The Invalidation of HspB1 Gene in Mouse Alters the Ultrastructural Phenotype of Muscles

Kammoun, Malek; Picard, Brigitte; Astruc, Thierry; Gagaoua, Mohammed; Aubert, Denise; Bonnet, Muriel; Blanquet, Véronique; Cassar-Malek, Isabelle

doi:10.1371/journal.pone.0158644

Cited by 20 publications

(16 citation statements)

References 54 publications

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“…However, in skeletal muscle, HSPB1 loss decreases resistance to repetitive muscle fatigue and HSPB1 −/− mice display decreased voluntary running 10 . Notably, macroscopic examination of soleus muscle tissue from HSPB1 −/− mice failed to reveal any structural alterations and only electron microscopy was able to detect minor myofibril changes 39 . Since in situ hybridization studies on HSPB1 expression in mouse tissues identified elevated mRNA levels in the arterial system 6 and a preliminary microarray experiment from MEFs lacking HSPB1 demonstrated altered elastin levels (data not shown), we examined whether loss of HSPB1 adversely affected arterial structure and function in septic mice.…”

Section: Discussionmentioning

confidence: 98%

The small heat shock protein HSPB1 protects mice from sepsis

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Hilliard

Yoseph

et al. 2018

Sci Rep

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In vitro studies have implicated the small heat shock protein HSPB1 in a range of physiological functions. However, its in vivo relevance is unclear as the phenotype of unstressed HSPB1−/− mice is unremarkable. To determine the impact of HSPB1 in injury, HSPB1−/− and wild type (WT) mice were subjected to cecal ligation and puncture, a model of polymicrobial sepsis. Ten-day mortality was significantly higher in HSPB1−/− mice following the onset of sepsis (65% vs. 35%). Ex vivo mechanical testing revealed that common carotid arteries from HSPB1−/− mice were more compliant than those in WT mice over pressures of 50–120 mm Hg. Septic HSPB1−/− mice also had increased peritoneal levels of IFN-γ and decreased systemic levels of IL-6 and KC. There were no differences in frequency of either splenic CD4+ or CD8+ T cells, nor were there differences in apoptosis in either cell type. However, splenic CD4+ T cells and CD8+ T cells from HSPB1−/− mice produced significantly less TNF and IL-2 following ex vivo stimulation. Systemic and local bacterial burden was similar in HSPB1−/− and WT mice. Thus while HSPB1−/− mice are uncompromised under basal conditions, HSPB1 has a critical function in vivo in sepsis, potentially mediated through alterations in arterial compliance and the immune response.

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Section: Discussionmentioning

confidence: 98%

The small heat shock protein HSPB1 protects mice from sepsis

Breed

Hilliard

Yoseph

et al. 2018

Sci Rep

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“…HSP27-encoded by HspB1 is constitutively present in a wide variety of tissues and in many cell lines. The abundance of HSP27 is greater in skeletal muscle, indicating an important role for muscle physiology ( Kammoun et al, 2016 ) and thus for muscle to meat conversion ( Picard & Gagaoua, 2017 ; Picard, Gagaoua & Hollung, 2017b ). An earlier study by our group showed that it is at a crucial hub in a functional network involved in beef tenderness ( Guillemin et al, 2011a ).…”

Section: Discussionmentioning

confidence: 99%

Beef tenderness and intramuscular fat proteomic biomarkers: muscle type effect

Picard

Gagaoua

Al-Jammas

et al. 2018

PeerJ

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Tenderness and intramuscular fat content are key attributes for beef sensory qualities. Recently some proteomic analysis revealed several proteins which are considered as good biomarkers of these quality traits. This study focuses on the analysis of 20 of these proteins representative of several biological functions: muscle structure and ultrastructure, muscle energetic metabolism, cellular stress and apoptosis. The relative abundance of the proteins was measured by Reverse Phase Protein Array (RPPA) in five muscles known to have different tenderness and intramuscular lipid contents: Longissimus thoracis (LT), Semimembranosus (SM), Rectus abdominis (RA), Triceps brachii (TB) and Semitendinosus (ST). The main results showed a muscle type effect on 16 among the 20 analyzed proteins. They revealed differences in protein abundance depending on the contractile and metabolic properties of the muscles. The RA muscle was the most different by 11 proteins differentially abundant comparatively to the four other muscles. Among these 11 proteins, six were less abundant namely enolase 3 (ENO3), phosphoglucomutase 1 (PGK1), aldolase (ALDOA), myosin heavy chain IIX (MyHC-IIX), fast myosin light chain 1 (MLC1F), triosephosphate isomerase 1 (TPI1) and five more abundant: Heat shock protein (HSP27, HSP70-1A1, αB-crystallin (CRYAB), troponin T slow (TNNT1), and aldolase dehydrogenase 1 (ALDH1A1). Four proteins: HSP40, four and a half LIM domains protein 1 (FHL1), glycogen phosphorylase B (PYGB) and malate dehydrogenase (MDH1) showed the same abundance whatever the muscle. The correlations observed between the 20 proteins in all the five muscles were used to construct a correlation network. The proteins the most connected with the others were in the following order MyHC-IIX, CRYAB, TPI1, PGK1, ALDH1A1, HSP27 and TNNT1. This knowledge is important for understanding the biological functions related to beef tenderness and intramuscular fat content.

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“…The absence of myofiber defect was unexpected, since HSPB8 participates in myofibril stabilisation through the CASA complex [ 38 , 79 , 80 ]. Furthermore, depletion of Hspb1, another member of the sHSP family whose mutant form has also been associated with myopathy, leads to myofiber ultrastructural defects [ 46 ]. Although the Hspb8 −/− myofibers did not undergo atrophy and degeneration, they presented an accumulation of abnormally patterned mitochondria.…”

Section: Discussionmentioning

confidence: 99%

A knock-in/knock-out mouse model of HSPB8-associated distal hereditary motor neuropathy and myopathy reveals toxic gain-of-function of mutant Hspb8

et al. 2017

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Mutations in the small heat shock protein B8 gene (HSPB8/HSP22) have been associated with distal hereditary motor neuropathy, Charcot–Marie–Tooth disease, and recently distal myopathy. It is so far not clear how mutant HSPB8 induces the neuronal and muscular phenotypes and if a common pathogenesis lies behind these diseases. Growing evidence points towards a role of HSPB8 in chaperone-associated autophagy, which has been shown to be a determinant for the clearance of poly-glutamine aggregates in neurodegenerative diseases but also for the maintenance of skeletal muscle myofibrils. To test this hypothesis and better dissect the pathomechanism of mutant HSPB8, we generated a new transgenic mouse model leading to the expression of the mutant protein (knock-in lines) or the loss-of-function (functional knock-out lines) of the endogenous protein Hspb8. While the homozygous knock-in mice developed motor deficits associated with degeneration of peripheral nerves and severe muscle atrophy corroborating patient data, homozygous knock-out mice had locomotor performances equivalent to those of wild-type animals. The distal skeletal muscles of the post-symptomatic homozygous knock-in displayed Z-disk disorganisation, granulofilamentous material accumulation along with Hspb8, αB-crystallin (HSPB5/CRYAB), and desmin aggregates. The presence of the aggregates correlated with reduced markers of effective autophagy. The sciatic nerve of the homozygous knock-in mice was characterized by low autophagy potential in pre-symptomatic and Hspb8 aggregates in post-symptomatic animals. On the other hand, the sciatic nerve of the homozygous knock-out mice presented a normal morphology and their distal muscle displayed accumulation of abnormal mitochondria but intact myofiber and Z-line organisation. Our data, therefore, suggest that toxic gain-of-function of mutant Hspb8 aggregates is a major contributor to the peripheral neuropathy and the myopathy. In addition, mutant Hspb8 induces impairments in autophagy that may aggravate the phenotype.Electronic supplementary materialThe online version of this article (doi:10.1007/s00401-017-1756-0) contains supplementary material, which is available to authorized users.

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The Invalidation of HspB1 Gene in Mouse Alters the Ultrastructural Phenotype of Muscles

Cited by 20 publications

References 54 publications

The small heat shock protein HSPB1 protects mice from sepsis

The small heat shock protein HSPB1 protects mice from sepsis

Beef tenderness and intramuscular fat proteomic biomarkers: muscle type effect

A knock-in/knock-out mouse model of HSPB8-associated distal hereditary motor neuropathy and myopathy reveals toxic gain-of-function of mutant Hspb8

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