Molecular diagnostics of calcineurin-related pathologies

Clinical Chemistry

Volumn 58, Issue 3, 2012, Pages 511-522

  Musson, Ruben E A ^a   Cobbaert, Christa M ^a   Smit, Nico P M ^a  

^a LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

CALCINEURIN; CALCINEURIN INHIBITOR; CYCLOSPORIN A; IRON; TACROLIMUS; TRANSCRIPTION FACTOR NFAT; TRANSFORMING GROWTH FACTOR BETA; TRANSIENT RECEPTOR POTENTIAL CHANNEL; VOCLOSPORIN; ZINC;

ATOPIC DERMATITIS; CALCIUM BINDING; CELL MATURATION; DRUG MECHANISM; ENZYME KINETICS; EYE INFLAMMATION; HUMAN; IMMUNE RESPONSE; KIDNEY DISEASE; KIDNEY FIBROSIS; LUPUS ERYTHEMATOSUS; MOLECULAR DIAGNOSIS; NONHUMAN; OSTEOPOROSIS; PANCREAS ISLET BETA CELL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PSORIASIS; REVIEW; RHEUMATOID ARTHRITIS; SKIN CANCER; SKIN HYPERTROPHY;

CALCINEURIN; CYCLOSPORINE; ENZYME INHIBITORS; HUMANS; PATHOLOGY, MOLECULAR; SIGNAL TRANSDUCTION; TACROLIMUS;

EID: 84857840998     PISSN: 00099147     EISSN: 15308561     Source Type: Journal    
DOI: 10.1373/clinchem.2011.167296     Document Type: Review

References (140)

1. Musson RE, Smit NP. Regulatory mechanisms of calcineurin phosphatase activity. Curr Med Chem 2011;18:301-15.
2. Rusnak F, Mertz P. Calcineurin: form and function. Physiol Rev 2000;80:1483-521.
3. Perrino BA, Wilson AJ, Ellison P, Clapp LH. Substrate selectivity and sensitivity to inhibition by FK506 and cyclosporin A of calcineurin heterodimers composed of the α or β catalytic subunit. Eur J Biochem 2002;269:3540-8. (Pubitemid 34988998)
4. Gooch JL. An emerging role for calcineurin Aα in the development and function of the kidney. Am J Physiol Renal Physiol 2006;290:F769-76. (Pubitemid 43724933)
5. Bueno OF, Brandt EB, Rothenberg ME, Molkentin JD. Defective T cell development and function in calcineurin Aβ-deficient mice. Proc Natl Acad Sci U S A 2002;99:9398-403. (Pubitemid 34764625)
6. 2+/calcineurin-NFAT-mediated signaling. Mol Cells 2004;18:1-9.
7. Wu H, Peisley A, Graef IA, Crabtree GR. NFAT signaling and the invention of vertebrates. Trends Cell Biol 2007;17:251-60. (Pubitemid 46829850)
8. Rao A, Luo C, Hogan PG. Transcription factors of the NFAT family: regulation and function. Annu Rev Immunol 1997;15:707-47. (Pubitemid 27169297)
9. Tanabe K. Calcineurin inhibitors in renal transplantation: What is the best option? Drugs 2003;63:1535-48. (Pubitemid 36976137)
10. Reynolds NJ, Al-Daraji WI. Calcineurin inhibitors and sirolimus: mechanisms of action and applications in dermatology. Clin Exp Dermatol 2002; 27:555-61. (Pubitemid 35463871)
11. Luger T, Paul C. Potential new indications of topical calcineurin inhibitors. Dermatology 2007;215(Suppl 1):45-54. (Pubitemid 350308379)
12. Shaw KT, Ho AM, Raghavan A, Kim J, Jain J, Park J, et al. Immunosuppressive drugs prevent a rapid dephosphorylation of transcription factor NFAT1 in stimulated immune cells. Proc Natl Acad Sci U S A 1995;92:11205-9.
13. Chi P, Greengard P, Ryan TA. Synaptic vesicle mobilization is regulated by distinct synapsin I phosphorylation pathways at different frequencies. Neuron 2003;38:69-78. (Pubitemid 36423354)
14. Seki K, Chen HC, Huang KP. Dephosphorylation of protein kinase C substrates, neurogranin, neuromodulin, and MARCKS, by calcineurin and protein phosphatases 1 and 2A. Arch Biochem Biophys 1995;316:673-9.
15. Schwartz N, Schohl A, Ruthazer ES. Neural activity regulates synaptic properties and dendritic structure in vivo through calcineurin/NFAT signaling. Neuron 2009;62:655-69.
16. 2+ channel activity and nuclear signaling. Neuron 2007;55:261-75.
17. Kao SC, Wu H, Xie J, Chang CP, Ranish JA, Graef IA, Crabtree GR. Calcineurin/NFAT signaling is required for neuregulin-regulated Schwann cell differentiation. Science 2009;323:651-4.
18. Liu YL, Fann CS, Liu CM, Chang CC, Yang WC, Hung SI, et al. More evidence supports the association of PPP3CC with schizophrenia. Mol Psychiatry 2007;12:966-74. (Pubitemid 47482692)
19. Yamada K, Gerber DJ, Iwayama Y, Ohnishi T, Ohba H, Toyota T, et al. Genetic analysis of the calcineurin pathway identifies members of the EGR gene family, specifically EGR3, as potential susceptibility candidates in schizophrenia. Proc Natl Acad Sci U S A 2007;104:2815-20. (Pubitemid 46327962)
20. 2+ dysregulation with brain aging. J Neurosci 2001;21:4066-73.
21. Wu HY, Tomizawa K, Oda Y, Wei FY, Lu YF, Matsushita M, et al. Critical role of calpainmediated cleavage of calcineurin in excitotoxic neurodegeneration. J Biol Chem 2004;279: 4929-40. (Pubitemid 38199089)
22. Agbas A, Hui D, Wang X, Tek V, Zaidi A, Michaelis EK. Activation of brain calcineurin (Cn) by Cu-Zn superoxide dismutase (SOD1) depends on direct SOD1-Cn protein interactions occurring in vitro and in vivo. Biochem J 2007;405: 51-9. (Pubitemid 46999924)
23. Sklar EM. Post-transplant neurotoxicity: What role do calcineurin inhibitors actually play? AJNR Am J Neuroradiol 2006;27:1602-3. (Pubitemid 44413531)
24. Bahi A, Mineur YS, Picciotto MR. Blockade of protein phosphatase 2B activity in the amygdala increases anxiety-and depression-like behaviors in mice. Biol Psychiatry 2009;66:1139-46.
25. Kung L, Batiuk TD, Palomo-Pinon S, Noujaim J, Helms LM, Halloran PF. Tissue distribution of calcineurin and its sensitivity to inhibition by cyclosporine. Am J Transplant 2001;1:325-33. (Pubitemid 33681696)
26. Harris CD, Ermak G, Davies KJ. Multiple roles of the DSCR1 (Adapt78 or RCAN1) gene and its protein product calcipressin 1 (or RCAN1) in disease. Cell Mol Life Sci 2005;62:2477-86. (Pubitemid 41801100)
27. Park J, Oh Y, Chung KC. Two key genes closely implicated with the neuropathological characteristics in Down syndrome: DYRK1A and RCAN1. BMB Rep 2009;42:6-15.
28. Arron JR, Winslow MM, Polleri A, Chang CP, Wu H, Gao X, et al. NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21. Nature 2006;441:595-600. (Pubitemid 43927286)
29. Baek KH, Zaslavsky A, Lynch RC, Britt C, Okada Y, Siarey RJ, et al. Down's syndrome suppression of tumour growth and the role of the calcineurin inhibitor DSCR1. Nature 2009;459: 1126-30.
30. Luo J, Ma J, Yu DY, Bu F, Zhang W, Tu LH, Wei Q. Infusion of FK506, a specific inhibitor of calcineurin, induces potent tau hyperphosphorylation in mouse brain. Brain Res Bull 2008;76: 464-8.
31. Lian Q, Ladner CJ, Magnuson D, Lee JM. Selective changes of calcineurin (protein phosphatase 2B) activity in Alzheimer's disease cerebral cortex. Exp Neurol 2001;167:158-65. (Pubitemid 32066418)
32. Sun X, Wu Y, Chen B, Zhang Z, Zhou W, Tong Y, et al. Regulator of calcineurin 1 (RCAN1) facilitates neuronal apoptosis through caspase-3 activation. J Biol Chem 2011;286:9049-62.
33. Margallo-Lana M, Morris CM, Gibson AM, Tan AL, Kay DW, Tyrer SP, et al. Influence of the amyloid precursor protein locus on dementia in Down syndrome. Neurology 2004;62:1996-8. (Pubitemid 38738210)
34. Ermak G, Hench KJ, Chang KT, Sachdev S, Davies KJ. Regulator of calcineurin (RCAN1-1L) is deficient in Huntington disease and protective against mutant huntingtin toxicity in vitro. J Biol Chem 2009;284:11845-53.
35. Pineda JR, Pardo R, Zala D, Yu H, Humbert S, Saudou F. Genetic and pharmacological inhibition of calcineurin corrects the BDNF transport defect in Huntington's disease. Mol Brain 2009; 2:33.
36. Gerard M, Deleersnijder A, Daniëls V, Schreurs S, Munck S, Reumers V, et al. Inhibition of FK506 binding proteins reduces α-synuclein aggregation and Parkinson's disease-like pathology. J Neurosci 2010;30:2454-63.
37. Redmon JB, Olson LK, Armstrong MB, Greene MJ, Robertson RP. Effects of tacrolimus (FK506) on human insulin gene expression, insulin mRNA levels, and insulin secretion in HIT-T15 cells. J Clin Invest 1996;98:2786-93. (Pubitemid 26427406)
38. Heisel O, Heisel R, Balshaw R, Keown P. New onset diabetes mellitus in patients receiving calcineurin inhibitors: a systematic review and meta-analysis. Am J Transplant 2004;4:583-95. (Pubitemid 38523581)
39. 2+-responsive pathway involving calcineurin and nuclear factor of activated T cells. Mol Endocrinol 2001;15:1758-67.
40. Heit JJ, Apelqvist AA, Gu X, Winslow MM, Neilson JR, Crabtree GR, Kim SK. Calcineurin/NFAT signalling regulates pancreatic β-cell growth and function. Nature 2006;443:345-9. (Pubitemid 44435154)
41. Heit JJ. Calcineurin/NFAT signaling in the β-cell: from diabetes to new therapeutics. Bioessays 2007;29:1011-21. (Pubitemid 47522841)
42. Bernal-Mizrachi E, Cras-Méneur C, Ye BR, Johnson JD, Permutt MA. Transgenic overexpression of active calcineurin in β-cells results in decreased β-cell mass and hyperglycemia. PLoS One 2010;5:e11969.
43. Yang TT, Suk HY, Yang X, Olabisi O, Yu RY, Durand J, et al. Role of transcription factor NFAT in glucose and insulin homeostasis. Mol Cell Biol 2006;26:7372-87. (Pubitemid 44547690)
44. Yu AR, Xin HW, Wu XC, Fan X, Liu HM, Li G, Bai Y. Adiponectin gene polymorphisms are associated with posttransplantation diabetes mellitus in Chinese renal allograft recipients. Transplant Proc 2011;43:1607-11.
45. Sankaranarayanan TK, Sethi BK, Subramanyam C. Serum calcineurin activity in relation to oxidative stress and glycemic control in type II diabetes mellitus. Clin Biochem 2005;38:218-22. (Pubitemid 40222319)
46. Pernu HE, Pernu LM, Huttunen KR, Nieminen PA, Knuuttila ML. Gingival overgrowth among renal transplant recipients related to immunosuppressive medication and possible local background factors. J Periodontol 1992;63:548-53.
47. Fisher GJ, Duell EA, Nickoloff BJ, Annesley TM, Kowalke JK, Ellis CN, Voorhees JJ. Levels of cyclosporin in epidermis of treated psoriasis patients differentially inhibit growth of keratinocytes cultured in serum free versus serum containing media. J Invest Dermatol 1988;91: 142-6.
48. Buell JF, Gross TG, Woodle ES. Malignancy after transplantation. Transplantation 2005;80: S254-64. (Pubitemid 41552912)
49. Akool el-S, Doller A, Babelova A, Tsalastra W, Moreth K, Schaefer L, et al. Molecular mechanisms of TGF β receptor-triggered signaling cascades rapidly induced by the calcineurin inhibitors cyclosporin A and FK506. J Immunol 2008; 181:2831-45.
50. Al-Daraji WI, Grant KR, Ryan K, Saxton A, Reynolds NJ. Localization of calcineurin/NFAT in human skin and psoriasis and inhibition of calcineurin/NFAT activation in human keratinocytes by cyclosporin A. J Invest Dermatol 2002;118:779-88. (Pubitemid 34526539)
51. Al-Daraji WI, Malak TT, Prescott RJ, Abdellaoui A, Ali MM, Dabash T, et al. Expression, localisation and functional activation of NFAT-2 in normal human skin, psoriasis, and cultured keratocytes. Int J Clin Exp Med 2009;2:176-92.
52. Smit NP, Van Rossum HH, Romijn FP, Sellar KJ, Breetveld M, Gibbs S, Van Pelt J. Calcineurin activity and inhibition in skin and (epi)dermal cell cultures. J Invest Dermatol 2008;128:1686-90. (Pubitemid 351847373)
53. Musson RE, Hensbergen PJ, Westphal AH, Temmink WP, Deelder AM, van Pelt J, et al. UVA1 radiation inhibits calcineurin through oxidative damage mediated by photosensitization. Free Radic Biol Med 2011;50:1392-9.
54. Santini MP, Talora C, Seki T, Bolgan L, Dotto GP. Cross talk among calcineurin, Sp1/Sp3, and NFAT in control of p21(WAF1/CIP1) expression in keratinocyte differentiation. Proc Natl Acad Sci U S A 2001;98:9575-80. (Pubitemid 32769345)
55. Mammucari C, Tommasi di Vignano A, Sharov AA, Neilson J, Havrda MC, Roop DR, et al. Integration of Notch 1 and calcineurin/NFAT signaling pathways in keratinocyte growth and differentiation control. Dev Cell 2005;8:665-76. (Pubitemid 40585290)
56. Thoms KM, Kuschal C, Oetjen E, Mori T, Kobayashi N, Laspe P, et al. Cyclosporin A, but not everolimus, inhibits DNA repair mediated by calcineurin: implications for tumorigenesis under immunosuppression. Exp Dermatol 2011;20: 232-6.
57. 2+-induced apoptosis through calcineurin dephosphorylation of BAD. Science 1999;284:339-43.
58. Shibasaki F, Kondo E, Akagi T, McKeon F. Suppression of signalling through transcription factor NF-AT by interactions between calcineurin and Bcl-2. Nature 1997;386:728-31. (Pubitemid 27193495)
59. Wu X, Nguyen BC, Dziunycz P, Chang S, Brooks Y, Lefort K, et al. Opposing roles for calcineurin and ATF3 in squamous skin cancer. Nature 2010;465:368-72.
60. Schulz RA, Yutzey KE. Calcineurin signaling and NFAT activation in cardiovascular and skeletal muscle development. Dev Biol 2004;266:1-16.
61. de la Pompa JL, Timmerman LA, Takimoto H, Yoshida H, Elia AJ, Samper E, et al. Role of the NF-ATc transcription factor in morphogenesis of cardiac valves and septum. Nature 1998;392: 182-6.
62. Maillet M, Davis J, Auger-Messier M, York A, Osinska H, Piquereau J, et al. Heart-specific deletion of CnB1 reveals multiple mechanisms whereby calcineurin regulates cardiac growth and function. J Biol Chem 2010;285:6716-24.
63. Schaeffer PJ, Desantiago J, Yang J, Flagg TP, Kovacs A, Weinheimer CJ, et al. Impaired contractile function and calcium handling in hearts of cardiac-specific calcineurin b1-deficient mice. Am J Physiol Heart Circ Physiol 2009;297: H1263-73.
64. Molkentin JD, Lu JR, Antos CL, Markham B, Richardson J, Robbins J, et al. A calcineurin-dependent transcriptional pathway for cardiac hypertrophy. Cell 1998;93:215-28. (Pubitemid 28180855)
65. Bueno OF, Lips DJ, Kaiser RA, Wilkins BJ, Dai YS, Glascock BJ, et al. Calcineurin Aβ gene targeting predisposes the myocardium to acute ischemia-induced apoptosis and dysfunction. Circ Res 2004;94:91-9. (Pubitemid 38064103)
66. Wilkins BJ, Dai YS, Bueno OF, Parsons SA, Xu J, Plank DM, et al. Calcineurin/NFAT coupling participates in pathological, but not physiological, cardiac hypertrophy. Circ Res 2004;94:110-8. (Pubitemid 38064105)
67. Bourajjaj M, Armand AS, da Costa Martins PA, Weijts B, van der Nagel R, Heeneman S, et al. NFATc2 is a necessary mediator of calcineurin-dependent cardiac hypertrophy and heart failure. J Biol Chem 2008;283:22295-303.
68. Yang J, Rothermel B, Vega RB, Frey N, McKinsey TA, Olson EN, et al. Independent signals control expression of the calcineurin inhibitory proteins MCIP1 and MCIP2 in striated muscles. Circ Res 2000;87:E61-8.
69. Vega RB, Rothermel BA, Weinheimer CJ, Kovacs A, Naseem RH, Bassel-Duby R, et al. Dual roles of modulatory calcineurin-interacting protein 1 in cardiac hypertrophy. Proc Natl Acad Sci U S A 2003;100:669-74. (Pubitemid 36126110)
70. Eder P, Molkentin JD. TRPC channels as effectors of cardiac hypertrophy. Circ Res 2011;108: 265-72.
71. Ritter O, Hack S, Schuh K, Röthlein N, Perrot A, Osterziel KJ, et al. Calcineurin in human heart hypertrophy. Circulation 2002;105:2265-9. (Pubitemid 34535336)
72. Burkard N, Becher J, Heindl C, Neyses L, Schuh K, Ritter O. Targeted proteolysis sustains calcineurin activation. Circulation 2005;111:1045-53. (Pubitemid 40354524)
73. Myers BD, Ross J, Newton L, Luetscher J, Perlroth M. Cyclosporine- associated chronic nephropathy. N Engl J Med 1984;311:699-705. (Pubitemid 14074555)
74. Naesens M, Kuypers DR, Sarwal M. Calcineurin inhibitor nephrotoxicity. Clin J Am Soc Nephrol 2009;4:481-508.
75. Bobadilla NA, Gamba G. New insights into the pathophysiology of cyclosporine nephrotoxicity: a role of aldosterone. Am J Physiol Renal Physiol 2007;293:F2-9. (Pubitemid 47345003)
76. English J, Evan A, Houghton DC, Bennett WM. Cyclosporine-induced acute renal dysfunction in the rat. Evidence of arteriolar vasoconstriction with preservation of tubular function. Transplantation 1987;44:135-41.
77. Shihab FS, Bennett WM, Tanner AM, Andoh TF. Angiotensin II blockade decreases TGF-β1 and matrix proteins in cyclosporine nephropathy. Kidney Int 1997;52:660-73. (Pubitemid 27402364)
78. Han JS, Choi BS, Yang CW, Kim YS. Aldosterone-induced TGF-β1 expression is regulated by mitogen-activated protein kinases and activator protein-1 in mesangial cells. J Korean Med Sci 2009;24(Suppl):S195-203.
79. Chapman JR. Chronic calcineurin inhibitor nephrotoxicity-lest we forget. Am J Transplant 2011;11:693-7.
80. Burn SF, Webb A, Berry RL, Davies JA, Ferrer-Vaquer A, Hadjantonakis AK, et al. Calcium/NFAT signalling promotes early nephrogenesis. Dev Biol 2011;352:288-98.
81. Tendron A, Decramer S, Justrabo E, Gouyon JB, Semama DS, Gilbert T. Cyclosporin A administration during pregnancy induces a permanent nephron deficit in young rabbits. J Am Soc Nephrol 2003;14:3188-96. (Pubitemid 37509294)
82. Liu H, Ye W, Guan G, Dong Z, Jia Z, Yang T. Developmental regulation of calcineurin isoforms in the rodent kidney: association with COX-2. Am J Physiol Renal Physiol 2007;293: F1898-904. (Pubitemid 350179614)
83. Puri S, Magenheimer BS, Maser RL, Ryan EM, Zien CA, Walker DD, et al. Polycystin-1 activates the calcineurin/NFAT (nuclear factor of activated T-cells) signaling pathway. J Biol Chem 2004; 279:55455-64. (Pubitemid 40066546)
84. López-Rodríguez C, Antos CL, Shelton JM, Richardson JA, Lin F, Novobrantseva TI, et al. Loss of NFAT5 results in renal atrophy and lack of tonicity-responsive gene expression. Proc Natl Acad Sci U S A 2004;101:2392-7. (Pubitemid 38269322)
85. Li SZ, McDill BW, Kovach PA, Ding L, Go WY, Ho SN, Chen F. Calcineurin-NFATc signaling pathway regulates AQP2 expression in response to calcium signals and osmotic stress. Am J Physiol Cell Physiol 2007;292:C1606-16. (Pubitemid 47080556)
86. Damiano S, Scanni R, Ciarcia R, Florio S, Capasso G. Regulation of sodium transporters in the kidney during cyclosporine treatment. J Nephrol 2010;23(Suppl 16):S191-8.
87. Hasler U. Interplay between TonEBP and calcineurin-NFATc signaling pathways: a means of optimizing water reabsorption? Focus on "Calcineurin-NFATc signaling pathway regulates AQP2 expression in response to calcium signals and osmotic stress." Am J Physiol Cell Physiol 2007;292:C1581-2. (Pubitemid 47080539)
88. Grossmann C, Wuttke M, Ruhs S, Seiferth A, Mildenberger S, Rabe S, et al. Mineralocorticoid receptor inhibits CREB signaling by calcineurin activation. FASEB J 2010;24:2010-9.
89. Gooch JL, Toro JJ, Guler RL, Barnes JL. Calcineurin A-α but not A-β is required for normal kidney development and function. Am J Pathol 2004;165:1755-65. (Pubitemid 39435172)
90. Gooch JL, Roberts BR, Cobbs SL, Tumlin JA. Loss of the α-isoform of calcineurin is sufficient to induce nephrotoxicity and altered expression of transforming growth factor-β. Transplantation 2007;83:439-47. (Pubitemid 46667848)
91. Uchino H, Elmé r E, Uchino K, Li PA, He QP, Smith ML, Siesjö BK. Amelioration by cyclosporin A of brain damage in transient forebrain ischemia in the rat. Brain Res 1998;812:216-26. (Pubitemid 29005351)
92. Chen S, Hong SW, Iglesias-de la Cruz MC, Isono M, Casaretto A, Ziyadeh FN. The key role of the transforming growth factor-β system in the pathogenesis of diabetic nephropathy. Ren Fail 2001;23:471-81. (Pubitemid 32692282)
93. Li J, Liu B, Yan LN, Wang LL, Lau WY, Li B, et al. Microproteinuria for detecting calcineurin inhibitor-related nephrotoxicity after liver transplantation. World J Gastroenterol 2009;15: 2913-7.
94. Dieterle F, Perentes E, Cordier A, Roth DR, Verdes P, Grenet O, et al. Urinary clusterin, cystatin C, β2-microglobulin and total protein as markers to detect drug-induced kidney injury. Nat Biotechnol 2010;28:463-9.
95. Wasilewska A, Zoch-Zwierz W, Taranta-Janusz K, Michaluk-Skutnik J. Neutrophil gelatinase-associated lipocalin (NGAL): a new marker of cyclosporine nephrotoxicity? Pediatr Nephrol 2010;25:889-97.
96. Koyner JL, Vaidya VS, Bennett MR, Ma Q, Worcester E, Akhter SA, et al. Urinary biomarkers in the clinical prognosis and early detection of acute kidney injury. Clin J Am Soc Nephrol 2010;5:2154-65.
97. O'Connell S, Slattery C, Ryan MP, McMorrow T. Identification of novel indicators of cyclosporine A nephrotoxicity in a CD-1 mouse model. Toxicol Appl Pharmacol 2011;252:201-10.
98. Pallet N, Djamali A, Legendre C. Challenges in diagnosing acute calcineurin-inhibitor induced nephrotoxicity: from toxicogenomics to emerging biomarkers. Pharmacol Res 2011;64:25-30.
99. Kitahara K, Kawai S. Cyclosporine and tacrolimus for the treatment of rheumatoid arthritis. Curr Opin Rheumatol 2007;19:238-45. (Pubitemid 46597460)
100. Rodino MA, Shane E. Osteoporosis after organ transplantation. Am J Med 1998;104:459-69. (Pubitemid 28274851)
101. Sitara D, Aliprantis AO. Transcriptional regulation of bone and joint remodeling by NFAT. Immunol Rev 2010;233:286-300.
102. Stern PH. The calcineurin-NFAT pathway and bone: intriguing new findings. Mol Interv 2006; 6:193-6. (Pubitemid 44455200)
103. Auw-Hädrich C, Reinhard T. [Treatment of chronic blepharokeratoconjunctivitis with local calcineurin inhibitors]. Ophthalmologe 2009; 106:635-8 [German].
104. Cunningham MA, Austin BA, Li Z, Liu B, Yeh S, Chan CC, et al. LX211 (voclosporin) suppresses experimental uveitis and inhibits human T cells. Invest Ophthalmol Vis Sci 2009;50:249-55.
105. Kurji K, Sharma RK. Potential role of calcineurin in pathogenic conditions. Mol Cell Biochem 2010;338:133-41.
106. Huang W, Fileta JB, Dobberfuhl A, Filippopolous T, Guo Y, Kwon G, Grosskreutz CL. Calcineurin cleavage is triggered by elevated intraocular pressure, and calcineurin inhibition blocks retinal ganglion cell death in experimental glaucoma. Proc Natl Acad Sci U S A 2005;102: 12242-7. (Pubitemid 41291159)
107. Sanquer S, Schwarzinger M, Maury S, Yakouben K, Rafi H, Pautas C, et al. Calcineurin activity as a functional index of immunosuppression after allogeneic stem-cell transplantation. Transplantation 2004;77:854-8. (Pubitemid 38436823)
108. Fukudo M, Yano I, Masuda S, Fukatsu S, Katsura T, Ogura Y, et al. Pharmacodynamic analysis of tacrolimus and cyclosporine in living-donor liver transplant patients. Clin Pharmacol Ther 2005; 78:168-81. (Pubitemid 41112285)
109. Van Rossum HH. Pharmacodynamic monitoring of calcineurin inhibition therapy [PhD thesis]. Leiden, the Netherlands: Leiden University, 2010.
110. Pallen CJ, Wang JH. Calmodulin-stimulated dephosphorylation of p-nitrophenyl phosphate and free phosphotyrosine by calcineurin. J Biol Chem 1983;258:8550-3. (Pubitemid 13026698)
111. Yin M, Ochs RS. Mechanism for the paradoxical inhibition and stimulation of calcineurin by the immunosuppressive drug tacrolimus (FK506). Arch Biochem Biophys 2003;419:207-13. (Pubitemid 37329987)
112. Fruman DA, Pai SY, Klee CB, Burakoff SJ, Bierer BE. Measurement of calcineurin phosphatase activity in cell extracts. Methods 1996;9:146-54. (Pubitemid 26179415)
113. Koefoed-Nielsen PB, Karamperis N, Jørgensen KA. Validation of the calcineurin phosphatase assay. Clin Chem 2004;50:2331-7. (Pubitemid 39552169)
114. Sellar KJ, van Rossum HH, Romijn FP, Smit NP, de Fijter JW, van Pelt J. Spectrophotometric assay for calcineurin activity in leukocytes isolated from human blood. Anal Biochem 2006; 358:104-10. (Pubitemid 44511905)
115. Smit N, Musson R, Romijn F, van Rossum H, van Pelt J. Effects of ultraviolet A-1 radiation on calcineurin activity and cytokine production in (skin) cell cultures. Photochem Photobiol 2010; 86:360-6.
116. Blanchet B, Hulin A, Duvoux C, Astier A. Determination of serine/threonine protein phosphatase type 2B PP2B in lymphocytes by HPLC. Anal Biochem 2003;312:1-6. (Pubitemid 36015960)
117. Newman RH, Zhang J. Visualization of phosphatase activity in living cells with a FRET-based calcineurin activity sensor. Mol Biosyst 2008;4: 496-501. (Pubitemid 351706288)
118. 2+ oscillation. EMBO J 2003;22:3825-32.
119. Crabtree GR, Olson EN. NFAT signaling: choreographing the social lives of cells. Cell 2002; 109(Suppl):S67-79. (Pubitemid 34457853)
120. Hernández GL, Volpert OV, Iñiguez MA, Lorenzo E, Martínez-Martínez S, Grau R, et al. Selective inhibition of vascular endothelial growth factormediated angiogenesis by cyclosporin A: roles of the nuclear factor of activated T cells and cyclooxygenase 2. J Exp Med 2001;193:607-20. (Pubitemid 32539557)
121. Welge V, Fiege O, Lewczuk P, Mollenhauer B, Esselmann H, Klafki HW, et al. Combined CSF tau, p-tau181 and amyloid-β 38/40/42 for diagnosing Alzheimer's disease. J Neural Transm 2009;116:203-12.
122. Cruchaga C, Kauwe JS, Mayo K, Spiegel N, Bertelsen S, Nowotny P, et al. SNPs associated with cerebrospinal fluid phospho-tau levels influence rate of decline in Alzheimer's disease. PLoS Genet 2010;6:e1001101.
123. Biswas G, Anandatheerthavarada HK, Zaidi M, Avadhani NG. Mitochondria to nucleus stress signaling: a distinctive mechanism of NFκB/Rel activation through calcineurin-mediated inactivation of IκBβ. J Cell Biol 2003;161:507-19. (Pubitemid 36578576)
124. Stein CM, Murray JJ, Wood AJ. Inhibition of stimulated interleukin-2 production in whole blood: a practical measure of cyclosporine effect. Clin Chem 1999;45:1477-84. (Pubitemid 29419000)
125. Stalder M, Bîrsan T, Holm B, Haririfar M, Scandling J, Morris RE. Quantification of immunosuppression by flow cytometry in stable renal transplant recipients. Ther Drug Monit 2003;25: 22-7. (Pubitemid 36139821)
126. Hodge G, Hodge S, Reynolds P, Holmes M. Intracellular cytokines in blood T cells in lung transplant patients-a more relevant indicator of immunosuppression than drug levels. Clin Exp Immunol 2005;139:159-64. (Pubitemid 40066142)
127. Diehn M, Alizadeh AA, Rando OJ, Liu CL, Stankunas K, Botstein D, et al. Genomic expression programs and the integration of the CD28 costimulatory signal in T cell activation. Proc Natl Acad Sci U S A 2002;99:11796-801. (Pubitemid 34994478)
128. Press RR. Individualized dosing of calcineurin inhibitors in renal transplantation [PhD thesis]. Leiden, the Netherlands: Leiden University, 2011:142pp.
129. Giese T, Sommerer C, Zeier M, Meuer S. Approaches towards individualized immune intervention. Dig Dis 2010;28:45-50.
130. Dumont RJ, Ensom MH. Methods for clinical monitoring of cyclosporin in transplant patients. Clin Pharmacokinet 2000;38:427-47. (Pubitemid 30265262)
131. Press RR, Ploeger BA, den Hartigh J, van der Straaten T, van Pelt J, Danhof M, et al. Explaining variability in tacrolimus pharmacokinetics to optimize early exposure in adult kidney transplant recipients. Ther Drug Monit 2009;31:187-97.
132. von Ahsen N, Helmhold M, Schütz E, Eisenhauer T, Armstrong VW, Oellerich M. Cyclosporin A trough levels correlate with serum lipoproteins and apolipoproteins: implications for therapeutic drug monitoring of cyclosporin A. Ther Drug Monit 1997;19:140-5.
133. Yano I. Pharmacodynamic monitoring of calcineurin phosphatase activity in transplant patients treated with calcineurin inhibitors. Drug Metab Pharmacokinet 2008;23:150-7.
134. van Rossum HH, de Fijter JW, van Pelt J. Pharmacodynamic monitoring of calcineurin inhibition therapy: principles, performance, and perspectives. Ther Drug Monit 2010;32:3-10.
135. Giese T, Zeier M, Meuer S. Analysis of NFAT-regulated gene expression in vivo: a novel perspective for optimal individualized doses of calcineurin inhibitors. Nephrol Dial Transplant 2004;19(Suppl 4):iv55-60. (Pubitemid 39136707)
136. Sommerer C, Konstandin M, Dengler T, Schmidt J, Meuer S, Zeier M, Giese T. Pharmacodynamic monitoring of cyclosporine A in renal allograft recipients shows a quantitative relationship between immunosuppression and the occurrence of recurrent infections and malignancies. Transplantation 2006;82:1280-5. (Pubitemid 44832909)
137. Sommerer C, Giese T, Schmidt J, Meuer S, Zeier M. Ciclosporin A tapering monitored by NFAT-regulated gene expression: a new concept of individual immunosuppression. Transplantation 2008;85:15-21.
138. Sommerer C, Hartschuh W, Enk A, Meuer S, Zeier M, Giese T. Pharmacodynamic immune monitoring of NFAT-regulated genes predicts skin cancer in elderly long-term renal transplant recipients. Clin Transplant 2008;22:549-54.
139. Giese T, Sommerer C, Zeier M, Meuer S. Monitoring immunosuppression with measures of NFAT decreases cancer incidence. Clin Immunol 2009;132:305-11.
140. Marquet P. Counterpoint: Is pharmacokinetic or pharmacodynamic monitoring of calcineurin inhibition therapy necessary? Clin Chem 2010;56: 736-9.