Expression, localization and functional divergence of αB-crystallin and heat shock protein 27 in core myopathies and neurogenic atrophy

Fischer, Dirk; Matten, Jens; Reimann, Jens; Bönnemann, Carsten G.; Schröder, Rolf

doi:10.1007/s00401-002-0559-z

Cited by 41 publications

(32 citation statements)

References 16 publications

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“…To examine whether the TNF-␣ -induced malformation of IDs infl uences the position of the ID proteins, we performed similar immunofl uorescent experiments using antibodies against desmoplakin, ␤ -catenin, and connexin 43, which are characteristic proteins of desmosomes, adherent junctions, and gap junctions, plasmic accumulation of small heat shock proteins (HSPs) along with desmin-positive aggregates is an immunohistochemical characteristic of human desminopathies ( Fischer et al, 2002 ), we examined whether desmin colocalizes in these aggregates with the chaperone HSP25. We found that desmin aggregates colocalize with HSP25 ( Fig.…”

Section: Tnf-␣ Overexpression Leads To Progressive Mislocalization Ofmentioning

confidence: 99%

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Desmin mediates TNF-α–induced aggregate formation and intercalated disk reorganization in heart failure

Panagopoulou¹,

Davos

Milner

et al. 2008

The Journal of Cell Biology

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We explored the involvement of the muscle-specific intermediate filament protein desmin in the model of tumor necrosis factor α (TNF-α)–induced cardiomyopathy. We demonstrate that in mice overexpressing TNF-α in the heart (α–myosin heavy chain promoter-driven secretable TNF-α [MHCsTNF]), desmin is modified, loses its intercalated disk (ID) localization, and forms aggregates that colocalize with heat shock protein 25 and ubiquitin. Additionally, other ID proteins such as desmoplakin and β-catenin show similar localization changes in a desmin-dependent fashion. To address underlying mechanisms, we examined whether desmin is a substrate for caspase-6 in vivo as well as the implications of desmin cleavage in MHCsTNF mice. We generated transgenic mice with cardiac-restricted expression of a desmin mutant (D263E) and proved that it is resistant to caspase cleavage in the MHCsTNF myocardium. The aggregates are diminished in these mice, and D263E desmin, desmoplakin, and β-catenin largely retain their proper ID localization. Importantly, D263E desmin expression attenuated cardiomyocyte apoptosis, prevented left ventricular wall thinning, and improved the function of MHCsTNF hearts.

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Section: Tnf-␣ Overexpression Leads To Progressive Mislocalization Ofmentioning

confidence: 99%

“…5 B . Phosphorylation is the major posttranslational modifi cation of HSP25 in response to multiple forms of cellular stress ( Fischer et al, 2002 ). To address whether TNF-␣ induces a posttranslational modifi cation in HSP25, we examined its pattern in 2D gel electrophoresis.…”

Section: Tnf-␣ Overexpression Leads To Progressive Mislocalization Ofmentioning

confidence: 99%

Desmin mediates TNF-α–induced aggregate formation and intercalated disk reorganization in heart failure

Panagopoulou¹,

Davos

Milner

et al. 2008

The Journal of Cell Biology

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“…The DJ1 enables protein refolding and may also be involved in degradation pathways [21]. The HSP-27 has been reported to play a central role in the structural and functional organization of the 3-D intermediate filament and the actin microfilament system [22]. Neufer and Benjamin [23] reported that the pool of immunologically detected HSP-27 was larger in oxidative fibers and increased in response to an increased oxidative metabolism.…”

Section: Oxidative Metabolism-related Proteinsmentioning

confidence: 99%

Differential expression of sarcoplasmic proteins in four heterogeneous ovine skeletal muscles

Hamelin

Sayd

Chambon³

et al. 2007

Proteomics

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Fiber-type distribution is known to vary widely within and between muscles according to differences in muscle functions. 2-DE and MALDI-MS were used to investigate the molecular basis of muscle fiber type-related variability. We compared four lamb skeletal muscles with heterogeneous fiber-type composition that are relatively rich in fast-twitch fiber types, i.e., the semimembranosus, vastus medialis, longissimus dorsi, and tensor fasciae latae (TL). Our results clearly showed that none of the glycolytic metabolism enzymes detected, including TL which was most strongly glycolytic, made intermuscular differentiation possible. Muscle differentiation was based on the differential expression of proteins involved in oxidative metabolism, including not only citric acid cycle enzymes but also other classes of proteins with functions related to oxidative metabolism, oxidative stress, and probably to higher protein turnover. Detected proteins were involved in transport (carbonate dehydratase, myoglobin, fatty acid-binding protein), repair of misfolding damage (heat shock protein (HSP) 60 kDa, HSP-27 kDa, alpha-crystallin beta subunit, DJ1, stress-induced phosphoprotein), detoxification or degradation of impaired proteins (GST-Pi, aldehyde dehydrogenase, peroxiredoxin, ubiquitin), and protein synthesis (tRNA-synthetase). The fractionating method led to the detection of proteins involved in different functions related to oxidative metabolism that have not previously been shown concomitancy.

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“…Accumulation of the small heat shock proteins hsp27 (HspB1) and aB-crystallin along with desmin-positive aggregates is a characteristic, though basically non-specific immuno-histochemical feature in all disease entities listed above as well as in central core disease and neurogenic atrophy [1,3,6,7]. Among a variety of other functions, small heat shock proteins have been postulated to exert an essential role in preventing abnormal protein folding and accumulation [8].…”

Section: Introductionmentioning

confidence: 99%

Hsp27‐2D‐gel electrophoresis is a diagnostic tool to differentiate primary desminopathies from myofibrillar myopathies

et al. 2005

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Small heat shock proteins prevent abnormal protein folding and accumulation. We analyzed the expression of hsp27 and aB-crystallin in skeletal muscle specimens of patients with desminopathies, plectinopathies, myotilinopathy, and other myofibrillar myopathies by means of differential centrifugation, 2D-gel electrophoresis, Western blotting, and mass spectrometry. Hsp27-P82 and -P15 as well as aB-crystallin-P59 and -P45 are the major serine phosphorylation isoforms in normal and diseased human skeletal muscle. 2D-gel-electrophoresis revealed spots of hsp27 in a range of pH 5.3-6.4 in samples of all skeletal muscle specimens, except for the seven desminopathies. They indicated a shift of the main hsp27-spot to alkaline pH degrees, which may help to differentiate primary desminopathies from other myopathies with structural pathology of the desmin cytoskeleton.

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Expression, localization and functional divergence of αB-crystallin and heat shock protein 27 in core myopathies and neurogenic atrophy

Cited by 41 publications

References 16 publications

Desmin mediates TNF-α–induced aggregate formation and intercalated disk reorganization in heart failure

Desmin mediates TNF-α–induced aggregate formation and intercalated disk reorganization in heart failure

Differential expression of sarcoplasmic proteins in four heterogeneous ovine skeletal muscles

Hsp27‐2D‐gel electrophoresis is a diagnostic tool to differentiate primary desminopathies from myofibrillar myopathies

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