Skip to main content
Log in

The normal cellular prion protein (PrPc) is strongly expressed in bovine endocrine pancreas

  • Original paper
  • Published:
Histochemistry and Cell Biology Aims and scope Submit manuscript

Summary

Expression of the cellular prion protein (PrPc) has been shown to be crucial for the development of transmissible spongiform encephalopathies and for the accumulation of the disease-associated conformer (PrPsc) in the brain and other tissues. One of the emerging hypotheses is that the conversion phenomenon could take place at the site where the infectious agent meets PrPc. In this work we have studied whether PrPc, a protein found predominantly in neurons, could also exist in pancreatic endocrine cells since neuroectoderm-derived cells and pancreatic islet cells share a large number of similarities. For this purpose we have examined the expression of PrPc in a series of fetal and postnatal bovine pancreatic tissue by immunohistochemistry and RT-PCR. Using immunostained serial sections and specific antibodies against bovine PrPc, insulin, glucagon, somatostatin, chromogranin A and chromogranin B we found that PrPc is highly expressed in all endocrine cells of fetal and adult pancreatic islets with a particular strong expression in A-cells. Moreover it became evident that the PrPc gene-neighbour chromogranin B as well as chromogranin A are coexpressed together with PrPc. The selective expression of PrPc in the bovine endocrine pancreas is of particular importance regarding possible iatrogenic transmission routes and demonstrates also that bovine pancreatic islet cells could represent an interesting model to study the control of PrP-gene expression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Aguzzi A, Heppner FL, Heikenwalder M, Prinz M, Mertz K, Seeger H, Glatzel M (2003) Immune system and peripheral nerves in propagation of prions to CNS. Br Med Bull 66:141–156

    Article  PubMed  CAS  Google Scholar 

  • Aguzzi A, Weissmann C (1997) Prion research: the next frontiers. Nature 389:795–798

    Article  PubMed  CAS  Google Scholar 

  • Andreoletti O, Berthon P, Marc D, Sarradin P, Grosclaude J, van Keulen L, Schelcher F, Elsen JM, Lantier F (2000) Early accumulation of PrPSc in gut-associated lymphoid and nervous tissues of susceptible sheep from a Romanov flock with natural scrapie. J Gen Virol 81:3115–3126

    PubMed  CAS  Google Scholar 

  • Atouf F, Scharfmann R, Lasmezas C, Czernichow P (1994) Tight hormonal control of PrP gene expression in endocrine pancreatic cells. Biochem Biophys Res Commun 201:1220–1226

    Article  PubMed  CAS  Google Scholar 

  • Baron TGM, Madec JY, Calavas D (1999) Similar signature of the prion protein in natural sheep scrapie and bovine spongiform encephalopathy-linked diseases. J Clin Microbiol 37:3701–3704

    PubMed  CAS  Google Scholar 

  • Borelli MI, Villar MJ, Orezzoli A, Gagliardino JJ (1997) Presence of DOPA decarboxylase and its localisation in adult rat pancreatic islet cells. Diabetes Metabol 23:161–163

    CAS  Google Scholar 

  • Bounias M, Purdey M (2002) Transmissible spongiform encephalopathies: a family of etiologically complex diseases–a review. Sci Total Environ 297:1–19

    Article  PubMed  CAS  Google Scholar 

  • Brandner S, Klein MA, Frigg R, Pekarik V, Parizek P, Raeber A, Glatzel M, Schwarz P, Rulicke T, Weissmann C, Aguzzi A (2000) Neuroinvasion of prions: insights from mouse models. Exp Physiol 85:705–712

    Article  PubMed  CAS  Google Scholar 

  • Brini M (2003) Ca(2+) signalling in mitochondria: mechanism and role in physiology and pathology. Cell Calcium 34:399d–405

    Article  CAS  Google Scholar 

  • Brini M, Miuzzo M, Pierobon N, Negro A, Sorgato MC (2005) The prion protein and its paralogue doppel affect calcium signaling in Chinese hamster ovary (CHO) cells. Mol Biol Cell 10:2799–2808

    Article  CAS  Google Scholar 

  • Brown DR (2001) Copper and prion disease. Brain Res Bull 55:165–173

    Article  PubMed  CAS  Google Scholar 

  • Brown DR, Qin KF, Herms JW, Madlung A, Manson J, Strome R, Fraser PE, Kruck T, vonBohlen A, SchulzSchaeffer W, Giese A, Westaway D, Kretzschmar H (1997) The cellular prion protein binds copper in vivo. Nature 390:684–687

    Article  PubMed  CAS  Google Scholar 

  • Brown KL, Ritchie DL, Mcbride PA, Bruce ME (2000) Detection of PrP in extraneural tissues. Microsc Res Techn 50:40–45

    Article  CAS  Google Scholar 

  • Burthem J, Urban B, Pain A, Roberts DJ (2001) The normal cellular prion protein is strongly expressed by myeloid dendritic cells. Blood 98:3733–3738

    Article  PubMed  CAS  Google Scholar 

  • Cetin Y, Aunis D, Bader MF, Galindo E, Jorns A, Bargsten G, Grube D (1993) Chromostatin, A Chromogranin-A-derived bioactive peptide, is present in human pancreatic insulin (beta) cells. Proc Natl Acad Sci USA 90:2360–2364

    Article  PubMed  CAS  Google Scholar 

  • Choe CU, Harrison KD, Grant W, Ehrlich BE (2004) Functional coupling of chromogranin with the inositol 1,4,5-trisphosphate receptor shapes calcium signaling. J Biol Chem 279:35551–35556

    Article  PubMed  CAS  Google Scholar 

  • Cirulli V, Baetens D, Rutishauser U, Halban PA, Orci L, Rouiller DG (1994) Expression of neural cell-adhesion molecule (N-Cam) in rat islets and its role in islet-cell type segregation. J Cell Sci 107:1429–1436

    PubMed  CAS  Google Scholar 

  • Colling SB, Khana M, Collinge J, Jefferys JGR (1997) Mossy fibre reorganization in the hippocampus of prion protein null mice. Brain Res 755:28–35

    Article  PubMed  CAS  Google Scholar 

  • De Camilli P, Jahn R (1990) Pathways to regulated exocytosis in neurons. Annu Rev Physiol 52:625–645

    Article  PubMed  Google Scholar 

  • DeArmond SJ, Qiu Y, Sanchez H, Spilman PR, Ninchak-Casey A, Alonso D, Daggett V (1999) PrPC glycoform heterogeneity as a function of brain region: implications for selective targeting of neurons by prion strains. J Neuropathol Exp Neurol 58:1000–1009

    Article  PubMed  CAS  Google Scholar 

  • Evans HE, Sack WO (1973) Prenatal development of domestic and laboratory mammals: growth curves, external features and selected references. Zentralbl Veterinarmed [C] 2:11–45

    CAS  Google Scholar 

  • EMEA/ 410/01 Rev. 2 (2004) Official Journal of the European Union. C24/6

  • Farquhar CF, Dornan J, Somerville RA, Tunstall AM, Hope J (1994) Effect of sinc genotype, agent isolate and route of infection on the accumulation of protease-resistant prp in noncentral nervous-system tissues during the development of murine scrapie. J Gen Virol 75:495–504

    PubMed  CAS  Google Scholar 

  • Filiz S, Dalcik H, Yardimoglu M, Gonca S, Ceylan S (2002) Localization of neural cell adhesion molecule (N-CAM) immunoreactivity in adult rat tissues. Biotechn Histochem 77:127–135

    Article  CAS  Google Scholar 

  • Ford M, Li H, Burton L, Jen A, Morris R, Hall S (2000) Cellular prion protein expression in the mouse. Eur J Neurosci 12:116

    Google Scholar 

  • Fournier JG, Escaig-Haye F, de Villemeur TB, Robain O, Lasmezas CI, Deslys JP, Dormont D, Brown P (1998) Distribution and submicroscopic immunogold localization of cellular prion protein (PrPc) in extracerebral tissues. Cell Tissue Res 292:77–84

    Article  PubMed  CAS  Google Scholar 

  • Gauczynski S, Peyrin JM, Haik S, Leucht C, Hundt C, Rieger R, Krasemann S, Deslys JP, Dormont D, Lasmezas CI, Weiss S (2001) The 37-kDa/67-kDa laminin receptor acts as the cell-surface receptor for the cellular prion protein. EMBO J 20:5863–5875

    Article  PubMed  CAS  Google Scholar 

  • Harmeyer S, Pfaff E, Groschup MH (1998) Synthetic peptide vaccines yield monoclonal antibodies to cellular and pathological prion proteins of ruminants. J Gen Virol 79:937–945

    PubMed  CAS  Google Scholar 

  • Herms JW, Korte S, Gall S, Schneider I, Dunker S, Kretzschmar HA (2000) Altered intracellular calcium homeostasis in cerebellar granule cells of prion protein-deficient mice. J Neurochem 75:1487–1492

    Article  PubMed  CAS  Google Scholar 

  • Herms JW, Tings T, Dunker S, Kretzschmar HA (2001) Prion protein affects Ca2+-activated K+ currents in cerebellar purkinje cells. Neurobiol Dis 8:324–330

    Article  PubMed  CAS  Google Scholar 

  • Hetz C, Maundrell K, Soto C (2003a) Is loss of function of the prion protein the cause of prion disorders? Trends Mol Med 9:237–243

    Article  PubMed  CAS  Google Scholar 

  • Hetz C, Russelakis-Carneiro M, Maundrell K, Castilla J, Soto C (2003b) Caspase-12 and endoplasmic reticulum stress mediate neurotoxicity of pathological prion protein. Embo J 22:5435–5445

    Article  PubMed  CAS  Google Scholar 

  • Horiuchi M, Yamazaki N, Ikeda T, Ishiguro N, Shinagawa M (1995) A cellular-form of prion protein (prpc) exists in many nonneuronal tissues of sheep. J Gen Virol 76:2583–2587

    PubMed  CAS  Google Scholar 

  • Huang FP, Farquhar CF, Mabbott NA, Bruce ME, MacPherson GG (2002) Migrating intestinal dendritic cells transport PrPsc from the gut. J Gen Virol 83:267–271

    PubMed  CAS  Google Scholar 

  • Jackson GS, Clarke AR (2000) Mammalian prion proteins. Curr Opin Struct Biol 10:69–74

    Article  PubMed  CAS  Google Scholar 

  • Kawahara M, Kuroda Y, Arispe N, Rojas E (2000) Alzheimer’s beta-amyloid, human islet amylin, and prion protein fragment evoke intracellular free calcium elevations by a common mechanism in a hypothalamic GnRH neuronal cell line. J Biol Chem 275:14077–14083

    Article  PubMed  CAS  Google Scholar 

  • Lezmi S, Bencsik A, Monks E, Petit T, Baron T (2003) First case of feline spongiform encephalopathy in a captive cheetah born in France: PrPsc analysis in various tissues revealed unexpected targeting of kidney and adrenal gland. Histochem Cell Biol 119:415–422

    PubMed  CAS  Google Scholar 

  • Lucini C, Costagliola C, Borzacchiello G, Castaldo L (2003) Neurotrophin 3 and its receptor TrkC immunoreactivity in glucagon cells of buffalo pancreas. Anat Histol Embryol J Vet Med Ser C 32:253–256

    Article  CAS  Google Scholar 

  • Lukinius A, Stridsberg M, Wilander E (2003) Cellular expression and specific intragranular localization of chromogranin A, chromogranin B, and synaptophysin during ontogeny of pancreatic islet cells: an ultrastructural study. Pancreas 27:38–46

    Article  PubMed  CAS  Google Scholar 

  • Mabbott NA, Brown KL, Manson J, Bruce ME (1997) T-lymphocyte activation and the cellular form of the prion protein. Immunology 92:161–165

    Article  PubMed  CAS  Google Scholar 

  • Mabbott NA, Farquhar CF, Brown KL, Bruce ME (1998) Involvement of the immune system in TSE pathogenesis. Immunol Today 19:201–203

    Article  PubMed  CAS  Google Scholar 

  • Madec JY, Groschup MH, Calavas D, Junghans F, Baron T (2000) Protease-resistant prion protein in brain and lymphoid organs of sheep within a naturally scrapie-infected flock. Microbial Pathogen 28:353–362

    Article  CAS  Google Scholar 

  • Martins VR, Graner E, Garcia-Abreu J, de Souza SJ, Mercadante AF, Veiga SS, Zanata SM, Neto VM, Brentani RR (1997) Complementary hydropathy identifies a cellular prion protein receptor. Nat Med 3:1376–1382

    Article  PubMed  CAS  Google Scholar 

  • Mattson MP, Goodman Y (1995) Different amyloidogenic peptides share a similar mechanism of neurotoxicity involving reactive oxygen species and calcium. Brain Res 676:219–224

    Article  PubMed  CAS  Google Scholar 

  • McBride PA, Eikelenboom P, Kraal G, Fraser H, Bruce ME (1992) PrP protein is associated with follicular dendritic cells of spleens and lymph nodes in uninfected and scrapie-infected mice. J Pathol 168:413–418

    Article  PubMed  CAS  Google Scholar 

  • Miknyoczki SJ, Lang D, Huang LY, Klein-Szanto AJP, Dionne CA, Ruggeri BA (1999) Neurotrophins and Trk receptors in human pancreatic ductal adenocarcinoma: Expression patterns and effects on in vitro invasive behavior. Int J Cancer 81:417–427

    Article  PubMed  CAS  Google Scholar 

  • Mulder H, Myrsen-Axcrona U, Gebre-Medhin S, Ekblad E, Sundler F (1998) Expression of non-classical islet hormone-like peptides during the embryonic development of the pancreas. Microsc Res Techn 43:313–321

    Article  CAS  Google Scholar 

  • Ohta T, Numata M, Tsukioka Y, Futagami F, Kayahara M, Kitagawa H, Nagakawa T, Yamamoto M, Wakayama T, Kitamura Y, Nakanuma Y (1997) Neurotrophin-3 expression in human pancreatic cancers. J Pathol 181:405–412

    Article  PubMed  CAS  Google Scholar 

  • Pammer J, Cross HS, Frobert Y, Tschachler E, Oberhuber G (2000) The pattern of prion-related protein expression in the gastrointestinal tract. Virchows Archiv Int J Pathol 436:466–472

    Article  CAS  Google Scholar 

  • Pammer J, Weninger W, Tschachler E (1999) Expression of cellular prion-related-protein by human and bovine keratinocytes in situ and in vitro. J Investig Dermatol 112:651

    Google Scholar 

  • Persson-Sjogren S, Forsgren S, Taljedal IB (2002) Tyrosine hydroxylase in mouse pancreatic islet cells, in situ and after syngeneic transplantation to kidney. Histol Histopathol 17:113–121

    PubMed  CAS  Google Scholar 

  • Peters J, Miller JM, Jenny AL, Peterson TL, Carmichael KP (2000) Immunohistochemical diagnosis of chronic wasting disease in preclinically affected elk from a captive herd. J Vet Diagn Investig 12:579–582

    CAS  Google Scholar 

  • Prinz M, Montrasio F, Klein MA, Schwarz P, Priller J, Odermatt B, Pfeffer K, Aguzzi A (2002) Lymph nodal prion replication and neuroinvasion in mice devoid of follicular dendritic cells. PNAS 99: 919–924

    Article  PubMed  CAS  Google Scholar 

  • Prusiner SB (1998) The prion diseases. Brain Pathol 8:499–513

    Article  PubMed  CAS  Google Scholar 

  • Rangon CM, Haik S, Faucheux BA, Metz-Boutigue MH, Fierville F, Fuchs JP, Hauw JJ, Aunis D (2003) Different chromogranin immunoreactivity between prion and a-beta amyloid plaque. Neuroreport 14:755–758

    Article  PubMed  CAS  Google Scholar 

  • Rieger R, Edenhofer F, Lasmezas CI, Weiss S (1997) The human 37-kDa laminin receptor precursor interacts with the prion protein in eukaryotic cells. Nat Med 3:1383–1388

    Article  PubMed  CAS  Google Scholar 

  • Saito M, Sugiyama K (2000) A distinct ganglioside composition of rat pancreatic islets. Arch Biochem Biophys 376:371–376

    Article  PubMed  CAS  Google Scholar 

  • Sakaguchi S, Katamine S, Nishida N, Moriuchi R, Shigematsu K, Sugimoto T, Nakatani A, Kataoka Y, Houtani T, Shirabe S, Okada H, Hasegawa S, Miyamoto T, Noda T (1996) Loss of cerebellar Purkinje cells in aged mice homozygous for a disrupted PrP gene. Nature 380:528–531

    Article  PubMed  CAS  Google Scholar 

  • Sigurdson CJ, Spraker TR, Miller MW, Oesch B, Hoover EA (2001) PrP (CWD) in the myenteric plexus, vagosympathetic trunk and endocrine glands of deer with chronic wasting disease. J Gen Virol 82:2327–2334

    PubMed  CAS  Google Scholar 

  • Singh N, Zanusso G, Chen SG, Fujioka H, Richardson S, Gambetti P, Petersen RB (1997) Prion protein aggregation reverted by low temperature in transfected cells carrying a prion protein gene mutation. J Biol Chem 272:28461–28470

    Article  PubMed  CAS  Google Scholar 

  • Takayanagi M, Watanabe T (1996) Immunocytochemical colocalizations of insulin, aromatic L-amino acid decarboxylase, dopamine beta-hydroxylase, S-100 protein and chromogranin A in B-cells of the chicken endocrine pancreas. Tissue Cell 28:17–24

    Article  PubMed  CAS  Google Scholar 

  • Thrower EC, Choe CU, So SH, Jeon SH, Ehrlich BE, Yoo SH (2003) A functional interaction between chromogranin B and the inositol 1,4,5-trisphosphate receptor/Ca2+ channel. J Biol Chem 278:49699–49706

    Article  PubMed  CAS  Google Scholar 

  • Thrower EC, Park HY, So SH, Yoo SH, Ehrlich BE (2002) Activation of the inositol 1,4,5-trisphosphate receptor by the calcium storage protein chromogranin A. J Biol Chem 277:15801–15806

    Article  PubMed  CAS  Google Scholar 

  • Tobler I, Deboer T, Fischer M (1997) Sleep and sleep regulation in normal and prion protein-deficient mice. J Neurosci 17:1869–1879

    PubMed  CAS  Google Scholar 

  • Ye X, Carp RI, Kascsak RJ (1994) Histopathological changes in the islets of Langerhans in scrapie 139H-affected hamsters. J Comp Pathol 110:153–167

    Article  PubMed  CAS  Google Scholar 

  • Ye X, Scallet AC, Carp RI (1997) The 139H scrapie agent produces hypothalamic neurotoxicity and pancreatic islet histopathology: electron microscopic studies. Neurotoxicology 18:533–545

    PubMed  CAS  Google Scholar 

  • Zanusso G, Petersen RB, Jin TC, Jing Y, Kanoush R, Ferrari S, Gambetti P, Singh N (1999) Proteasomal degradation and N-terminal protease resistance of the codon 145 mutant prion protein. J Biol Chem 274:23396–23404

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

The authors thank Mrs. Müller, Mrs. Finkelde and Mrs. Holzäpfel for their excellent technical assistance. Supported by the TSE-Förderprogramm der Landesregierung Baden-Württemberg, FKZ: 729.59-4/1

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to W.M. Amselgruber.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Amselgruber, W., Büttner, M., Schlegel, T. et al. The normal cellular prion protein (PrPc) is strongly expressed in bovine endocrine pancreas. Histochem Cell Biol 125, 441–448 (2006). https://doi.org/10.1007/s00418-005-0089-6

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00418-005-0089-6

Key words

Navigation