Enhancement of stress-induced synthesis of hsp27 and αB crystallin by modulators of the arachidonic acid cascade

Ito, Hidenori; Hasegawa, Kaori; Inaguma, Yutaka; Kozawa, Osamu; Kato, Kanefusa

doi:10.1002/(sici)1097-4652(199602)166:2<332::aid-jcp11>3.0.co;2-d

Cited by 27 publications

(15 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is of particular interest whether this proposed intracellular A␤ metabolism also occurs to some degree in human neurons. We speculate that the ability of some nonsteroidal anti-inflammatory drugs to inhibit A␤1-42 secretion from cultured cells (48) and to reduce plaque load in transgenic A␤ mice (49) may result from the previously demonstrated ability of these drugs to modulate cellular chaperone functions (50)(51)(52).…”

Section: Discussionmentioning

confidence: 97%

Interaction of intracellular β amyloid peptide with chaperone proteins

Fonte

Kapulkin²,

Taft³

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

199

151

View full text Add to dashboard Cite

Expression of the human β amyloid peptide (Aβ) in transgenic Caenorhabditis elegans animals can lead to the formation of intracellular immunoreactive deposits as well as the formation of intracellular amyloid. We have used this model to identify proteins that interact with intracellular Aβ in vivo . Mass spectrometry analysis of proteins that specifically coimmunoprecipitate with Aβ has identified six likely chaperone proteins: two members of the HSP70 family, three αB-crystallin-related small heat shock proteins (HSP-16s), and a putative ortholog of a mammalian small glutamine-rich tetratricopeptide repeat-containing protein proposed to regulate HSP70 function. Quantitative reverse transcription–PCR analysis shows that the small heat shock proteins are also transcriptionally induced by Aβ expression. Immunohistochemistry demonstrates that HSP-16 protein closely colocalizes with intracellular Aβ in this model. Transgenic animals expressing a nonaggregating Aβ variant, a single-chain Aβ dimer, show an altered pattern of coimmunoprecipitating proteins and an altered cellular distribution of HSP-16. Double-stranded RNA inhibition of R05F9.10, the putative C. elegans ortholog of the human small glutamine-rich tetratricopeptide-repeat-containing protein (SGT), results in suppression of toxicity associated with Aβ expression. These results suggest that chaperone function can play a role in modulating intracellular Aβ metabolism and toxicity.

show abstract

Section: Discussionmentioning

confidence: 97%

Interaction of intracellular β amyloid peptide with chaperone proteins

Fonte

Kapulkin²,

Taft³

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

199

151

View full text Add to dashboard Cite

show abstract

“…This suggests that the soluble oligomer amyloid is a potent therapeutic target for amyloid-related diseases, including DRM. Because the CryAB is present as a high molecular mass complex by self-polymerization and/or binding with other small HSP families, such as HSP25 (24) and HSP22 (18), we analyzed the interaction between the CryAB-amyloid oligomers HSP25 and HSP22. In our previous report, we presented the effects of co-transfection of the wild-type CryAB with CryAB R120G in cardiomyocytes (17).…”

Section: Resultsmentioning

confidence: 99%

“…It is known that the CryAB R120G protein, which loses its chaperon-like function (33), can also bind to a molecular partner, such as a wild-type CryAB, HSP25, and form a high molecular mass complex (24,31,32). It is known that the molecular weight of the high molecular mass complex by CryAB R120G was larger than that of the complex by the wild-type CryAB (21,31,32).…”

Section: Discussionmentioning

confidence: 99%

Interruption of CryAB-Amyloid Oligomer Formation by HSP22

Sanbe

Yamauchi

Miyamoto

et al. 2007

Journal of Biological Chemistry

View full text Add to dashboard Cite

An R120G missense mutation in ␣-B-crystallin (CryAB), a small heat-shock protein (HSP), causes a desmin-related cardiomyopathy (DRM) that is characterized by the formation of aggregates containing CryAB and desmin. The mutant CryAB protein leads to the formation of inclusion bodies, which contain amyloid oligomer intermediates (amyloid oligomer) in the cardiomyocytes. To further address the underlying mechanism(s) of amyloid oligomer formation in DRM linked to the CryAB R120G, a recombinant CryAB R120G protein was generated. The purified CryAB R120G protein can form a toxic amyloid oligomer, whereas little immunoreactivity was observed in the wild-type CryAB protein. A native PAGE showed that the oligomerized form was present in the CryAB R120G protein, whereas only a high molecular mass was detected in the wildtype CryAB. The oligomerized CryAB R120G of around 240 -480 kDa showed strong positive immunoreactivity against an anti-oligomer antibody. The CryAB R120G amyloid oligomer was unstable and easily lost its conformation by ␤-mercaptoethanol and SDS. Recombinant HSP25 or HSP22 proteins can directly interrupt oligomer formation by the CryAB R120G protein, whereas the amyloid oligomer is still present in the mixture of the wild-type CryAB and CryAB R120G proteins. This interruption by HSP25 and HSP22 was confirmed in a cardiomyocyte-based study using an adenoviral transfection system. Blockade of amyloid oligomer formation by HSP25 and HSP22 recovered the ubiquitin proteosomal activity and cellular viability. Blockade of oligomer formation by small HSP may be a new therapeutic strategy for treating DRM as well as other types of amyloid-based degenerative diseases.Many systemic and neurodegenerative disorders whose etiologies are linked to misfolded or unfolded proteins are characterized by the accumulation of intracellular or extracellular protein deposits or aggregates (1). The pathologies of these diseases are complex, and the accumulation of misfolded and unfolded proteins in the cells can contribute to or be causal for at least some of these neurodegenerative and systemic diseases (2). However, the direct relationship between the protein deposition and the disease pathology is still controversial. Recent reports suggest that amyloid ␤ (A␤) 2 and other amyloidogenic proteins exert their cellular toxicity as soluble amyloid oligomeric intermediates (amyloid oligomer) but not as insoluble aggregates or fibrils (3-6). These soluble amyloid oligomer proteins generally appear to have ␤-sheet structures, whose formation is correlated with the appearance of a hydrophobic environment (6, 7). Several reports indicate that the soluble amyloid oligomer may be more important in pathogenesis than the insoluble fibrillar amyloid deposits (8 -11). An antibody that specifically recognizes the structure of the amyloid oligomer reacts with oligomers generated from all types of amyloidogenic proteins and peptides, such as A␤-(1-42), ␣-synuclein, polyglutamine, and prions (6). This result implies that the amyloid oligomer has ...

show abstract

“…The production of hB-crystallin and related mammalian proteins such as Hsp27 responds differentially to stress [97 -101, 109, 110], intrinsic agents such as vasopressin [97], and compounds that disassemble microtubules [111]. Induced synthesis of mammalian small heat shock/h-crystallin proteins is elevated by prostaglandins and modulators of arachidonic acid [110,112], and with the exception of hA-crystallin [113], they migrate into nuclei during stress [20,21,114]. Most mammalian small heat shock/h-crystallin proteins exist as oligomers up to 800 kDa in mass and cryoelectron microscopy reveals that human recombinant hBcrystallin multimers are spherical, with diameters of 8 -18 nm [9,72].…”

Section: T H Macraementioning

confidence: 99%

Structure and function of small heat shock/α-crystallin proteins: established concepts and emerging ideas

MacRae¹

2000

CMLS, Cell. Mol. Life Sci.

235

185

View full text Add to dashboard Cite

Small heat shock/alpha-crystallin proteins are defined by conserved sequence of approximately 90 amino acid residues, termed the alpha-crystallin domain, which is bounded by variable amino- and carboxy-terminal extensions. These proteins form oligomers, most of uncertain quaternary structure, and oligomerization is prerequisite to their function as molecular chaperones. Sequence modelling and physical analyses show that the secondary structure of small heat shock/alpha-crystallin proteins is predominately beta-pleated sheet. Crystallography, site-directed spin-labelling and yeast two-hybrid selection demonstrate regions of secondary structure within the alpha-crystallin domain that interact during oligomer assembly, a process also dependent on the amino terminus. Oligomers are dynamic, exhibiting subunit exchange and organizational plasticity, perhaps leading to functional diversity. Exposure of hydrophobic residues by structural modification facilitates chaperoning where denaturing proteins in the molten globule state associate with oligomers. The flexible carboxy-terminal extension contributes to chaperone activity by enhancing the solubility of small heat shock/alpha-crystallin proteins. Site-directed mutagenesis has yielded proteins where the effect of the change on structure and function depends upon the residue modified, the organism under study and the analytical techniques used. Most revealing, substitution of a conserved arginine residue within the alpha-crystallin domain has a major impact on quaternary structure and chaperone action probably through realignment of beta-sheets. These mutations are linked to inherited diseases. Oligomer size is regulated by a stress-responsive cascade including MAPKAP kinase 2/3 and p38. Phosphorylation of small heat shock/alpha-crystallin proteins has important consequences within stressed cells, especially for microfilaments.

show abstract

Enhancement of stress-induced synthesis of hsp27 and αB crystallin by modulators of the arachidonic acid cascade

Cited by 27 publications

References 32 publications

Interaction of intracellular β amyloid peptide with chaperone proteins

Interaction of intracellular β amyloid peptide with chaperone proteins

Interruption of CryAB-Amyloid Oligomer Formation by HSP22

Structure and function of small heat shock/α-crystallin proteins: established concepts and emerging ideas

Contact Info

Product

Resources

About