Summary
Heat-shock proteins are proteins serving as molecular chaperones, involved in the protection of cells from various forms of stress. Since the expression of these proteins is closely related to that of amyloid precursor protein (APP), heat-shock protein has been studied in brain of patients with Alzheimer’ s disease (AD) and furthermore, brain Hsp70 mRNA levels were related to the agonal state. The aim of our study was to demonstrate the presence of Hsp70 — immunoreactive protein in brain of controls, patients with AD and Down Syndrome (DS) in individual brain regions. The rationale for the study was to test the hypothesis that expression of Hsp70, a protein involved in apoptosis would be altered in brain of these patients with neurodegenerative disorders where (neuronal) apoptosis is a hallmark of the disease. Brain immunoreactive-Hsp70 — protein (Hsp70) was determined by Western blotting using specific monoclonal antibody in five different brain regions (frontal, parietal, occipital, temporal cortex and cerebellum) from controls, DS and AD patients. Hsp70 expression was significantly increased in temporal cortex of patients with AD (arbitrary units: means ± SD; 0.35 ± 0.49 for controls, 0.97 ± 0.70 for DS patients, 1.16 ± 0.56 for AD patients). In frontal and parietal cortex from DS patients, there was a strong correlation between Hsp70 levels and the length of post-mortem interval (r = 0.95, P > 0.01 and r = 0.82, P > 0.021).
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Abe K, St. George Hyslop PH, Tanzi RE, Kogure K (1991) Induction of amyloid precursor protein mRNA after heat shock in cultured human lymphoblastoid cells. Neurosci Lett 125: 169–171
Bradford M (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248–254
Busciglio J, Yankner BA (1995) Apoptosis and increased generation of reactive oxygen species in Down’s syndrome neurons in vitro. Nature 378: 776–779
de la Monte SM, Xu YY, Wands JR (1996) Neuronal thread protein gene modulation with sprouting: relevevance to Alzheimer’s disease. J Neurol Sci 138: 26–35
de la Monte SM, Sohn YK, Wands JR (1997) Correlates of p53-and Fas (CD95)-mediated apoptosis in Alzheimer’s disease. J Neurol Sci 152: 73–83
de la Monte SM, Sohn YK, Ganju N, Wands JR (1998) p53-and CD95-associated apoptosis in neurodegenerative diseases. Lab Invest 78: 401–411
Gabriele T, Tavaria M, Kola I, Anderson RL (1996) Analysis of heat shock protein 70 in human chromosome 21 containing hybrids. Int J Biochem Cell Biol 28: 905–910
Harrison GS, Drabkin HA, Kao FT, Hart IM, Chu EH, Wu BJ, Morimoto RI (1987) Chromosomal location of human genes encoding major heat-shock protein HSP70. Somat Cell Mol Genet 13: 119–130
Harrison PJ, Procter AW, Exworthy T, Roberts GW, Najilerahim A, Barton AJ, Pearson RC (1993) Heat shock protein (hsx70) mRNA expression in human brain: effects of neurodegenerative disease and agonal state. Neuropathol Appl Neurobiol 19: 10–21
Hartl FU (1996) Molecular chaperones in cellular protein folding. Nature 381: 571–578
Johnson G, Refolo LM, Wallace W (1993) Heat-shocked neuronal PC12 cells reveal Alzheimer’s disease-associated alterations in amyloid precursor protein and tau. Ann NY Acad Sci 685: 194–197
Johnston JA, Lannfelt L, Wiehanger B, Oneill C, Cowburn RF (1997) Amyloid precursor protein heat shock response in lymphoblastoid cell lines bearing presenilin-1 mutation. Biochem Biophys Acta Molecular Basis of Disease 1362: 182–192
Kudva YC, Hiddinga HJ, Butler PC, Mueske CS, Eberhart NL (1997) Small heat shock proteins inhibit in vitro A beta (1–42) amyloidogenesis. FEBS Lett 416: 117–121
Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 277: 680–685
Leung PS, Gershwin ME (1991) The immunobiology of heat shock proteins. J Investg Allergol Clin Immunol 1: 23–30
Mirra SS, Heyman A, McKeel D, Sumi S, Crain BJ (1991) The consortium to establish a registry for Alzheimer disease (CERAD). II. Standardization of the neuropathologi-cal assessment of Alzheimer’s disease. Neurology 41: 479–486
Morimoto RI, Tissieres A, Georgopoulos (1994) The biology of heat shock proteins and molecular chaperones. Cold Spring Harbor, New York, pp 1–593
Morrison-Bogorad M, Zimmerman AL, Pardue S (1995) Heat-shock 70 messenger RNA levels in human brain: correlation with agonal fever. J Neurochem 64: 235–246
Mosser DD, Caron AW, Bourget L, Denis-Larose C, Massie B (1997) Role of the human heat shock protein hsp70 in protection against stress-induced apoptosis. Mol Cell Biol 17: 5317–5327
Myrmel T, McCully JD, Malikin L, Krukenkamp IB, Levitsky S (1994) Heat-shock protein 70 mRNA is induced by anaerobic metabolism in rat hearts. Circulation 90: 11299–305
Nunez G, Clarke MF (1994) The Bcl-2 family of proteins: regulators of cell death and survival. Trend Cell Biol 4: 399–403
Oltvai ZN, Korsmeyer SJ (1994) Checkpoints of dueling dimers foil death wishes. Cell 79: 189–192
Reed JC (1994) Bcl-2 and the regulation of programmed cell death. J Cell Biol 124: 1–6
Renkawek K, Bosman GJ, de-Jong WW (1994) Expression of small heat-shock protein hsp27 in reactive gliosis in Alzheimer disease and other types of dementia. Acta Neuropathol Berl 87: 511–519
Sawa A, Oyama F, Cairns NJ, Amano N, Matsushita M (1997) Aberrant expression of bcl-2 gene family in Down’s syndrome brains. Mol Brain Res 48: 53–59
Seidl R, Fang-Kircher S, Cairns N, Lubec G (1999) Apoptosis-associated proteins p53 and APO-1/Fas (CD95) in brains of adult patients with Down syndrome. Neurosci Lett 260: 9–12
Strasser A, Anderson RL (1995) Bcl-2 and thermotolerance cooperate in cell survival. Cell Growth Differ 6: 799–805
Tierney MC, Fisher RH, Lewis AJ, Torzitto ML, Snow WG, Reid DW, Nieuwstraaten P, Van Rooijen LAA, Derks HJGM, Van Wiijk R, Bischop A (1988) The NINCDA-ADRDA work group criteria for the clinic diagnosis of probable Alzheimer’s disease. Neurology 38: 359–364
Wakutani Y, Urakami K, Shimomura T, Takahasi K (1995) Heat shock protein 70 mRNA levels in mononuclear blood cells from patients with dementia of the Alzheimer type. Dementia 6: 301–305
Werner MH (1996) Stopping death cold. Structure 4: 879–883
Zhong S, Wu K, Black IB, Schaar DG (1996) Characterization of the genomic structure of the mouse APLP1 gene. Genetics 32: 159–162
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1999 Springer-Verlag Wien
About this paper
Cite this paper
Yoo, B.C., Seidl, R., Cairns, N., Lubec, G. (1999). Heat-shock protein 70 levels in brain of patients with Down Syndrome and Alzheimer’s disease. In: Lubec, G. (eds) The Molecular Biology of Down Syndrome. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6380-1_22
Download citation
DOI: https://doi.org/10.1007/978-3-7091-6380-1_22
Publisher Name: Springer, Vienna
Print ISBN: 978-3-211-83377-3
Online ISBN: 978-3-7091-6380-1
eBook Packages: Springer Book Archive