36. doi: 10.1016/j.psyneuen.2010.09.012 21041030

58. Kaur H, Ganguli D, Bachhawat AK. Glutathione degradation by the alternative pathway (DUG pathway) in Saccharomyces cerevisiae is initiated by (Dug2p-Dug3p)2 complex, a novel glutamine amidotransferase (GATase) enzyme acting on glutathione. J Biol Chem. 2012; 287(12): 8920–31. doi: 10.1074/jbc.M111.327411 22277648

59. Kim JW, Tchernyshyov I, Semenza GL, Dang CV. HIF-1-mediated expression of pyruvate dehydrogenase kinase: A metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 2006; 3(3): 177–85. doi: 10.1016/j.cmet.2006.02.002 16517405

60. Rosebeck S, Leaman DW. Mitochondrial localization and pro-apoptotic effects of the interferon-inducible protein ISG12a. Apoptosis. 2008; 13(4): 562–72. doi: 10.1007/s10495-008-0190-0 18330707

61. Arsenijevic D, Onuma H, Pecqueur C, Raimbault S, Manning BS, Miroux B, et al. Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production. Nat Genet. 2000; 26(4): 435–9. doi: 10.1038/82565 11101840

62. Jin DY, Chae HZ, Rhee SG, Jeang KT. Regulatory role for a novel human thioredoxin peroxidise in NF-kappaB activation. J Biol Chem. 1997; 272(49): 30952–61. doi: 10.1074/jbc.272.49.30952 9388242

63. Wang X, Wang L, Wang X, Sun F, Wang CC. Structural insights into the peroxidase activity and inactivation of human peroxiredoxin 4. Biochem J. 2012; 441(1): 113–8. doi: 10.1042/BJ20110380 21916849

64. Hartmann B, Wai T, Hu H, MacVicar T, Musante L, Fischer-Zirnsak B, et al. Homozygous YME1L1 mutation causes mitochondriopathy with optic atrophy and mitochondrial network fragmentation. Elife. 2016; 5:e16078. doi: 10.7554/eLife.16078 27495975

65. Stiburek L, Cesnekova J, Kostkova O, Fornuskova D, Vinsova K, Wenchich L, et al. YME1L controls the accumulation of respiratory chain subunits and is required for apoptotic resistance, cristae morphogenesis, and cell proliferation. Mol Biol Cell. 2012; 23(6): 1010–23. doi: 10.1091/mbc.E11-08-0674 22262461

66. Vishnivetskaya GB, Skrinskaya JA, Seif I, Popova NK. Effect of MAO A deficiency on different kinds of aggression and social investigation in mice. Aggress Behav. 2007; 33(1): 1–6. doi: 10.1002/ab.20161 17441000

67. Brunner HG, Nelen M, Breakefield XO, Ropers HH, van Oost BA. Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A. Science. 1993; 262(5133): 578–80. doi: 10.1126/science.8211186 8211186

68. Gupta V, Khan AA, Sasi BK, Mahapatra NR. Molecular mechanism of monoamine oxidase A gene regulation under inflammation and ischemia-like conditions: key roles of the transcription factors GATA2, Sp1 and TBP. J Neurochem. 2015; 134(1): 21–38. doi: 10.1111/jnc.13099 25810277

69. Okada Y, Wu D, Trynka G, Raj T, Terao C, Ikan K, et al. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature. 2014; 506: 376–81. doi: 10.1038/nature12873 24390342

70. Shannon CP, Balshaw R, Chen V, Hollander Z, Toma M, McManus BM, et al. Enumerateblood–an R Package to Estimate the Cellular Composition of Whole Blood from Affymetrix Gene ST Gene Expression Profiles. BMC Genomics. 2017; 18: 43. doi: 10.1186/s12864-016-3460-1 28061752

71. Auman JT, Church R, Lee SY, Watson MA, Fleshman JW, Mcleod HL. Celecoxib Pre-Treatment in Human Colorectal Adenocarcinoma Patients Is Associated with Gene Expression Alterations Suggestive of Diminished Cellular Proliferation. Eur J Cancer. 2008; 44(12): 1754–60. doi: 10.1016/j.ejca.2008.05.010 18653328

72. Ducreux J, Durez P, Galant C, Nzeusseu Toukap A, Van den Eynde B, Houssiau FA, et al. Global Molecular Effects of Tocilizumab Therapy in Rheumatoid Arthritis Synovium. Arthritis Rheumatol. 2014; 66(1): 15–23. doi: 10.1002/art.38202 24449571

73. Barabási A-L, Gulbahce N, Loscalzo J. Network medicine: a network-based approach to human disease. Nat Rev Genet. 2011; 12: 56–58. doi: 10.1038/nrg2918 21164525

74. Qin S, Chock PB. Bruton’s tyrosine kinase is essential for hydrogen peroxide-induced calcium signaling. Biochemistry. 2001; 40(27): 8085–91. doi: 10.1021/bi0100788 11434777

75. Olofsson MH, Havelka AM, Brnjic S, Shoshan MC, Linder S. Charting calcium-regulated apoptosis pathways using chemical biology: role of calmodulin kinase II. BMC Chem Biol. 2008;8:2. doi: 10.1186/1472-6769-8-2 18673549

76. Jang D, Murrell GAC. Nitric oxide in arthritis. Free Radic Biol Med. 1998; 24(9): 1511–9. doi: 10.1016/s0891-5849(97)00459-0 9641270

77. van’t Hof RJ, Hocking L, Wright PK, Ralston SH. Nitric oxide is a mediator of apoptosis in the rheumatoid joint. Rheumatology. 2000; 39: 1004–8. doi: 10.1093/rheumatology/39.9.1004 10986306

78. Sakurai H, Kohsaka H, Liu MF, Higashiyama H, Hirata Y, Kanno K, et al. Nitric oxide production and inducible nitric oxide synthase expression in inflammatory arthritides. J Clin Invest. 1995; 96(5): 2357–63. doi: 10.1172/JCI118292 7593623

79. Dey P, Panga V, Raghunathan S. A cytokine signaling network for the regulation of inducible nitric oxide synthase expression in rheumatoid arthritis. Plos One. 2016; 11(9): e0161306. doi: 10.1371/journal.pone.0161306 27626941

80. Bauerová K, Bezek Š. Role of reactive oxygen and nitrogen species in etiopathogenesis of rheumatoid arthritis. Gen Physiol Biophys. 1999; 18: 15–20.

81. Phillips DC, Irundika Dias HK, Kitas GD, Griffiths HR. Aberrant reactive oxygen and nitrogen species generation in rheumatoid arthritis (RA): causes and consequences for immune function, cell survival, and therapeutic intervention. Antioxid Redox Signal. 2010; 12(6): 743–85. doi: 10.1089/ars.2009.2607 19686039

82. Nakahira K, Hisata S, Choi AMK. The roles of mitochondrial damage-associated molecular patterns in diseases. Antioxid Redox Signal. 2015; 23: 1329–50. doi: 10.1089/ars.2015.6407 26067258

83. Panga V, Raghunathan S. A cytokine protein-protein interaction network for identifying key molecules in rheumatoid arthritis. Plos One. 2018; 13(6): e0199530. doi: 10.1371/journal.pone.0199530 29928007

84. Zhu N, Hou J, Wu Y, Li G, Liu J, Ma G, et al. Identification of key genes in rheumatoid arthritis and osteoarthritis based on bioinformatics analysis. Medicine. 2018; 97(22): e10997. doi: 10.1097/MD.0000000000010997 29851858

85. Zhou WZ, Miao LG, Yuan H. Identification of significant ego networks and pathways in rheumatoid arthritis. J Can Res Ther. 2018; 14: 1024–8.

86. Sun Z, Wang W, Yu D, Mao Y. Differentially expressed genes between systemic sclerosis and rheumatoid arthritis. Hereditas. 2019; 156: 17. doi: 10.1186/s41065-019-0091-y 31178673

87. Zhang C, Guan D, Jiang M, Liang C, Li L, Zhao N, et al. Efficacy of leflunomide combined with ligustrazine in the treatment of rheumatoid arthritis: prediction with network pharmacology and validation in a clinical trial. Chin Med. 2019; 14: 26. doi: 10.1186/s13020-019-0247-8 31388350

88. Toro-Domínguez D, Carmona-Sáez P, Alarcón-Riquelme ME. Shared signatures between rheumatoid arthritis, systemic lupus erythematosus and Sjögren’s syndrome uncovered through gene expression meta-analysis. Arthritis Res Ther. 2014; 16: 489. doi: 10.1186/s13075-014-0489-x 25466291

89. Sawamukai N, Saito K, Yamaoka K, Nakayamada S, Ra C, Tanaka Y. Leflunomide inhibits PDK1/Akt pathway and induces apoptosis of human mast cells. J Immunol. 2007; 179(10): 6479–84. doi: 10.4049/jimmunol.179.10.6479 17982036

90. Sun C, Sun Y, Jiang D, Bao G, Zhu X, Xu D, et al. PDK1 promotes the inflammatory progress of fibroblast-like synoviocytes by phosphorylating RSK2. Cell Immunol. 2017; 315: 27–33. doi: 10.1016/j.cellimm.2016.10.007 28314444

91. Del Rey MJ, Izquierdo E, Usategui A, Gonzalo E, Blanco FJ, Acquadro F, et al. The transcriptional response of normal and rheumatoid arthritis synovial fibroblasts to hypoxia. Arthritis Rheum. 2010; 62(12): 3584–94. doi: 10.1002/art.27750 20848564

92. Tominaga M, Kurihara H, Honda S, Amakawa G, Sakai T, Tomooka Y. Molecular characterization of mitocalcin, a novel mitochondrial Ca2+-binding protein with EF-hand and coiled-coil domains. J Neurochem. 2006; 96(1): 292–304. doi: 10.1111/j.1471-4159.2005.03554.x 16336229

93. Wall VZ, Barnhart S, Kramer F, Kanter JE, Vivekanandan-Giri A, Pennathur S, et al. Inflammatory stimuli induce acyl-CoA thioesterase 7 and remodeling of phospholipids containing unsaturated long (≥C20)-acyl chains in macrophages. J Lipid Res. 2017; 58: 1174–85. doi: 10.1194/jlr.M076489 28416579

94. Tamiya G, Shinya M, Imanishi T, Ikuta T, Makino S, Okamoto K, et al. Whole genome association study of rheumatoid arthritis using 27039 microsatellites. Hum Mol Genet. 2005; 14(16): 2305–21. doi: 10.1093/hmg/ddi234 16000323

95. Fariss MW, Chan CB, Patel M, Van Houten B, Orrenius S. Role of mitochondria in toxic oxidative stress. Mol Interv. 2005; 5(2): 94–111. doi: 10.1124/mi.5.2.7 15821158

96. Schroecksnadel K, Kaser S, Ledochowski M, Neurauter G, Mur E, Herold M, et al. Increased degradation of tryptophan in blood of patients with rheumatoid arthritis. J Rheumatol. 2003; 30: 1935–9. 12966593

97. Kolodziej L. An exploratory study of the interplay between decreased concentration of tryptophan, accumulation of kynurenines, and inflammatory arthritis. IUBMB Life. 2012; 64(12): 983–87. doi: 10.1002/iub.1092 23124849

98. Taysi S, Polat F, Gul M, Sari RA, Bakan E. Lipid peroxidation, some extracellular antioxidants, and antioxidant enzymes in serum of patients with rheumatoid arthritis. Rheumatol Int. 2002; 21(5): 200–4. doi: 10.1007/s00296-001-0163-x 11958437

99. Marklund SL, Bjelle A, Elmqvist LG. Superoxide dismutase isoenzymes of the synovial fluid in rheumatoid arthritis and in reactive arthritides. Ann Rheum Dis. 1986; 45: 847–51. doi: 10.1136/ard.45.10.847 3789819

100. Ozturk HS, Cimen MY, Cimen OB, Kacmaz M, Durak I. Oxidant/antioxidant status of plasma samples from patients with rheumatoid arthritis. Rheumatol Int. 1999; 19: 35–37. doi: 10.1007/s002960050097 10651080

101. Vainio U. Leucineaminopeptidase in rheumatoid arthritis. Ann Rheum Dis. 1970; 29: 434.


Článek vyšel v časopise

PLOS One


2019 Číslo 11
Nejčtenější tento týden
Nejčtenější v tomto čísle
Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

KOST
Koncepce osteologické péče pro gynekology a praktické lékaře
nový kurz
Autoři: MUDr. František Šenk

Sekvenční léčba schizofrenie
Autoři: MUDr. Jana Hořínková

Hypertenze a hypercholesterolémie – synergický efekt léčby
Autoři: prof. MUDr. Hana Rosolová, DrSc.

Svět praktické medicíny 5/2023 (znalostní test z časopisu)

Imunopatologie? … a co my s tím???
Autoři: doc. MUDr. Helena Lahoda Brodská, Ph.D.

Všechny kurzy
Kurzy Podcasty Doporučená témata Časopisy
Přihlášení
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

#ADS_BOTTOM_SCRIPTS#