scholarly journals Small Heat Shock Protein 22 Improves Cognition and Learning in the Tauopathic Brain

2022 ◽  
Vol 23 (2) ◽  
pp. 851
Author(s):  
Santiago Rodriguez Ospina ◽  
Danielle Blazier ◽  
Marangelie Criado-Marrero ◽  
Lauren Gould ◽  
Niat Gebru ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Heat Shock ◽  
Transgenic Mice ◽  
Neuronal Loss ◽  
Small Heat Shock Protein ◽  
Functional Benefit ◽  
Canonical Pathways ◽  
Cognition And Learning ◽  
Shock Proteins ◽  
Heat Shock Protein 22

The microtubule-associated protein tau pathologically accumulates and aggregates in Alzheimer’s disease (AD) and other tauopathies, leading to cognitive dysfunction and neuronal loss. Molecular chaperones, like small heat-shock proteins (sHsps), can help deter the accumulation of misfolded proteins, such as tau. Here, we tested the hypothesis that the overexpression of wild-type Hsp22 (wtHsp22) and its phosphomimetic (S24,57D) Hsp22 mutant (mtHsp22) could slow tau accumulation and preserve memory in a murine model of tauopathy, rTg4510. Our results show that Hsp22 protected against deficits in synaptic plasticity and cognition in the tauopathic brain. However, we did not detect a significant change in tau phosphorylation or levels in these mice. This led us to hypothesize that the functional benefit was realized through the restoration of dysfunctional pathways in hippocampi of tau transgenic mice since no significant benefit was measured in non-transgenic mice expressing wtHsp22 or mtHsp22. To identify these pathways, we performed mass spectrometry of tissue lysates from the injection site. Overall, our data reveal that Hsp22 overexpression in neurons promotes synaptic plasticity by regulating canonical pathways and upstream regulators that have been characterized as potential AD markers and synaptogenesis regulators, like EIF4E and NFKBIA.

scholarly journals The Archaeal Small Heat Shock Protein Hsp17.6 Protects Proteins from Oxidative Inactivation

2021 ◽  
Vol 22 (5) ◽  
pp. 2591
Author(s):  
Pengfei Ma ◽  
Jie Li ◽  
Lei Qi ◽  
Xiuzhu Dong
Keyword(s):  
Heat Shock ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Small Heat Shock Protein ◽  
Phase Cell ◽  
Molecular Weights ◽  
Oxidative Inactivation ◽  
Methionine Residues ◽  
Shock Proteins ◽  
And Function

Small heat shock proteins (sHsps) are widely distributed among various types of organisms and function in preventing the irreversible aggregation of thermal denaturing proteins. Here, we report that Hsp17.6 from Methanolobus psychrophilus exhibited protection of proteins from oxidation inactivation. The overexpression of Hsp17.6 in Escherichia coli markedly increased the stationary phase cell density and survivability in HClO and H2O2. Treatments with 0.2 mM HClO or 10 mM H2O2 reduced malate dehydrogenase (MDH) activity to 57% and 77%, whereas the addition of Hsp17.6 recovered the activity to 70–90% and 86–100%, respectively. A similar effect for superoxide dismutase oxidation was determined for Hsp17.6. Non-reducing sodium dodecyl sulfate polyacrylamide gel electrophoresis assays determined that the Hsp17.6 addition decreased H2O2-caused disulfide-linking protein contents and HClO-induced degradation of MDH; meanwhile, Hsp17.6 protein appeared to be oxidized with increased molecular weights. Mass spectrometry identified oxygen atoms introduced into the larger Hsp17.6 molecules, mainly at the aspartate and methionine residues. Substitution of some aspartate residues reduced Hsp17.6 in alleviating H2O2- and HClO-caused MDH inactivation and in enhancing the E. coli survivability in H2O2 and HClO, suggesting that the archaeal Hsp17.6 oxidation protection might depend on an “oxidant sink” effect, i.e., to consume the oxidants in environments via aspartate oxidation

scholarly journals hsp26 of Saccharomyces cerevisiae is related to the superfamily of small heat shock proteins but is without a demonstrable function.

1989 ◽  
Vol 9 (11) ◽  
pp. 5265-5271 ◽  
Author(s):  
R E Susek ◽  
S L Lindquist
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Mutational Analysis ◽  
Small Heat Shock Protein ◽  
Major Effect ◽  
Selfish Dna ◽  
Dna Elements ◽  
Cloned Gene ◽  
Shock Proteins

Analysis of the cloned gene confirms that hsp26 of Saccharomyces cerevisiae is a member of the small heat shock protein superfamily. Previous mutational analysis failed to demonstrate any function for the protein. Further experiments presented here demonstrate that hsp26 has no obvious regulatory role and no major effect on thermotolerance. It is possible that the small heat shock protein genes originated as primitive viral or selfish DNA elements.

scholarly journals The noncanonical small heat shock protein HSP-17 from Caenorhabditis elegans is a selective protein aggregase

2020 ◽  
Vol 295 (10) ◽  
pp. 3064-3079 ◽  
Author(s):  
Manuel Iburg ◽  
Dmytro Puchkov ◽  
Irving U. Rosas-Brugada ◽  
Linda Bergemann ◽  
Ulrike Rieprecht ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Heat Shock ◽  
Small Heat Shock Protein ◽  
Independent Manner ◽  
C Elegans ◽  
Higher Eukaryotes ◽  
Prolonged Heat ◽  
Shock Proteins ◽  
Excretory Organs

Small heat shock proteins (sHsps) are conserved, ubiquitous members of the proteostasis network. Canonically, they act as “holdases” and buffer unfolded or misfolded proteins against aggregation in an ATP-independent manner. Whereas bacteria and yeast each have only two sHsps in their genomes, this number is higher in metazoan genomes, suggesting a spatiotemporal and functional specialization in higher eukaryotes. Here, using recombinantly expressed and purified proteins, static light-scattering analysis, and disaggregation assays, we report that the noncanonical sHsp HSP-17 of Caenorhabditis elegans facilitates aggregation of model substrates, such as malate dehydrogenase (MDH), and inhibits disaggregation of luciferase in vitro. Experiments with fluorescently tagged HSP-17 under the control of its endogenous promoter revealed that HSP-17 is expressed in the digestive and excretory organs, where its overexpression promotes the aggregation of polyQ proteins and of the endogenous kinase KIN-19. Systemic depletion of hsp-17 shortens C. elegans lifespan and severely reduces fecundity and survival upon prolonged heat stress. HSP-17 is an abundant protein exhibiting opposing chaperone activities on different substrates, indicating that it is a selective protein aggregase with physiological roles in development, digestion, and osmoregulation.

scholarly journals Single-molecule fluorescence-based approach reveals novel mechanistic insights into human small heat shock protein chaperone function

2020 ◽  
pp. jbc.RA120.015419
Author(s):  
Caitlin L Johnston ◽  
Nicholas R Marzano ◽  
Bishnu P Paudel ◽  
George Wright ◽  
Justin L.P. Benesch ◽  
...  
Keyword(s):  
Heat Shock ◽  
Single Molecule ◽  
Small Heat Shock Protein ◽  
Vital Role ◽  
Misfolded Proteins ◽  
Single Molecule Fluorescence ◽  
Chaperone Function ◽  
Αb Crystallin ◽  
Client Proteins ◽  
Shock Proteins

Small heat shock proteins (sHsps) are a family of ubiquitous intracellular molecular chaperones that are up-regulated under stress conditions and play a vital role in protein homeostasis (proteostasis). It is commonly accepted that these chaperones work by trapping misfolded proteins to prevent their aggregation; however, fundamental questions regarding the molecular mechanism by which sHsps interact with misfolded proteins remain unanswered. The dynamic and polydisperse nature of sHsp oligomers has made studying them challenging using traditional biochemical approaches. Therefore, we have utilized a single-molecule fluorescence-based approach to observe the chaperone action of human αB-crystallin (αBc, HSPB5). Using this approach we have, for the first time, determined the stoichiometries of complexes formed between αBc and a model client protein, chloride intracellular channel 1 (CLIC1). By examining the dispersity and stoichiometries of these complexes over time, and in response to different concentrations of αBc, we have uncovered unique and important insights into a two-step mechanism by which αBc interacts with misfolded client proteins to prevent their aggregation.

scholarly journals Small heat shock protein of Methanococcus jannaschii, a hyperthermophile

1998 ◽  
Vol 95 (16) ◽  
pp. 9129-9133 ◽  
Author(s):  
Rosalind Kim ◽  
Kyeong Kyu Kim ◽  
Hisao Yokota ◽  
Sung-Hou Kim
Keyword(s):  
Heat Shock ◽  
Citrate Synthase ◽  
Thermal Protection ◽  
Small Heat Shock Protein ◽  
Methanococcus Jannaschii ◽  
Single Chain ◽  
Cell Extracts ◽  
Electron Microscopy Analysis ◽  
Shock Proteins

Small heat shock proteins (sHSPs) belong to a family of 12- to 43-kDa proteins that are ubiquitous and are conserved in amino acid sequence among all organisms. A sHSP homologue of Methanococcus jannaschii, a hyperthermophilic Archaeon, forms a homogeneous multimer comprised of 24 monomers with a molecular mass of 400 kDa in contrast to other sHSPs that show heterogeneous oligomeric complexes. Electron microscopy analysis revealed a spherically shaped oligomeric structure ≈15–20 nm in diameter. The protein confers thermal protection of other proteins in vitro as found in other sHSPs. Escherichia coli cell extracts containing the protein were protected from heat-denatured precipitation when heated up to 100°C, whereas extracts from cells not expressing the protein were heat-sensitive at 60°C. Similar results were obtained when purified sHSP protein was added to an E. coli cell lysate. The protein also prevented the aggregation of two purified proteins: single-chain monellin (SCM) at 80°C and citrate synthase at 40°C.

scholarly journals Small Heat-Shock Proteins Select ΔF508-CFTR for Endoplasmic Reticulum-associated Degradation

2007 ◽  
Vol 18 (3) ◽  
pp. 806-814 ◽  
Author(s):  
Annette Ahner ◽  
Kunio Nakatsukasa ◽  
Hui Zhang ◽  
Raymond A. Frizzell ◽  
Jeffrey L. Brodsky
Keyword(s):  
Endoplasmic Reticulum ◽  
Heat Shock ◽  
Small Heat Shock Protein ◽  
Integral Membrane Protein ◽  
Transmembrane Conductance Regulator ◽  
293 Cells ◽  
Genes Encoding ◽  
Δf508 Cftr ◽  
Shock Proteins ◽  
The Impact

Secreted proteins that fail to achieve their native conformations, such as cystic fibrosis transmembrane conductance regulator (CFTR) and particularly the ΔF508-CFTR variant can be selected for endoplasmic reticulum (ER)-associated degradation (ERAD) by molecular chaperones. Because the message corresponding to HSP26, which encodes a small heat-shock protein (sHsp) in yeast was up-regulated in response to CFTR expression, we examined the impact of sHsps on ERAD. First, we observed that CFTR was completely stabilized in cells lacking two partially redundant sHsps, Hsp26p and Hsp42p. Interestingly, the ERAD of a soluble and a related integral membrane protein were unaffected in yeast deleted for the genes encoding these sHsps, and CFTR polyubiquitination was also unaltered, suggesting that Hsp26p/Hsp42p are not essential for polyubiquitination. Next, we discovered that ΔF508-CFTR degradation was enhanced when a mammalian sHsp, αA-crystallin, was overexpressed in human embryonic kidney 293 cells, but wild-type CFTR biogenesis was unchanged. Because αA-crystallin interacted preferentially with ΔF508-CFTR and because purified αA-crystallin suppressed the aggregation of the first nucleotide-binding domain of CFTR, we suggest that sHsps maintain the solubility of ΔF508-CFTR during the ERAD of this polypeptide.

Regulation of Sam68 activity by small heat shock protein 22

2006 ◽  
Vol 99 (5) ◽  
pp. 1353-1362 ◽  
Author(s):  
Kameswara R. Badri ◽  
Suhasini Modem ◽  
Herve C. Gerard ◽  
Insia Khan ◽  
Mihir Bagchi ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Small Heat Shock Protein ◽  
Heat Shock Protein 22

scholarly journals Buffer’s ionic strength on the chaperone-like activity (CLA) of silkworm small heat shock protein: sHSP19.9 and sHSP20.8

2016 ◽  
Vol 12 (2) ◽  
pp. 241-249
Author(s):  
M Tofazzal Hossain ◽  
Yoichi Aso
Keyword(s):  
Ionic Strength ◽  
Heat Shock ◽  
Small Heat Shock Protein ◽  
High Ionic Strength ◽  
Thermally Induced ◽  
Native Proteins ◽  
Chemically Induced ◽  
Irreversible Aggregation ◽  
Shock Proteins ◽  
Induced Aggregation

Small heat-shock proteins (sHSPs), an abundant and ubiquitous family of molecular chaperones, can effectively prevent irreversible aggregation of non-native proteins by forming soluble complex. The CLA of sHSPs is usually determined by the capacity to suppress thermally or chemically induced protein aggregation. Various factors can effectively influence the CLA, and among them the ionic strength of the preparation and working buffer is an important factor. The study deals with the effect of ionic strength of buffer on the CLA of two silkworm sHSPs: namely sHSP19.9 and sHSP20.8 against the thermally-induced aggregation of BLC, a non-native protein. The study clearly revealed that sHSP19.9 required high ionic strength (more NaCl concentration) in reaction buffer to prevent irreversible aggregation of BLC. On the other hand, such high ionic strength condition is not necessary for sHSP20.8 but it influences the activity in some context.J. Bangladesh Agril. Univ. 12(2): 241-249, December 2014

scholarly journals Small Heat Shock Proteins Produced by Pseudomonas Aeruginosa Clonal Variants Isolated from Diverse Niches

2009 ◽  
Vol 2 ◽  
pp. PRI.S3760 ◽  
Author(s):  
Dinesh Diraviam Sriramulu
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Hypervariable Region ◽  
Small Heat Shock Protein ◽  
Culture Conditions ◽  
Genomic Islands ◽  
Homology Search ◽  
Protein Sequence Analysis ◽  
Standard Culture ◽  
Shock Proteins

Genomic islands interspersed in the chromosome of P. aeruginosa led to inter- and intraclonal diversity. Recently, a particular clone of P. aeruginosa called clone C was isolated from cystic fibrosis (CF) patients, clinical and non-clinical habitats throughout Europe and in Canada. P. aeruginosa clone C strains harbour up to several hundred acquired genes involved in the adaptation of bacteria to diverse niches. Two genes ( hp25 and hp18) from one of the hypervariable regions in the chromosome of clone C strains were highly expressed under standard culture conditions as well as under conditions that mimicked CF sputum environment. Protein sequence analysis revealed that Hp25 and Hp18 belonged to small heat shock protein (sHSP) family. Hp25 protein possessed α-crystallin domain, which is a conserved region among heat shock proteins involved in diverse functions. Sequence homology search revealed that in the Methylobacillus flagellatus genome both genes were situated close to each other and the hp25 gene is found among a few other members of Proteobacteria. Expression of hp25 and hp18 by inter- and intraclonal strains of P. aeruginosa suggested that both genes were present in the stable part of the hypervariable region at the toxR locus and might play a role in their adaptation to diverse niches including the CF lung environment.

Sign in / Sign up

Export Citation Format

Share Document