Prenatal cadmium exposure dysregulates sonic hedgehog and Wnt/β-catenin signaling in the thymus resulting in altered thymocyte development

Toxicology and Applied Pharmacology

Volumn 242, Issue 2, 2010, Pages 136-145

  Hanson, Miranda L ^a   Brundage, Kathleen M ^a   Schafer, Rosana ^a   Tou, Janet C ^b   Barnett, John B ^a  

^a WEST VIRGINIA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b Forestry and Consumer Sciences   (United States)

Author keywords

Cadmium; Prenatal; Sonic hedgehog; Thymocyte development; Wnt

Indexed keywords

BETA CATENIN; CADMIUM; MYC PROTEIN; PROTEIN C FOS; PROTEIN PATCHED 1; SONIC HEDGEHOG PROTEIN; TRANSCRIPTION FACTOR GLI1; WNT PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; C57BL 6 MOUSE; CD4+ T LYMPHOCYTE; CELL MATURATION; CONCENTRATION RESPONSE; CONTROLLED STUDY; FEMALE; FLOW CYTOMETRY; GENE TARGETING; GENETIC TRANSCRIPTION; LYMPHOCYTE SUBPOPULATION; MOUSE; NEWBORN; NONHUMAN; PHENOTYPE; PRENATAL EXPOSURE; PROTEIN EXPRESSION; REAL TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; RNA TRANSLATION; SIGNAL TRANSDUCTION; THYMOCYTE; THYMUS FUNCTION; TISSUE LEVEL; WESTERN BLOTTING;

ANIMALS; BASE SEQUENCE; BETA CATENIN; BLOTTING, WESTERN; CADMIUM; DNA PRIMERS; FEMALE; FLOW CYTOMETRY; HEDGEHOG PROTEINS; MATERNAL EXPOSURE; MICE; MICE, INBRED C57BL; PREGNANCY; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; THYMUS GLAND; WNT PROTEINS;

ERINACEIDAE; MUS;

EID: 71049160384     PISSN: 0041008X     EISSN: 10960333     Source Type: Journal    
DOI: 10.1016/j.taap.2009.09.023     Document Type: Article

References (66)

1. Achanzar W.E., Achanzar K.B., Lewis J.G., Webber M.M., and Waalkes M.P. Cadmium induces c-myc, p53, and c-jun expression in normal human prostate epithelial cells as a prelude to apoptosis. Toxicol. Appl. Pharmacol. 164 (2000) 291-300
2. Agency for toxic substances and disease registry (ATSDR), 2007
3. Amit S., Hatzubai A., Birman Y., Andersen J.S., Ben-Shushan E., Mann M., Ben-Neriah Y., and Alkalay I. Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway. Genes Dev. 16 (2002) 1066-1076
4. Austin T.W., Solar G.P., Ziegler F.C., Liem L., and Matthews W. A role for the Wnt gene family in hematopoiesis: expansion of multilineage progenitor cells. Blood 89 (1997) 3624-3635
5. Behrens J., von Kries J.P., Kuhl M., Bruhn L., Wedlich D., Grosschedl R., and Birchmeier W. Functional interaction of beta-catenin with the transcription factor LEF-1. Nature 382 (1996) 638-642
6. Bhanot P., Brink M., Samos C.H., Hsieh J.C., Wang Y., Macke J.P., Andrew D., Nathans J., and Nusse R. A new member of the frizzled family from Drosophila functions as a Wingless receptor. Nature 382 (1996) 225-230
7. Borgman R.F., Au B., and Chandra R.K. Immunopathology of chronic cadmium administration in mice. Int. J. Immunopharmacol. 8 (1986) 813-817
8. Burke R., Nellen D., Bellotto M., Hafen E., Senti K.A., Dickson B.J., and Basler K. Dispatched, a novel sterol-sensing domain protein dedicated to the release of cholesterol-modified hedgehog from signaling cells. Cell 99 (1999) 803-815
9. Chen Y., and Struhl G. Dual roles for patched in sequestering and transducing Hedgehog. Cell 87 (1996) 553-563
10. Chen Y., and Struhl G. In vivo evidence that Patched and Smoothened constitute distinct binding and transducing components of a Hedgehog receptor complex. Development 125 (1998) 4943-4948
11. Ching W., and Nusse R. A dedicated Wnt secretion factor. Cell 125 (2006) 432-433
12. Cook M.E. Anthropogenic sources of cadmium in Canada. National Workshop on Cadmium Transport Into Plants (1995), Canadian Network of Toxicology Centres, Ottawa, Ontario, Canada
13. Dong S., Shen H.M., and Ong C.N. Cadmium-induced apoptosis and phenotypic changes in mouse thymocytes. Mol. Cell Biochem. 222 (2001) 11-20
14. Gao Z.H., Seeling J.M., Hill V., Yochum A., and Virshup D.M. Casein kinase I phosphorylates and destabilizes the beta-catenin degradation complex. Proc. Natl. Acad. Sci. U. S. A. 99 (2002) 1182-1187
15. Hattori N., Kawamoto H., Fujimoto S., Kuno K., and Katsura Y. Involvement of transcription factors TCF-1 and GATA-3 in the initiation of the earliest step of T cell development in the thymus. J. Exp. Med. 184 (1996) 1137-1147
16. Hovland Jr. D.N., Machado A.F., Scott Jr. W.J., and Collins M.D. Differential sensitivity of the SWV and C57BL/6 mouse strains to the teratogenic action of single administrations of cadmium given throughout the period of anterior neuropore closure. Teratology 60 (1999) 13-21
17. Ikeda S., Kishida S., Yamamoto H., Murai H., Koyama S., and Kikuchi A. Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin. EMBO J. 17 (1998) 1371-1384
18. Ingham P.W., and McMahon A.P. Hedgehog signaling in animal development: paradigms and principles. Genes Dev. 15 (2001) 3059-3087
19. Ioannidis V., Beermann F., Clevers H., and Held W. The beta-catenin-TCF-1 pathway ensures CD4(+)CD8(+) thymocyte survival. Nat. Immunol. 2 (2001) 691-697
20. Jacquillet G., Barbier O., Rubera I., Tauc M., Borderie A., Namorado M.C., Martin D., Sierra G., Reyes J.L., Poujeol P., and Cougnon M. Cadmium causes delayed effects on renal function in the offspring of cadmium-contaminated pregnant female rats. Am. J. Physiol. Renal. Physiol. 293 (2007) F1450-F1460
21. Jin P., and Ringertz N.R. Cadmium induces transcription of proto-oncogenes c-jun and c-myc in rat L6 myoblasts. J. Biol. Chem. 265 (1990) 14061-14064
22. Jin T., Lu J., and Nordberg M. Toxicokinetics and biochemistry of cadmium with special emphasis on the role of metallothionein. Neurotoxicology 19 (1998) 529-535
23. Joseph P., Muchnok T.K., Klishis M.L., Roberts J.R., Antonini J.M., Whong W.Z., and Ong T. Cadmium-induced cell transformation and tumorigenesis are associated with transcriptional activation of c-fos, c-jun, and c-myc proto-oncogenes: role of cellular calcium and reactive oxygen species. Toxicol. Sci. 61 (2001) 295-303
24. Lafuente A., Gonzalez-Carracedo A., Romero A., and Esquifino A.I. Effect of cadmium on lymphocyte subsets distribution in thymus and spleen. J. Physiol. Biochem. 59 (2003) 43-48
25. Lauwerys R., Buchet J.P., Roels H., Bernard A., and Gennart J.P. [Biological aspects of occupational exposure to cadmium and several other metals]. Rev. Epidemiol. Sante Publique 34 (1986) 280-285
26. Liu J., Liu Y., Habeebu S.S., and Klaassen C.D. Metallothionein-null mice are highly susceptible to the hematotoxic and immunotoxic effects of chronic CdCl2 exposure. Toxicol. Appl. Pharmacol. 159 (1999) 98-108
27. Livak K.J., and Schmittgen T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25 (2001) 402-408
28. Mackova N.O., Lenikova S., Fedorocko P., Brezani P., and Fedorockova A. Effects of cadmium on haemopoiesis in irradiated and non-irradiated mice: 2. Relationship to the number of circulating blood cells and haemopoiesis. Physiol. Res. 45 (1996) 101-106
29. Marigo V., Davey R.A., Zuo Y., Cunningham J.M., and Tabin C.J. Biochemical evidence that patched is the Hedgehog receptor. Nature 384 (1996) 176-179
30. Matsuoka M., and Call K.M. Cadmium-induced expression of immediate early genes in LLC-PK1 cells. Kidney Int. 48 (1995) 383-389
31. Minetti A., and Reale C.A. Sensorimotor developmental delays and lower anxiety in rats prenatally exposed to cadmium. J. Appl. Toxicol. 26 (2006) 35-41
32. Morselt A.F., Leene W., De Groot C., Kipp J.B., Evers M., Roelofsen A.M., and Bosch K.S. Differences in immunological susceptibility to cadmium toxicity between two rat strains as demonstrated with cell biological methods. Effect of cadmium on DNA synthesis of thymus lymphocytes. Toxicology 48 (1988) 127-139
33. Mulroy T., Xu Y., and Sen J.M. beta-Catenin expression enhances generation of mature thymocytes. Int. Immunol. 15 (2003) 1485-1494
34. Nordberg G.F. Lung cancer and exposure to environmental cadmium. Lancet Oncol. 7 (2006) 99-101
35. Novak A., and Dedhar S. Signaling through beta-catenin and Lef/Tcf. Cell Mol. Life Sci. 56 (1999) 523-537
36. Okamura R.M., Sigvardsson M., Galceran J., Verbeek S., Clevers H., and Grosschedl R. Redundant regulation of T cell differentiation and TCRalpha gene expression by the transcription factors LEF-1 and TCF-1. Immunity 8 (1998) 11-20
37. Oosterwegel M., van de Wetering M., Dooijes D., Klomp L., Winoto A., Georgopoulos K., Meijlink F., and Clevers H. Cloning of murine TCF-1, a T cell-specific transcription factor interacting with functional motifs in the CD3-epsilon and T cell receptor alpha enhancers. J. Exp. Med. 173 (1991) 1133-1142
38. Outram S.V., Varas A., Pepicelli C.V., and Crompton T. Hedgehog signaling regulates differentiation from double-negative to double-positive thymocyte. Immunity 13 (2000) 187-197
39. Pathak N., and Khandelwal S. Impact of cadmium in T lymphocyte subsets and cytokine expression: differential regulation by oxidative stress and apoptosis. Biometals 21 (2008) 179-187
40. Pepinsky R.B., Zeng C., Wen D., Rayhorn P., Baker D.P., Williams K.P., Bixler S.A., Ambrose C.M., Garber E.A., Miatkowski K., Taylor F.R., Wang E.A., and Galdes A. Identification of a palmitic acid-modified form of human sonic hedgehog. J. Biol. Chem. 273 (1998) 14037-14045
41. Pongracz J., Hare K., Harman B., Anderson G., and Jenkinson E.J. Thymic epithelial cells provide WNT signals to developing thymocytes. Eur. J. Immunol. 33 (2003) 1949-1956
42. Porter J.A., von Kessler D.P., Ekker S.C., Young K.E., Lee J.J., Moses K., and Beachy P.A. The product of hedgehog autoproteolytic cleavage active in local and long-range signalling. Nature 374 (1995) 363-366
43. Prozialeck W.C., Lamar P.C., and Lynch S.M. Cadmium alters the localization of N-cadherin, E-cadherin, and beta-catenin in the proximal tubule epithelium. Toxicol. Appl. Pharmacol. 189 (2003) 180-195
44. Schilham M.W., Wilson A., Moerer P., Benaissa-Trouw B.J., Cumano A., and Clevers H.C. Critical involvement of Tcf-1 in expansion of thymocytes. J. Immunol. 161 (1998) 3984-3991
45. Scott Jr. W.J., Schreiner C.M., Goetz J.A., Robbins D., and Bell S.M. Cadmium-induced postaxial forelimb ectrodactyly: association with altered sonic hedgehog signaling. Reprod. Toxicol. 19 (2005) 479-485
46. Shah D.K., Hager-Theodorides A.L., Outram S.V., Ross S.E., Varas A., and Crompton T. Reduced thymocyte development in sonic hedgehog knockout embryos. J. Immunol. 172 (2004) 2296-2306
47. Soukupova D., Dostal M., and Piza J. Developmental toxicity of cadmium in mice. II. Immunotoxic effects. Funct. Dev. Morphol. 1 (1991) 31-36
48. Staal F.J., Noort Mv M., Strous G.J., and Clevers H.C. Wnt signals are transmitted through N-terminally dephosphorylated beta-catenin. EMBO Rep. 3 (2002) 63-68
49. Stone D.M., Hynes M., Armanini M., Swanson T.A., Gu Q., Johnson R.L., Scott M.P., Pennica D., Goddard A., Phillips H., Noll M., Hooper J.E., de Sauvage F., and Rosenthal A. The tumour-suppressor gene patched encodes a candidate receptor for sonic hedgehog. Nature 384 (1996) 129-134
50. Taipale J., Cooper M.K., Maiti T., and Beachy P.A. Patched acts catalytically to suppress the activity of Smoothened. Nature 418 (2002) 892-897
51. Tanaka K., Okabayashi K., Asashima M., Perrimon N., and Kadowaki T. The evolutionarily conserved porcupine gene family is involved in the processing of the Wnt family. Eur. J. Biochem. 267 (2000) 4300-4311
52. Tang N., and Enger M.D. Cd(2+)-induced c-myc mRNA accumulation in NRK-49F cells is blocked by the protein kinase inhibitor H7 but not by HA1004, indicating that protein kinase C is a mediator of the response. Toxicology 81 (1993) 155-164
53. Thevenod F., Wolff N.A., Bork U., Lee W.K., and Abouhamed M. Cadmium induces nuclear translocation of beta-catenin and increases expression of c-myc and Abcb1a in kidney proximal tubule cells. Biometals 20 (2007) 807-820
54. Thijssen S., Maringwa J., Faes C., Lambrichts I., and Van Kerkhove E. Chronic exposure of mice to environmentally relevant, low doses of cadmium leads to early renal damage, not predicted by blood or urine cadmium levels. Toxicology 229 (2007) 145-156
55. Thompson J., Wong L., Lau P.S., and Bannigan J. Adherens junction breakdown in the periderm following cadmium administration in the chick embryo: distribution of cadherins and associated molecules. Reprod. Toxicol. 25 (2008) 39-46
56. Van Den Berg D.J., Sharma A.K., Bruno E., and Hoffman R. Role of members of the Wnt gene family in human hematopoiesis. Blood 92 (1998) 3189-3202
57. van den Heuvel M., and Ingham P.W. Smoothened encodes a receptor-like serpentine protein required for hedgehog signalling. Nature 382 (1996) 547-551
58. Verbeek S., Izon D., Hofhuis F., Robanus-Maandag E., te Riele H., van de Wetering M., Oosterwegel M., Wilson A., MacDonald H.R., and Clevers H. An HMG-box-containing T-cell factor required for thymocyte differentiation. Nature 374 (1995) 70-74
59. Vogt P.K., and Bos T.J. The oncogene jun and nuclear signalling. Trends Biochem. Sci. 14 (1989) 172-175
60. Wang Z., and Templeton D.M. Induction of c-fos proto-oncogene in mesangial cells by cadmium. J. Biol. Chem. 273 (1998) 73-79
61. Webb M. Persistence of stored Cd2+ in the livers and kidneys of female rats during pregnancy. J. Reprod. Fertil. 30 (1972) 99-103
62. Willert K., Brown J.D., Danenberg E., Duncan A.W., Weissman I.L., Reya T., Yates III J.R., and Nusse R. Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature 423 (2003) 448-452
63. Xiao S., Li Y., and Chen W. Kinetics of thymocyte developmental process in fetal and neonatal mice. Cell Research 13 (2003) 265-273
64. Yu R.M., Lin C.C., Chan P.K., Chow E.S., Murphy M.B., Chan B.P., Muller F., Strahle U., and Cheng S.H. Four-dimensional imaging and quantification of gene expression in early developing zebrafish (Danio rerio) embryos. Toxicol. Sci. 90 (2006) 529-538
65. Zeng X., Goetz J.A., Suber L.M., Scott Jr. W.J., Schreiner C.M., and Robbins D.J. A freely diffusible form of sonic hedgehog mediates long-range signalling. Nature 411 (2001) 716-720
66. Zhai L., Chaturvedi D., and Cumberledge S. Drosophila wnt-1 undergoes a hydrophobic modification and is targeted to lipid rafts, a process that requires porcupine. J. Biol. Chem. 279 (2004) 33220-33227