scholarly journals Neurodegenerative disease-associated protein aggregates are poor inducers of the heat shock response in neuronal-like cells

2020 ◽  
Author(s):  
R. San Gil ◽  
D. Cox ◽  
L. McAlary ◽  
T. Berg ◽  
A. K. Walker ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Neurodegenerative Diseases ◽  
Protein Aggregation ◽  
Neurodegenerative Disease ◽  
Heat Shock Response ◽  
Flow Cytometric Analysis ◽  
Protein Aggregates ◽  
Shock Response ◽  
Shock Proteins

AbstractProtein aggregation that results in the formation of inclusions is strongly correlated with neuronal death and is a pathological hallmark common to many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Huntington’s disease. Cells are thought to dramatically up-regulate the levels of heat shock proteins during periods of cellular stress via induction of the heat shock response (HSR). Heat shock proteins are well-characterised molecular chaperones that interact with aggregation-prone proteins to either stabilise, refold, or traffic protein for degradation. The reason why heat shock proteins are unable to maintain the solubility of particular proteins in neurodegenerative disease is unknown. We sought to determine whether neurodegenerative disease-associated protein aggregates can induce the HSR. Here, we generated a neuroblastoma cell line that expresses a fluorescent reporter under conditions of HSR induction, for example heat shock. Using these cells, we show that the HSR is not induced by exogenous treatment with aggregated forms of Parkinson’s disease-associated α-synuclein or the ALS-associated G93A mutant of superoxide dismutase-1 (SOD1G93A). Furthermore, flow cytometric analysis revealed that intracellular expression of SOD1G93A or a pathogenic form of polyQ-expanded huntingtin (Htt72Q), similarly, results in no or low induction of the HSR. In contrast, expression of a non-pathogenic but aggregation-prone form of firefly luciferase (Fluc) did induce an HSR in a significantly greater proportion of cells. Finally, we show that HSR induction is dependent on the intracellular levels of the aggregation-prone proteins, but the pathogenic proteins (SOD1G93A and Htt72Q) elicit a significantly lower HSR compared to the non-pathogenic proteins (Fluc). These results suggest that pathogenic proteins either evade detection or impair induction of the HSR in neuronal-like cells. Therefore, defective HSR induction may facilitate the initiation of protein aggregation leading to inclusion formation in neurodegenerative diseases.

scholarly journals Characterizing Gene Copy Number of Heat Shock Protein Gene Families in the Emerald Rockcod, Trematomus bernacchii

Genes ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 867
Author(s):  
Anthony D. Tercero ◽  
Sean P. Place
Keyword(s):  
Heat Shock ◽  
Gene Duplication ◽  
Heat Shock Proteins ◽  
Heat Shock Response ◽  
Copy Number ◽  
Gene Families ◽  
Gene Copy ◽  
Shock Response ◽  
Trematomus Bernacchii ◽  
Shock Proteins

The suborder Notothenioidae is comprised of Antarctic fishes, several of which have lost their ability to rapidly upregulate heat shock proteins in response to thermal stress, instead adopting a pattern of expression resembling constitutive genes. Given the cold-denaturing effect that sub-zero waters have on proteins, evolution in the Southern Ocean has likely selected for increased expression of molecular chaperones. These selective pressures may have also enabled retention of gene duplicates, bolstering quantitative output of cytosolic heat shock proteins (HSPs). Given that newly duplicated genes are under more relaxed selection, it is plausible that gene duplication enabled altered regulation of such highly conserved genes. To test for evidence of gene duplication, copy number of various isoforms within major heat shock gene families were characterized via qPCR and compared between the Antarctic notothen, Trematomus bernacchii, which lost the inducible heat shock response, and the non-Antarctic notothen, Notothenia angustata, which maintains an inducible heat shock response. The results indicate duplication of isoforms within the hsp70 and hsp40 super families have occurred in the genome of T. bernacchii. The findings suggest gene duplications may have been critical in maintaining protein folding efficiency in the sub-zero waters and provided an evolutionary mechanism of alternative regulation of these conserved gene families.

Physical Activity, Muscle, and the HSP70 Response

1998 ◽  
Vol 23 (3) ◽  
pp. 245-260 ◽  
Author(s):  
J. Lon Kilgore ◽  
Timothy I. Musch ◽  
Christopher R. Ross
Keyword(s):  
Physical Activity ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Heat Shock Protein ◽  
Heat Shock Response ◽  
Shock Response ◽  
Potential Applications ◽  
Shock Proteins ◽  
External Stimuli ◽  
Exercise And Training

Selye (1936) described how organisms react to various external stimuli (i.e., stressors). These reactions generally follow a programmed series of events and help the organism adapt to the imposed stress. The heat shock response is a common cellular reaction to external stressors, including physical activity. A characteristic set of proteins is synthesised shortly after the organism is exposed to stress. Researchers have not determined how heat shock proteins affect the exercise response. However, their role in adaptation to exercise and training might he inferred, since the synthetic patterns correlate well with the stress adaptation syndrome that Selye described. This review addresses the 70 kilodalton heat shock protein family (HSP70), the most strongly induced heat shock proteins. This paper provides an overview of the general heat shock response and a brief review of literature on HSP70 function, structure, regulation, and potential applications. Potential applications in health, exercise, and medicine are provided. Key words: heat shock, protein, exercise

Heat shock proteins affect RNA processing during the heat shock response of Saccharomyces cerevisiae

1991 ◽  
Vol 11 (2) ◽  
pp. 1062-1068
Author(s):  
H J Yost ◽  
S Lindquist
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Protein Synthesis ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Heat Shock Response ◽  
Rna Splicing ◽  
Yeast Cells ◽  
Yeast Saccharomyces Cerevisiae ◽  
Shock Response ◽  
Shock Proteins

In the yeast Saccharomyces cerevisiae, the splicing of mRNA precursors is disrupted by a severe heat shock. Mild heat treatments prior to severe heat shock protect splicing from disruption, as was previously reported for Drosophila melanogaster. In contrast to D. melanogaster, protein synthesis during the pretreatment is not required to protect splicing in yeast cells. However, protein synthesis is required for the rapid recovery of splicing once it has been disrupted by a sudden severe heat shock. Mutations in two classes of yeast hsp genes affect the pattern of RNA splicing during the heat shock response. First, certain hsp70 mutants, which overproduce other heat shock proteins at normal temperatures, show constitutive protection of splicing at high temperatures and do not require pretreatment. Second, in hsp104 mutants, the recovery of RNA splicing after a severe heat shock is delayed compared with wild-type cells. These results indicate a greater degree of specialization in the protective functions of hsps than has previously been suspected. Some of the proteins (e.g., members of the hsp70 and hsp82 gene families) help to maintain normal cellular processes at higher temperatures. The particular function of hsp104, at least in splicing, is to facilitate recovery of the process once it has been disrupted.

Activation of HSF and selective increase in heat-shock proteins by acute dexamethasone treatment

2000 ◽  
Vol 278 (4) ◽  
pp. H1091-H1097 ◽  
Author(s):  
L. Sun ◽  
J. Chang ◽  
S. R. Kirchhoff ◽  
A. A. Knowlton
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Heat Shock Response ◽  
Cardiac Myocyte ◽  
Adult Rat ◽  
Shock Response ◽  
Cytokine Tumor Necrosis Factor ◽  
Factor Α ◽  
Shock Proteins ◽  
Selective Increase

Heat-shock proteins (HSPs) are an important family of endogenous protective proteins, which increase in response to myocardial ischemia and other stresses. Overexpression of HSP72 is cardioprotective. We were interested in the regulation of heat-shock factor (HSF), the transcription factor for HSP genes. Previously we have observed that the inflammatory cytokine tumor necrosis factor-α increases HSP72 levels and postulated that dexamethasone might effect the heat shock response. In the adult rat cardiac myocyte we found that treatment with either low (10 μM)- or high (100 μM)-dose dexamethasone activated HSF by 2–6 h as determined by gel shift assay without evidence of cytotoxicity. Although HSF activation is a key step in expression of HSP72, this may not result in an increase in HSP72. We found that 10 μM dexamethasone increased HSP72 38%, and 100 μM dexamethasone increased HSP72 62% ( P < 0.05). HSP27 and HSP60 were unchanged. The selective increase in HSP72 was associated with protection of the cardiac myocytes from hypoxia and reoxygenation. We conclude that dexamethasone is a novel inducer of the heat shock response.

Heat-shock response in Legionella pneumophila

1988 ◽  
Vol 34 (10) ◽  
pp. 1148-1153 ◽  
Author(s):  
Michael W. Lema ◽  
Arnold Brown ◽  
Charles A. Butler ◽  
Paul S. Hoffman
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Legionella Pneumophila ◽  
Heat Shock Response ◽  
Temperature Shift ◽  
Bacterial Cells ◽  
Groel Protein ◽  
Shock Response ◽  
Molecular Masses ◽  
Shock Proteins

The heat-shock response of Legionella pneumophila was examined by radiolabelling bacterial cell proteins with [35S]methionine following a temperature shift from 30 to 42 °C. Five heat-shock proteins were identified as having molecular masses of 17, 60, 70, 78, and 85 kilodaltons (kDa). The 85- and 60-kDa proteins were equally distributed between supernatant and pellet fractions following ultracentrifugation at 100 000 × g, the 70- and 78-kDa proteins were found primarily in the supernatant, and the 17-kDa protein was found primarily in the pellet. Synthesis of subsets of the heat-shock proteins could be stimulated by novobiocin, patulin, or puromycin. Ethanol, an effector of the heat-shock response in other microorganisms, had little effect on L. pneumophila, even at the highest concentration tolerated by the bacterial cells (1.9%). Finally, the 60-kDa heat-shock protein of L. pneumophila was immunologically cross-reactive with a polyclonal antibody prepared to the Escherichia coli groEL protein. However, a mouse monoclonal antibody reactive with the 60-kDa protein of all legionellae tested did not cross-react with the E. coli groEL protein, suggesting that the Legionella 60-kDa protein contains common and unique epitopes.

Characterization of the heat-shock response in spinach (Spinacia oleracea L.)

1989 ◽  
Vol 67 (2-3) ◽  
pp. 113-120 ◽  
Author(s):  
Daryl J. Somers ◽  
W. Raymond Cummins ◽  
W. Gary Filion
Keyword(s):  
Protein Synthesis ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Heat Shock Response ◽  
Spinacia Oleracea ◽  
Sodium Dodecyl ◽  
In Vitro Translation ◽  
Spinacia Oleracea L ◽  
Shock Response ◽  
Shock Proteins

Spinach (Spinacia oleracea L. cultivar Longstanding Bloomsdale) grown at 20 °C was subjected to a range of rapid thermal shifts as high as 42 °C. There was a decrease in the level of protein synthesis following heat-shock treatments above 34 °C as indicated by the level of incorporation of L-[35S]methionine. In vivo labelled polypeptides and in vitro translation products of RNA isolated from leaf tissue and analyzed using one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis and fluorography, indicated that the temperature of induction of all 15 heat-shock proteins in the 20 °C grown plants was 36 °C. In addition, heat-shock RNA was coordinately expressed and the translation of heat-shock proteins was noncoordinate with respect to temperature. Treatment with cycloheximide and with chloramphenicol demonstrated that heat-shock protein synthesis in spinach was restricted to cytosolic ribosomes. Synthesis of some low molecular weight heat-shock proteins were insensitive to actinomycin D, suggesting greater stability of these heat-shock RNAs. The heat-shock polypeptide profile of plants grown at 10 °C was similar to that of plants grown at 20 °C, with 14 heat-shock proteins being induced at 36 °C. The growth temperature did not influence the final array of heat-shock proteins synthesized nor alter the temperature of induction of the heat-shock response.Key words: heat-shock response, heat-shock proteins, Spinacia oleracea.

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