The small heat shock protein, HSPB6, in muscle function and disease

Dreiza, Catherine M.; Komalavilas, Padmini; Furnish, Elizabeth J.; Flynn, Charles R.; Sheller, Michael R.; Smoke, Christopher C.; Lopes, Luciana B.; Brophy, Colleen M.

doi:10.1007/s12192-009-0127-8

Cited by 87 publications

(79 citation statements)

References 81 publications

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“…Furthermore, a link between HSP and apoptosis [54], [55] and [56] is ascertained, evidence that endorses the attention on HSP identifications in our time course experiment. HSPB6 has clear roles in smooth and cardiac muscles, while in the skeletal muscle it is less understood [57]. Gusev and colleagues [58] described for HSPB6 a protective role against apoptosis in cardiomyocytes, by means of the inhibition of the activation of procaspase 3 to caspase 3.…”

Section: Omic Clues Towards Apoptosismentioning

confidence: 99%

Apoptosis in muscle-to-meat aging process: The omic witness

Longo

Lana

Bottero

et al. 2015

Journal of Proteomics

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Section: Omic Clues Towards Apoptosismentioning

confidence: 99%

Apoptosis in muscle-to-meat aging process: The omic witness

Longo

Lana

Bottero

et al. 2015

Journal of Proteomics

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“…18,29). P20 peptide decreased F-actin and increased G-actin in intact ASM tissue, and caused disruption of stress fibers in HASM cells, suggesting that the P20 peptide induced relaxation through actin disruption (Figure 2).…”

Section: Discussionmentioning

confidence: 98%

“…P20 peptide has been demonstrated to mimic the biological effect of the entire HSP20 molecule, inducing relaxation in bovine carotid artery (21), porcine coronary artery (26), human saphenous vein (27), human umbilical artery (28), rat aorta (29), bovine ASM (14), and canine ASM (15). In National Institutes of Health 3T3 cells and human ASM (HASM) cells, treatment with the P20 peptide led to depolymerization of actin, resulting in disruption of actin stress fibers (14,15,24).…”

mentioning

confidence: 99%

Heat Shock–Related Protein 20 Peptide Decreases Human Airway Constriction Downstream of β₂-Adrenergic Receptor

Banathy¹,

Cheung‐Flynn²,

Goleniewska³

et al. 2016

Am J Respir Cell Mol Biol

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Severe bronchospasm refractory to b-agonists is a challenging aspect of asthma therapy, and novel therapeutics are needed. b-agonist-induced airway smooth muscle (ASM) relaxation is associated with increases in the phosphorylation of the small heat shock-related protein (HSP) 20. We hypothesized that a transducible phosphopeptide mimetic of HSP20 (P20 peptide) causes relaxation of human ASM (HASM) by interacting with target(s) downstream of the b 2 -adrenergic receptor (b 2 AR) pathway. The effect of the P20 peptide on ASM contractility was determined in human and porcine ASM using a muscle bath. The effect of the P20 peptide on filamentous actin dynamics and migration was examined in intact porcine ASM and cultured primary HASM cells. The efficacy of the P20 peptide in vivo on airway hyperresponsiveness (AHR) was determined in an ovalbumin (OVA) sensitization and challenge murine model of allergic airway inflammation. P20 peptide caused dose-dependent relaxation of carbachol-precontracted ASM and blocked carbachol-induced contraction. The b 2 AR inhibitor, (6)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride (ICI 118,551), abrogated isoproterenol but not P20 peptide-mediated relaxation. The P20 peptide decreased filamentous actin levels in intact ASM, disrupted stress fibers, and inhibited platelet-derived growth factor-induced migration of HASM cells. The P20 peptide treatment reduced methacholine-induced AHR in OVA mice without affecting the inflammatory response. These results suggest that the P20 peptide decreased airway constriction and disrupted stress fibers through regulation of the actin cytoskeleton downstream of b 2 AR. Thus, the P20 peptide may be a potential therapeutic for asthma refractory to b-agonists.Keywords: asthma; airway smooth muscle relaxation; ovalbumin mouse model; peptide therapeutic; filamentous actin Clinical RelevanceInhaled b-agonists are the mainstay of asthma therapy. However, regular use of these drugs has detrimental effects in some patients with asthma, owing to desensitization and/or genetic polymorphism of the b 2 -adrenergic receptor. This article demonstrates that a cell-permeant phosphomimetic peptide of heat shock-related protein 20, P20 peptide, reduced airway hypercontractility by regulating the actin cytoskeleton via mechanism(s) downstream of the adrenergic receptor pathway. Furthermore, inhaled delivery of P20 peptide attenuated methacholine-induced airway hyperresponsiveness in a mouse model of allergic airway inflammation that mimics human asthma. Thus, P20 peptide may be a potential therapeutic for asthma refractory to b-agonists.

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“…Some experimental success has been achieved with simple cell permeant phosphopeptide analogues encompassing the vital PKA consensus site in the N-terminus. Such peptides may confer protection against a variety of diseases including subarachnoid hemorrhage [76], vasospasm of human umbilical artery [77], keloid scarring [78], airway smooth muscle relaxation [77,79] and platelet aggregation [80]. Clearly, all of these peptide agents have therapeutic potential, with one, namely AZX100 [81] having undergone Phase II clinical trials.…”

Section: Disruption Of the Pde4-hsp20 Complexmentioning

confidence: 99%

Targeting Protein–Protein Interactions Within The Cyclic AMP Signaling System As A Therapeutic Strategy for Cardiovascular Disease

2013

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The cAMP signaling system can trigger precise physiological cellular responses that depend on the fidelity of many protein–protein interactions, which act to bring together signaling intermediates at defined locations within cells. In the heart, cAMP participates in the fine control of excitation–contraction coupling, hence, any disregulation of this signaling cascade can lead to cardiac disease. Due to the ubiquitous nature of the cAMP pathway, general inhibitors of cAMP signaling proteins such as PKA, EPAC and PDEs would act non-specifically and universally, increasing the likelihood of serious ‘off target’ effects. Recent advances in the discovery of peptides and small molecules that disrupt the protein–protein interactions that underpin cellular targeting of cAMP signaling proteins are described and discussed.

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The small heat shock protein, HSPB6, in muscle function and disease

Cited by 87 publications

References 81 publications

Apoptosis in muscle-to-meat aging process: The omic witness

Apoptosis in muscle-to-meat aging process: The omic witness

Heat Shock–Related Protein 20 Peptide Decreases Human Airway Constriction Downstream of β₂-Adrenergic Receptor

Targeting Protein–Protein Interactions Within The Cyclic AMP Signaling System As A Therapeutic Strategy for Cardiovascular Disease

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The small heat shock protein, HSPB6, in muscle function and disease

Cited by 87 publications

References 81 publications

Apoptosis in muscle-to-meat aging process: The omic witness

Apoptosis in muscle-to-meat aging process: The omic witness

Heat Shock–Related Protein 20 Peptide Decreases Human Airway Constriction Downstream of β2-Adrenergic Receptor

Targeting Protein–Protein Interactions Within The Cyclic AMP Signaling System As A Therapeutic Strategy for Cardiovascular Disease

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Heat Shock–Related Protein 20 Peptide Decreases Human Airway Constriction Downstream of β₂-Adrenergic Receptor