Small Heat Shock Proteins and Protection Against Ischemic Injury in Cardiac Myocytes

Martin, J.L.; Mestril, Ruben; Hilal-Dandan, Randa; Brunton, Laurence L.; Dillmann, Wolfgang H.

doi:10.1161/01.cir.96.12.4343

Cited by 320 publications

(229 citation statements)

References 32 publications

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“…68 When a cell is subjected to stress, alphaB-crystallin protects muscle fibers from the effects of ischemia. 69 AlphaBcrystallin participates in a number of other cellular processes, helping to modulate correct protein-folding, compartment-targeting, degradation and signaling.…”

Section: Cryab and Alphab-crystallinmentioning

confidence: 99%

Intermediate Filament Diseases: Desminopathy

Goldfarb

Olivé

Vicart³

et al. 2008

Advances in Experimental Medicine and Biology

107

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Desminopathy is one of the most common intermediate filament human disorders associated with mutations in closely interacting proteins, desmin and alphaB-crystallin. The inheritance pattern in familial desminopathy is characterized as autosomal dominant or autosomal recessive, but many cases have no family history. At least some and likely most sporadic desminopathy cases are associated with de novo DES mutations. The age of disease onset and rate of progression may vary depending on the type of inheritance and location of the causative mutation. Typically, the illness presents with lower and later upper limb muscle weakness slowly spreading to involve truncal, neckflexor, facial and bulbar muscles. Skeletal myopathy is often combined with cardiomyopathy manifested by conduction blocks, arrhythmias and chronic heart failure resulting in premature sudden death. Respiratory muscle weakness is a major complication in some patients. Sections of the affected skeletal and cardiac muscles show abnormal fibre areas containing chimeric aggregates consisting of desmin and other cytoskeletal proteins. Various DES gene mutations: point mutations, an insertion, small in-frame deletions and a larger exon-skipping deletion, have been identified in desminopathy patients. The majority of these mutations are located in conserved alpha-helical segments, but additional mutations have recently been identified in the tail domain. Filament and network assembly studies indicate that most but not all disease-causing mutations make desmin assembly-incompetent and able to disrupt a pre-existing filamentous network in dominant-negative fashion. AlphaBcrystallin serves as a chaperone for desmin preventing its aggregation under various forms of stress; mutant CRYAB causes cardiac and skeletal myopathies identical to those resulting from DES mutations.

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Section: Cryab and Alphab-crystallinmentioning

confidence: 99%

Intermediate Filament Diseases: Desminopathy

Goldfarb

Olivé

Vicart³

et al. 2008

Advances in Experimental Medicine and Biology

107

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“…Actin, in particular, has been found to be protected by the small HSPs [Snoeckx et al, 2001], which is important not only for the cytoskeleton of all cells, but also for the sarcomeres in cardiac tissue. In addition to preconditioning studies, which tend to induce a variety of protective stress proteins, transgenic studies in vitro [Martin et al, 1997;Brar et al, 1999;Vander Heide, 2001] have demonstrated that increasing levels of Hsp25/27 prior to simulated ischemia-reperfusion injuries can have a protective effect. Miyakawa et al [2001] found that the temperature required for a given expression of a reporter gene (lacZ) under HSP16 promoter control in transgenic nematode worms was reduced after exposure to a 60 Hz magnetic field at up to 0.5 T. Leszczynski et al [2002] saw an increase in protein phosphorylation and Hsp27 expression after exposure to a 900 MHz GSM signal.…”

Section: Mechanisms: Heat Shock Proteinsmentioning

confidence: 99%

The influence of extremely low frequency magnetic fields on cytoprotection and repair

Robertson

Thomas

Bureau

et al. 2006

Bioelectromagnetics

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Ischemia-reperfusion injuries, such as those suffered from various types of cardiovascular disease, are major causes of death and disability. For relatively short periods of ischemia, much of the damage is potentially reversible and in fact, does not occur until the influx of oxygen during the reperfusion stage. Because of this, there is a window of opportunity to protect the ischemic tissue. Here, we review several mechanisms of protection, such as heat shock proteins, opioids, collateral blood flow, and nitric oxide induction, and the evidence indicating that magnetic fields may be used as a means of providing protection via each of these mechanisms. While there are few studies demonstrating direct protection with magnetic field therapies, there are a number of published reports indicating that electromagnetic fields may be able to influence some of the biochemical systems with protective applications.

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“…Concerning the role of phosphorylation on HSP function other studies have shown that HSP27 oligomerization and chaperone function are down regulated by phosphorylation [28] and HSP70 phosphorylation is significantly reduced by heat stress [29]. HSP90 phosphorylation plays an important role on the stimulation of eIF-2a kinase activity [15] and on the regulation of the interaction with pp60v-src [16].…”

Section: Polyacrylamide Gel Electrophoresismentioning

confidence: 99%

Phosphorylation and oligomerization states of native pig brain HSP90 studied by mass spectrometry

Garnier

Lafitte

Jørgensen

et al. 2001

European Journal of Biochemistry

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HSP90 is one of the most abundant proteins in the cytosol of eukaryotic cells. HSP90 forms transient or stable complexes with several key proteins involved in signal transduction including protooncogenic protein kinases and nuclear receptors, it interacts with cellular structural elements such as actin-microfilament, tubulin-microtubule and intermediate filaments, and also exhibits conventional chaperone functions. This protein exists in two isoforms a-HSP90 and b-HSP90, and it forms dimers which are crucial species for its biological activity. PAGE, ESI-MS and MALDI-MS were used to study HSP90 purified from pig brain. The two protein isoforms were clearly distinguished by ESI-MS, the a isoform being < six times more abundant than the b isoform. ESI-MS in combination with l phosphatase treatment provided direct evidence of the existence of four phosphorylated forms of native pig brain a-HSP90, with the diphosphorylated form being the most abundant. For the b isoform, the di-phosphorylated was also the most abundant. MALDI mass spectra of HSP90 samples after chemical cross-linking showed a high percentage of a±a homodimers. In addition, evidence for the existence of higher HSP90 oligomers was obtained.Keywords: HSP90; mass spectrometry; phosphorylation; cross-linking.Heat shock proteins (HSP) are abundant eukaryotic proteins constituting < 1 or 2% of the cellular proteins under physiological conditions, with an increased expression in response to stress [1]. These ubiquitous proteins, classified according to their apparent molecular mass, i.e. HSP27, 60, 70 or 90, work in close association with cytosolic cofactors to help the correct folding of several cytosolic proteins (reviewed in [2]).The target of this study is HSP90, a dimeric phosphoprotein involved in many cell processes such as cell cycle control, transcriptional regulation or signal transduction (reviewed in [3]). Mammalian HSP90 exists in two isoforms a-and b-HSP90 [4], differing in mass by < 2 kDa. Although dimers appear to be the functional form of HSP90, oligomeric forms exist in solution under physiological conditions [5] and their amount tends to increase under hyperthermal exposure [6±9]. HSP90 possesses an ATP binding site [10,11] and undergoes conformational changes in presence of ATP [12,13]. This protein also possesses ATPase activity [14]. The functions of HSP90 are in part regulated by phosphorylation, e.g. phosphorylated HSP90 stimulates eIF-2a kinase activity [15] and phosphorylation regulates the interaction between HSP90 and pp60v-src [16]. HSP phosphorylation may be mediated by various kinases [17,18] but this protein can also autophosphorylate and act as a kinase for other protein substrates [19].ESI-MS and MALDI-MS are the most suitable mass spectrometric techniques for the analysis of macromolecules [20,21]. The increase in resolution achieved by the latest generation of mass spectrometers allows a detailed investigation of post-translational modifications of large proteins and protein complexes [22]. This is particularly important ...

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Small Heat Shock Proteins and Protection Against Ischemic Injury in Cardiac Myocytes

Cited by 320 publications

References 32 publications

Intermediate Filament Diseases: Desminopathy

Intermediate Filament Diseases: Desminopathy

The influence of extremely low frequency magnetic fields on cytoprotection and repair

Phosphorylation and oligomerization states of native pig brain HSP90 studied by mass spectrometry

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