Endoplasmic reticulum chaperones inhibit the production of amyloid-β peptides

Biochemical Journal - Tập 402 Số 3 - Trang 581-589 - 2007
Tatsuya Hoshino1, Tadashi Nakaya2, Wataru Araki3, Keitarou Suzuki1, Toshiharu Suzuki2, Tohru Mizushima1
1Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan
2Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
3Department of Demyelinating Disease and Ageing, National Institute of Neuroscience, Kodaira 187-8502, Japan

Tóm tắt

Aβ (amyloid-β peptides) generated by proteolysis of APP (β-amyloid precursor protein), play an important role in the pathogenesis of AD (Alzheimer's disease). ER (endoplasmic reticulum) chaperones, such as GRP78 (glucose-regulated protein 78), make a major contribution to protein quality control in the ER. In the present study, we examined the effect of overexpression of various ER chaperones on the production of Aβ in cultured cells, which produce a mutant type of APP (APPsw). Overexpression of GRP78 or inhibition of its basal expression, decreased and increased respectively the level of Aβ40 and Aβ42 in conditioned medium. Co-expression of GRP78's co-chaperones ERdj3 or ERdj4 stimulated this inhibitory effect of GRP78. In the case of the other ER chaperones, overexpression of some (150 kDa oxygen-regulated protein and calnexin) but not others (GRP94 and calreticulin) suppressed the production of Aβ. These results indicate that certain ER chaperones are effective suppressors of Aβ production and that non-toxic inducers of ER chaperones may be therapeutically beneficial for AD treatment. GRP78 was co-immunoprecipitated with APP and overexpression of GRP78 inhibited the maturation of APP, suggesting that GRP78 binds directly to APP and inhibits its maturation, resulting in suppression of the proteolysis of APP. On the other hand, overproduction of APPsw or addition of synthetic Aβ42 caused up-regulation of the mRNA of various ER chaperones in cells. Furthermore, in the cortex and hippocampus of transgenic mice expressing APPsw, the mRNA of some ER chaperones was up-regulated in comparison with wild-type mice. We consider that this up-regulation is a cellular protective response against Aβ.

Từ khóa


Tài liệu tham khảo

Hardy, 2002, The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics, Science, 297, 353, 10.1126/science.1072994

Mattson, 2004, Pathways towards and away from Alzheimer's disease, Nature, 430, 631, 10.1038/nature02621

Sisodia, 2002, γ-Secretase, Notch, Aβ and Alzheimer's disease: where do the presenilins fit in?, Nat. Rev. Neurosci., 3, 281, 10.1038/nrn785

Selkoe, 1999, Translating cell biology into therapeutic advances in Alzheimer's disease, Nature, 399, A23, 10.1038/399a023

Haass, 2004, Take five–BACE and the γ-secretase quartet conduct Alzheimer's amyloid β-peptide generation, EMBO J., 23, 483, 10.1038/sj.emboj.7600061

Price, 1998, Genetic neurodegenerative diseases: the human illness and transgenic models, Science, 282, 1079, 10.1126/science.282.5391.1079

Mattson, 2001, Perturbed endoplasmic reticulum function, synaptic apoptosis and the pathogenesis of Alzheimer's disease, Biochem. Soc. Symp., 67, 151, 10.1042/bss0670151

Yan, 1997, An intracellular protein that binds amyloid-β peptide and mediates neurotoxicity in Alzheimer's disease, Nature, 389, 689, 10.1038/39522

Kaufman, 2002, Orchestrating the unfolded protein response in health and disease, J. Clin. Invest., 110, 1389, 10.1172/JCI0216886

Ron, 2002, Translational control in the endoplasmic reticulum stress response, J. Clin. Invest., 110, 1383, 10.1172/JCI0216784

Yoshida, 2000, ATF6 activated by proteolysis binds in the presence of NF-Y (CBF) directly to the cis-acting element responsible for the mammalian unfolded protein response, Mol. Cell Biol., 20, 6755, 10.1128/MCB.20.18.6755-6767.2000

Luo, 2003, Induction of Grp78/BiP by translational block: activation of the Grp78 promoter by ATF4 through and upstream ATF/CRE site independent of the endoplasmic reticulum stress elements, J. Biol. Chem., 278, 37375, 10.1074/jbc.M303619200

Harding, 2000, Regulated translation initiation controls stress-induced gene expression in mammalian cells, Mol. Cell, 6, 1099, 10.1016/S1097-2765(00)00108-8

Katayama, 2001, Disturbed activation of endoplasmic reticulum stress transducers by familial Alzheimer's disease-linked presenilin-1 mutations, J. Biol. Chem., 276, 43446, 10.1074/jbc.M104096200

Niwa, 1999, A role for presenilin-1 in nuclear accumulation of Ire1 fragments and induction of the mammalian unfolded protein response, Cell, 99, 691, 10.1016/S0092-8674(00)81667-0

Guo, 1999, Increased vulnerability of hippocampal neurons to excitotoxic necrosis in presenilin-1 mutant knock-in mice, Nat. Med., 5, 101, 10.1038/4789

Katayama, 2004, Induction of neuronal death by ER stress in Alzheimer's disease, J. Chem. Neuroanat., 28, 67, 10.1016/j.jchemneu.2003.12.004

Sato, 2001, Increased production of β-amyloid and vulnerability to endoplasmic reticulum stress by an aberrant spliced form of presenilin 2, J. Biol. Chem., 276, 2108, 10.1074/jbc.M006886200

Lee, 2001, The glucose-regulated proteins: stress induction and clinical applications, Trends. Biochem. Sci., 26, 504, 10.1016/S0968-0004(01)01908-9

Tamatani, 2001, ORP150 protects against hypoxia/ischemia-induced neuronal death, Nat. Med., 7, 317, 10.1038/85463

Ellgaard, 2001, ER quality control: towards an understanding at the molecular level, Curr. Opin. Cell Biol., 13, 431, 10.1016/S0955-0674(00)00233-7

Yang, 1998, The chaperone BiP/GRP78 binds to amyloid precursor protein and decreases Aβ40 and Aβ42 secretion, J. Biol. Chem., 273, 25552, 10.1074/jbc.273.40.25552

Vattemi, 2004, Endoplasmic reticulum stress and unfolded protein response in inclusion body myositis muscle, Am. J. Pathol., 164, 1, 10.1016/S0002-9440(10)63089-1

Kakimura, 2002, Possible involvement of ER chaperone Grp78 on reduced formation of amyloid-β deposits, Ann. N.Y. Acad. Sci., 977, 327, 10.1111/j.1749-6632.2002.tb04834.x

Hoozemans, 2005, The unfolded protein response is activated in Alzheimer's disease, Acta Neuropathol., 110, 165, 10.1007/s00401-005-1038-0

Yoo, 2001, Deranged expression of molecular chaperones in brains of patients with Alzheimer's disease, Biochem. Biophys. Res. Commun., 280, 249, 10.1006/bbrc.2000.4109

Takeda, 2004, Enhanced generation of intracellular Aβ42 amyloid peptide by mutation of presenilins PS1 and PS2, Eur. J. Neurosci., 19, 258, 10.1111/j.0953-816X.2003.03135.x

Hoshino, 2003, Prostaglandin E2 protects gastric mucosal cells from apoptosis via EP2 and EP4 receptor activation, J. Biol. Chem., 278, 12752, 10.1074/jbc.M212097200

Gu, 2001, Distinct intramembrane cleavage of the β-amyloid precursor protein family resembling γ-secretase-like cleavage of Notch, J. Biol. Chem., 276, 35235, 10.1074/jbc.C100357200

Tomita, 1998, A basic amino acid in the cytoplasmic domain of Alzheimer's β-amyloid precursor protein (APP) is essential for cleavage of APP at the α-site, J. Biol. Chem., 273, 19304, 10.1074/jbc.273.30.19304

Taru, 2004, Facilitation of stress-induced phosphorylation of β-amyloid precursor protein family members by X11-like/Mint2 protein, J. Biol. Chem., 279, 21628, 10.1074/jbc.M312007200

Forman, 1997, Differential effects of the swedish mutant amyloid precursor protein on β-amyloid accumulation and secretion in neurons and nonneuronal cells, J. Biol. Chem., 272, 32247, 10.1074/jbc.272.51.32247

Landry, 2003, Structure and energetics of an allele-specific genetic interaction between dnaJ and dnaK: correlation of nuclear magnetic resonance chemical shift perturbations in the J-domain of Hsp40/DnaJ with binding affinity for the ATPase domain of Hsp70/DnaK, Biochemistry., 42, 4926, 10.1021/bi027070y

Yu, 2000, HEDJ, an Hsp40 co-chaperone localized to the endoplasmic reticulum of human cells, J. Biol. Chem., 275, 24984, 10.1074/jbc.M000739200

Shen, 2002, Identification and characterization of a novel endoplasmic reticulum (ER) DnaJ homologue, which stimulates ATPase activity of BiP in vitro and is induced by ER stress, J. Biol. Chem., 277, 15947, 10.1074/jbc.M112214200

Tomita, 1998, Cleavage of Alzheimer's amyloid precursor protein (APP) by secretases occurs after O-glycosylation of APP in the protein secretory pathway. Identification of intracellular compartments in which APP cleavage occurs without using toxic agents that interfere with protein metabolism, J. Biol. Chem., 273, 6277, 10.1074/jbc.273.11.6277

Stadelmann, 1999, Activation of caspase-3 in single neurons and autophagic granules of granulovacuolar degeneration in Alzheimer's disease. Evidence for apoptotic cell death, Am. J. Pathol., 155, 1459, 10.1016/S0002-9440(10)65460-0

Games, 1995, Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein, Nature, 373, 523, 10.1038/373523a0

Sturchler-Pierrat, 1997, Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology, Proc. Natl. Acad. Sci. U.S.A., 94, 13287, 10.1073/pnas.94.24.13287

Van Dam, 2003, Age-dependent cognitive decline in the APP23 model precedes amyloid deposition, Eur. J. Neurosci., 17, 388, 10.1046/j.1460-9568.2003.02444.x

Oda, 2003, EDEM as an acceptor of terminally misfolded glycoproteins released from calnexin, Science, 299, 1394, 10.1126/science.1079181

Zhang, 2002, Selective cytotoxicity of intracellular amyloid β peptide1−42 through p53 and Bax in cultured primary human neurons, J. Cell. Biol., 156, 519, 10.1083/jcb.200110119

Kadowaki, 2005, Amyloid β induces neuronal cell death through ROS-mediated ASK1 activation, Cell Death Differ., 12, 19, 10.1038/sj.cdd.4401528

Wooden, 1991, Transactivation of the grp78 promoter by malfolded proteins, glycosylation block, and calcium ionophore is mediated through a proximal region containing a CCAAT motif which interacts with CTF/NF-I, Mol. Cell Biol., 11, 5612

Drummond, 1987, Depletion of intracellular calcium stores by calcium ionophore A23187 induces the genes for glucose-regulated proteins in hamster fibroblasts, J. Biol. Chem., 262, 12801, 10.1016/S0021-9258(18)45277-5

Ferreiro, 2004, Involvement of endoplasmic reticulum Ca2+ release through ryanodine and inositol 1,4,5-triphosphate receptors in the neurotoxic effects induced by the amyloid-β peptide, J. Neurosci. Res., 76, 872, 10.1002/jnr.20135

Demuro, 2005, Calcium dysregulation and membrane disruption as a ubiquitous neurotoxic mechanism of soluble amyloid oligomers, J. Biol. Chem., 280, 17294, 10.1074/jbc.M500997200

Cao, 2001, A transcriptionally [correction of transcriptively] active complex of APP with Fe65 and histone acetyltransferase Tip60, Science, 293, 115, 10.1126/science.1058783

Hartmann, 1999, Intracellular biology of Alzheimer's disease amyloid β peptide, Eur. Arch. Psychiatry Clin. Neurosci., 249, 291, 10.1007/s004060050102

Kudo, 2006, Altered localization of amyloid precursor protein under endoplasmic reticulum stress, Biochem. Biophys. Res. Commun., 344, 525, 10.1016/j.bbrc.2006.03.173