Small heat shock proteins and the cytoskeleton: An essential interplay for cell integrity?

Wettstein, Guillaume; Bellaye, Pierre‐Simon; Micheau, Olivier; Bonniaud, P.

doi:10.1016/j.biocel.2012.05.024

Cited by 142 publications

(120 citation statements)

References 78 publications

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“…Most strikingly, highly increased protein levels of HSP27 as well as a tendency for increased αB-crystallin became apparent even during differentiation of plectin-deficient myotubes, indicating that chaperones represented the first line of defense against desmin network aggregation. This is in line with other studies showing that IFs interact with HSPs like HSP70 and HSP90 and especially the small HSPs, HSP27 and αB-crystallin, under conditions of stress (24). Our results demonstrate that, in the case of MFM-mimicking myotubes, protein control mechanisms and chaperone expression are activated but do not secure the cell against protein aggregate formation.…”

Section: Figure 10supporting

confidence: 81%

Chemical chaperone ameliorates pathological protein aggregation in plectin-deficient muscle

Winter¹,

Staszewska²,

Mihailovska³

et al. 2014

J. Clin. Invest.

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The ubiquitously expressed multifunctional cytolinker protein plectin is essential for muscle fiber integrity and myofiber cytoarchitecture. Patients suffering from plectinopathy-associated epidermolysis bullosa simplex with muscular dystrophy (EBS-MD) and mice lacking plectin in skeletal muscle display pathological desmin-positive protein aggregation and misalignment of Z-disks, which are hallmarks of myofibrillar myopathies (MFMs). Here, we developed immortalized murine myoblast cell lines to examine the pathogenesis of plectinopathies at the molecular and single cell level. Plectin-deficient myotubes, derived from myoblasts, were fully functional and mirrored the pathological features of EBS-MD myofibers, including the presence of desmin-positive protein aggregates and a concurrent disarrangement of the myofibrillar apparatus. Using this cell model, we demonstrated that plectin deficiency leads to increased intermediate filament network and sarcomere dynamics, marked upregulation of HSPs, and reduced myotube resilience following mechanical stretch. Currently, no specific therapy or treatment is available to improve plectin-related or other forms of MFMs; therefore, we assessed the therapeutic potential of chemical chaperones to relieve plectinopathies. Treatment with 4-phenylbutyrate resulted in remarkable amelioration of the pathological phenotypes in plectin-deficient myotubes as well as in plectin-deficient mice. Together, these data demonstrate the biological relevance of the MFM cell model and suggest that this model has potential use for the development of therapeutic approaches for EBS-MD.

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Section: Figure 10supporting

confidence: 81%

Chemical chaperone ameliorates pathological protein aggregation in plectin-deficient muscle

Winter¹,

Staszewska²,

Mihailovska³

et al. 2014

J. Clin. Invest.

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“…Small HSP24.1, as described above, increases transiently at 3 h (Fig. 4A), and stabilizes the actin cytoskeleton by regulating actin filament dynamics and preventing aggregation (Dalle-Donne et al, 2001;Wettstein et al, 2012). At 6 h, profilin is increased 2.8-fold (Fig.…”

Section: Structural Responses -Cytoskeleton Extracellular Matrix Andsupporting

confidence: 52%

Rapid proteomic responses to a near-lethal heat stress in the salt marsh musselGeukensia demissa

Fields

Burmester

Cox

et al. 2016

Journal of Experimental Biology

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Acute heat stress perturbs cellular function on a variety of levels, leading to protein dysfunction and aggregation, oxidative stress and loss of metabolic homeostasis. If these challenges are not overcome quickly, the stressed organism can die. To better understand the earliest tissue-level responses to heat stress, we examined the proteomic response of gill from Geukensia demissa, an extremely eurythermal mussel from the temperate intertidal zone of eastern North America. We exposed 15°C-acclimated individuals to an acute near-lethal heat stress (45°C) for 1 h, and collected gill samples from 0 to 24 h of recovery. The changes in protein expression we found reveal a coordinated physiological response to acute heat stress: proteins associated with apoptotic processes were increased in abundance during the stress itself (i.e. at 0 h of recovery), while protein chaperones and foldases increased in abundance soon after (3 h). The greatest number of proteins changed abundance at 6 h; these included oxidative stress proteins and enzymes of energy metabolism. Proteins associated with the cytoskeleton and extracellular matrix also changed in abundance starting at 6 h, providing evidence of cell proliferation, migration and tissue remodeling. By 12 h, the response to acute heat stress was diminishing, with fewer stress and structural proteins changing in abundance. Finally, the proteins with altered abundances identified at 24 h suggest a return to the pre-stress anabolic state.

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“…Heat shock protein β-1 (also known as HSP-27) is a member of small heat shock protein family and is involved in the regulation of apoptosis, protection of cells against oxidative stress and modulation of the cytoskeleton. [43][44] Hence it is plausible that PSP binding modulates the functioning of heat shock protein β-1 leading to induction of apoptosis. In skeletal and cardiac muscle tropomyosin regulates the interaction between actin and myosin, whereas in non-muscle cells it plays a role in regulating the actin cytoskeleton.…”

Section: Identification Of Psp Binding Proteinsmentioning

confidence: 99%

Phenyl Saligenin Phosphate Induced Caspase-3 and c-Jun N-Terminal Kinase Activation in Cardiomyocyte-Like Cells

Felemban

Garner

Smida

et al. 2015

Chem. Res. Toxicol.

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At present, little is known about the effect(s) of organophosphorous compounds (OPs) on cardiomyocytes. In this study we have investigated the effects of phenyl saligenin phosphate (PSP), two organophosphorothioate insecticides (diazinon and chlorpyrifos) and their acutely toxic metabolites (diazoxon and chlorpyrifos oxon) on mitotic and differentiated H9c2 cardiomyoblasts. OP-induced cytotoxicity was assessed by monitoring MTT reduction, LDH release and caspase-3 activity. Cytotoxicity was not observed with diazinon, diazoxon or chlorpyrifos oxon (48 h exposure; 200 µM).Chlorpyrifos-induced cytotoxicity was only evident at concentrations >100 µM. In

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Small heat shock proteins and the cytoskeleton: An essential interplay for cell integrity?

Cited by 142 publications

References 78 publications

Chemical chaperone ameliorates pathological protein aggregation in plectin-deficient muscle

Chemical chaperone ameliorates pathological protein aggregation in plectin-deficient muscle

Rapid proteomic responses to a near-lethal heat stress in the salt marsh musselGeukensia demissa

Phenyl Saligenin Phosphate Induced Caspase-3 and c-Jun N-Terminal Kinase Activation in Cardiomyocyte-Like Cells

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