Summary
Seventeen intracerebral gliomas containing Rosenthal fibers (RF) were studied by an immunoperoxidase method for localization of ubiquitin (UB), glial fibrillary acidic protein (GFAP), desmin and vimentin (VIM). The majority of RF showed an immunohistochemically negative core surrounded by a ring of overlapping reactions for UB, GFAP and VIM. Many RF were entirely negative for UB and intermediate filaments (IF). Immunoelectron microscopic lozalization of UB and GFAP was performed on seven selected tumors. UB was found in all RF and on IF in the proximity of RF. GFAP reaction was localized on astrocytic IF, including those trapped within RF, and within the granular component of some RF. In contrast to the light microscopic studies, neither GFAP-nor UB-negative RF were found on immunoelectron microscopy. VIM reaction on IF and a few RF was demonstrated in one tumor processed at low temperature into Lowicryl; it was much weaker than that for GFAP. Many cells with RF contained lysosome-like inclusions with material displaying electron density similar to adjacent RF; few of these inclusions were reactive for UB. It is concluded that RF formation is associated with ubiquitination of astrocytic IF. GFAP-and VIM-immunoreactive IF and products of their disintegration contribute to RF material. It is also suggested that the lysosomal system of astrocytes partially degrades RF.
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Bendayan M, Zollinger M (1983) Ultrastructural localization of antigenetic sites on osmium-fixed tissues applying the protein A-gold technique. J Histochem Cytochem 31: 101–109
Bettica AM, Johnson AB (1990) Ultrastructural immunogold labelling of glial filaments in osmicated and unosmicated epoxy-embedded tissue. J Histochem Cytochem 38: 103–109
Borrett D, Becker LE (1985) Alexander's disease. A disease of astrocytes. Brain 108: 367–385
Brett M, Weller RO (1978) Intracellular serum proteins in cerebral gliomas and metastatic tumours. An immunoperoxidase study. Neuropathol Appl Neurobiol 4: 263–270
Ciechanover A, Finley D, Varshavsky A (1984) Ubiquitin dependence of selective protein degradation demonstrated in the mammalian cell cycle mutant s 85. Cell 37: 57–66
Davie JR, Delcuve GP, Nickel BE, Moirier R, Bailey G (1987) Reduced levels of Histones III and IIIb, and unaltered content of methylated DNA in rainbow trout hepatocellular carcinoma chromatin. Cancer Res 47: 5407–5410
Deck JHN, Eng LF, Bigbee J, Woodcock SM (1978) The role of glial fibrillary acidic protein in the diagnosis of central nervous system tumors. Acta Neuropathol (Berl) 42: 183–190
Dinda AK, Sarka C, Roy S (1990) Rosenthal fibers: an immunohistochemical, ultrastructural and immunoelectron microscopic study. Acta Neuropathol 79: 456–460
Doherty FJ, Wassell JA, Mayer RJ (1987) A putative protein sequestration site involving intermediate filaments for protein degradation by autophagy. Studies with microinjected purified glycolytic enzymes in 3T3-L1 cells. Biochem J 241: 793–800
Earl T, Mangiapane H, Billett EE, Mayer JJ (1987) A putative protein-sequestration site involving intermediate filaments for protein degradation by autophagy. Studies with transplanted Sendai-viral envelope proteins in HTC cells. Biochem J 241: 809–815
Finley D, Varshaysky A (1985) The ubiquitin system: functions and mechanisms. Trends Biochem Sci 47: 275–284
French SW, Swierenga HH, Okanoue T, Marceau N (1987) The cytoskeleton of the liver cell in health and disease. In: Farber E, Phillips MJ (eds) Pathogenesis of liver disease, IAP monograph no. 28. Williams and Wilkins, New York, pp 95–112
Gluszcz A, Giernat L, Habryka K, Alwasiak J, Lach B, Papierz (1971) Rosenthal fibers, birefringent gliofibrillary changes and intracellular homogenous conglomerates in tissue cultures of gliomas. Acta Neuropathol (Berl) 17: 54–67
Goldman JE, Corbin E (1988) Isolation of a major protein component of Rosenthal fibers. Am J Pathol 130: 569–578
Goldman JE, Iwaki T, Kume-Iwaki A, Wisniewski T, Liem RKH (1990) Expression of αB-Crystallin in CNS glia. Presented at XI International Congress of Neuropathology, Kyoto, Japan September 2–8, 1990
Gullotta F, Fliedener E (1972) Spongioblastomas, astrocytomas and Rosenthal fibers. Ultrastructural tissue culture and enzyme histochemical investigations. Acta Neuropathol (Berl) 22: 68–78
Hearn SA, Silver MM, Shouldice JA (1985) Immunoelectron microscopic labeling of immunoglobulin in plasma cells after osmium fixation and epoxy embedding. J Histochem Cytochem 33: 1212–1218
Herpers MJHM, Ramackers RCSA, Aldeweireldt J, Moesker O, Slooff J (1986) Co-expression of glial fibrillary acidic protein and vimentin-type intermediate filaments in human astrocytomas. Acta Neuropathol (Berl) 70: 333–339
Hershko A (1983) Ubiquitin: roles in protein modification and breakdown. Cell 34: 11–12
Hershko A, Ciechanover A, Heller H, Haas AL, Rose IA (1980) Proposed role of ATP in protein breakdown; conjugation of proteins with multiple chains of the early peptide of ATP-dependent proteolysis. Proc Natl. Acad Sci USA 77: 1783–1786
Horoupian DS, Kress Y, Yen SH, Gaskin F (1982) Nickel-induced changes and reappraisal of Rosenthal fibers in focal CNS lesions. J Neuropathol Exp Neurol 41: 664–675
Hsu SM, Soban E (1982) Color modification of diaminobenzidine (DAB) precipitation by metallic ions and its application for double immunohistochemistry. J Histochem Cytochem 30: 1079–1082
Hsu SM, Rhine L, Fung H (1981) Use of Avidin-biotin peroxidase complex (ABC) in immunoperoxidase techniques; a comparison between ABC and unlabelled antibody (PAP) procedures. J Histochem Cytochem 29: 577–580
Iwaki T, Kume-Iwaki A, Goldman JE (1989) Tissue distribution of Alfa-B crystallin in rat organs (abstract). J Neuropathol Exp Neurol 48: 363
Janzer RC, Friede RL (1981) Do Rosenthal fibers contain glial fibrillary acidic protein. Acta Neuropathol (Berl) 55: 75–76
Johnson AB, Bettice AM (1986) Rosenthal fibers in Alexander's disease show glial fibrillary acidic protein (GFAP) immunoreactivity with the immunogold staining method (abstract). J Neuropathol Exp Neurol 45: 349
Johnson AB, Bettice AM (1989) On-grid immunogold labelling of glial intermediate filaments in epoxy-embedded tissue. Am J Anat 185: 335–3411
Kellenbergen E, Carlemalm E, Villiger W, Roth J, Garavito RM (1980) Low-denaturation embedding for electron microscopy of thin sections. Chem. Werke Lowi, Waldkraiburg pp 1–59
Kren Y, Gaskin F, Horoupian DS, Brosnan C (1981) Nickel induction of Rosenthal fibers in rat brain. Brain Res 210: 419–425
Kume-Iwaki A, Iwaki T, Liem RKH, Goldman JE (1989) Alfa-B-Crystallin is a major component of Rosenthal Fibers (abstract). J Neuropathol Exp Neurol 48: 377
Lowe J, Blanchard A, Morrell K, Lennox G, Reynolds L, Billett M, Landon M, Mayer RJ (1988) Ubiquitin is a common factor in intermediate filament inclusion bodies of diverse type in men, including those of Parkinson's disease, Pick's disease, and Alzheimer disease, as well as Rosenthal fibers in astrocytomas, cytoplasmic bodies in muscle and Mallory bodies in alcoholic liver disease. J Pathol 155: 9–15
Lowe J, Morell K, Lennox G, Landon M, Mayer RJ (1989) Rosenthal fibres are based on the ubiquitination of glial filaments. Neuropathol Appl Neurobiol 15: 45–53
MacDowell CM (1978) Fixation and processing. In: Trump BJ, Jones RT (eds) Diagnostic electronmicroscopy, vol 1. Wiley Toronto, pp 113–166
Manetto V, Perry G, Tabaton M, Mulvihill P, Fried VA, Smith HT, Gambetti P, Autilio-Gambetti L (1988) Ubiquitin is associated with abnormal cytoplasmic filaments characteristic of neurodegenerative diseases. Proc Natl Acad Sci USA 85: 4501–4505
Manetto V, Abdul-Karim FW, Perry G, Tabaton M, Autilio-Gambetti L, Gambetti P (1989) Selective presence of ubiquitin in intracellular inclusions. Am J Pathol 134: 505–513
McManus JP, Brewer LM (1987) Isolation, localization and peptides of the oncodevelopmental calcium-binding protein, oncomodulin. Methods Enzymol 139: 156–168
Murti KG, Switzer HT, Fried VA (1988) Ubiquitin is a component of the microtubule network. Proc Natl Acad Sci USA 85: 3019–3023
Ohta M, Marceau N, Perry G, Manetto V, Gambetti P, Autilio-Gambetti L, Metuzals J, Kawahara H, Cadrin M, French SW (1988) Ubiquitin is present on cytokeratin intermediate filaments and Mallory bodies of hepatocytes. Lab Invest 59: 848–856
Raimondi AM, Mullan S, Evans GPN (1962) Human brain tumors: an electron microscopic study. J Neurosurg 19: 731–755
Rechsteiner M (1987) Ubiquitin-mediated pathways for intracellular proteolysis. Annu Rev Cell Biol 3: 1–30
Scopsi L, Larsson L (1986) Increased sensitivity in peroxidase immunocytochemistry. A comparative study of a number of peroxidase visualization methods employing a model system. Histochemistry 84: 221–230
Silver MM, Hearn SA (1987) Postembedding immunoelectron microscopy using protein A-gold. Ultrastruct Pathol 11: 693–703
Smith DA, Lantos PL (1985) Immunocytochemistry of cerebellar astrocytomas: with special note on Rosenthal fibers. Acta Neuropathol (Berl) 66: 155–159
Sternberger LA (1979) Immunohistochemistry, 2nd edn. John Wiley and Sons, New York, pp 104–169
Towbin HT, Staehelin T, Gordon J (1979) Electrophoretic transfer of proteins from polyacrylamide gels to nitorcellulose sheets: procedure and some applications. Proc Natl Acad Sci USA 76: 4350–4354
Traub P (1985) Intermediate filaments. A review. Springer-Verlag, Berlin, pp 14, 41, 127–129
Van der Meulen JDM, Houthoff HJ, Ebels EJ (1978) Glial fibrillary acidic protein in human gliomas. Neuropathol Appl Neurobiol 4: 177–190
Velasco ME, Dahl D, Roessmann U, Gambetti P (1980) Immunohistochemical localization of glial fibrillary acidic protein in human glial neoplasms. Cancer 45: 484–494
Wilkinson KD, Urban MK, Haas AL (1980) Ubiquitin is the ATP-dependent protolysis factor I of rabbit reticulocytes. J Biochem 225: 7529–7532
Wisniewski T, Iwaki T, Goldman JE (1990) Subcellular localization of α-crystallin B chain in CNS glia (abstract). J Neuropathol Exp Neurol 49: 344
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Lach, B., Sikorska, M., Rippstein, P. et al. Immunoelectron microscopy of Rosenthal fibers. Acta Neuropathol 81, 503–509 (1991). https://doi.org/10.1007/BF00310130
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DOI: https://doi.org/10.1007/BF00310130