scholarly journals Proteasome Inhibitors Cause Induction of Heat Shock Proteins and Trehalose, Which Together Confer Thermotolerance inSaccharomyces cerevisiae

1998 ◽  
Vol 18 (1) ◽  
pp. 30-38 ◽  
Author(s):  
Do Hee Lee ◽  
Alfred L. Goldberg
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Proteasome Inhibitor ◽  
Synergistic Effects ◽  
Proteasome Inhibitors ◽  
Reversible Inhibitor ◽  
Unfolded Proteins ◽  
The Common ◽  
Common Signal ◽  
Shock Proteins

ABSTRACT An accumulation in cells of unfolded proteins is believed to be the common signal triggering the induction of heat shock proteins (hsps). Accordingly, in Saccharomyces cerevisiae, inhibition of protein breakdown at 30°C with the proteasome inhibitor MG132 caused a coordinate induction of many heat shock proteins within 1 to 2 h. Concomitantly, MG132, at concentrations that had little or no effect on growth rate, caused a dramatic increase in the cells’ resistance to very high temperature. The magnitude of this effect depended on the extent and duration of the inhibition of proteolysis. A similar induction of hsps and thermotolerance was seen with another proteasome inhibitor, clasto-lactacystin β-lactone, but not with an inhibitor of vacuolar proteases. Surprisingly, when the reversible inhibitor MG132 was removed, thermotolerance decreased rapidly, while synthesis of hsps continued to increase. In addition, exposure to MG132 and 37°C together had synergistic effects in promoting thermotolerance but did not increase hsp expression beyond that seen with either stimulus alone. Although thermotolerance did not correlate with hsp content, another thermoprotectant trehalose accumulated upon exposure of cells to MG132, and the cellular content of this disaccharide, unlike that of hsps, quickly decreased upon removal of MG132. Also, MG132 and 37°C had additive effects in causing trehalose accumulation. Thus, the resistance to heat induced by proteasome inhibitors is not just due to induction of hsps but also requires a short-lived metabolite, probably trehalose, which accumulates when proteolysis is reduced.

Heat shock proteins in proteasome inhibitor related neuropathy

2015 ◽  
Vol 86 ◽  
pp. S27
Author(s):  
Gulce Sari ◽  
Sravani Musuruni ◽  
Grzegorz Wicher ◽  
Jia Mi ◽  
Jonas Bergquist ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Proteasome Inhibitor ◽  
Shock Proteins

Large Potentials of Small Heat Shock Proteins

2011 ◽  
Vol 91 (4) ◽  
pp. 1123-1159 ◽  
Author(s):  
Evgeny V. Mymrikov ◽  
Alim S. Seit-Nebi ◽  
Nikolai B. Gusev
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Muscle Metabolism ◽  
Smooth Muscle Contraction ◽  
Small Heat Shock Proteins ◽  
Unfolded Proteins ◽  
Modern Classification ◽  
Insulin Dependent ◽  
Shock Proteins

Modern classification of the family of human small heat shock proteins (the so-called HSPB) is presented, and the structure and properties of three members of this family are analyzed in detail. Ubiquitously expressed HSPB1 (HSP27) is involved in the control of protein folding and, when mutated, plays a significant role in the development of certain neurodegenerative disorders. HSPB1 directly or indirectly participates in the regulation of apoptosis, protects the cell against oxidative stress, and is involved in the regulation of the cytoskeleton. HSPB6 (HSP20) also possesses chaperone-like activity, is involved in regulation of smooth muscle contraction, has pronounced cardioprotective activity, and seems to participate in insulin-dependent regulation of muscle metabolism. HSPB8 (HSP22) prevents accumulation of aggregated proteins in the cell and participates in the regulation of proteolysis of unfolded proteins. HSPB8 also seems to be directly or indirectly involved in regulation of apoptosis and carcinogenesis, contributes to cardiac cell hypertrophy and survival and, when mutated, might be involved in development of neurodegenerative diseases. All small heat shock proteins play important “housekeeping” roles and regulate many vital processes; therefore, they are considered as attractive therapeutic targets.

scholarly journals Synergistic Effects of Toxic Elements on Heat Shock Proteins

2014 ◽  
Vol 2014 ◽  
pp. 1-17 ◽  
Author(s):  
Khalid Mahmood ◽  
Saima Jadoon ◽  
Qaisar Mahmood ◽  
Muhammad Irshad ◽  
Jamshaid Hussain
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Toxic Elements ◽  
Current Knowledge ◽  
Synergistic Effects ◽  
Expression Patterns ◽  
Expression Levels ◽  
Functional Capabilities ◽  
Shock Proteins ◽  
Diverse Groups

Heat shock proteins show remarkable variations in their expression levels under a variety of toxic conditions. A research span expanded over five decades has revealed their molecular characterization, gene regulation, expression patterns, vast similarity in diverse groups, and broad range of functional capabilities. Their functions include protection and tolerance against cytotoxic conditions through their molecular chaperoning activity, maintaining cytoskeleton stability, and assisting in cell signaling. However, their role as biomarkers for monitoring the environmental risk assessment is controversial due to a number of conflicting, validating, and nonvalidating reports. The current knowledge regarding the interpretation of HSPs expression levels has been discussed in the present review. The candidature of heat shock proteins as biomarkers of toxicity is thus far unreliable due to synergistic effects of toxicants and other environmental factors. The adoption of heat shock proteins as “suit of biomarkers in a set of organisms” requires further investigation.

Heat Shock Proteins and Cytoskeleton Hypothesis in Proteasome Inhibitors-Induced Peripheral Neuropathy

2015 ◽  
Vol 87 ◽  
pp. S68
Author(s):  
Betul Karademir ◽  
Gulce Sari ◽  
Sravani Musuruni ◽  
Grzegorz Wicher ◽  
Tobias Jung ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Proteasome Inhibitors ◽  
Shock Proteins

scholarly journals Corrigendum to “Synergistic Effects of Toxic Elements on Heat Shock Proteins”

2015 ◽  
Vol 2015 ◽  
pp. 1-1 ◽  
Author(s):  
Khalid Mahmood ◽  
Saima Jadoon ◽  
Qaisar Mahmood ◽  
Muhammad Irshad ◽  
Jamshaid Hussain
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Toxic Elements ◽  
Synergistic Effects ◽  
Shock Proteins

Resistance to Bortezomib Develops Slowly in MCL Cells, Extends to the Class of Proteasome Inhibitors, and Is Associated with Decreased Proliferation of the Resistant Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4397-4397 ◽  
Author(s):  
Helena Mora-Jensen ◽  
Edgar G. Rizzatti ◽  
Adrian Wiestner
Keyword(s):  
Cell Cycle ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Protein Expression ◽  
Cell Cycle Control ◽  
Proteasome Inhibitors ◽  
D1 Protein ◽  
Hsp70 Protein ◽  
Cyclin D1 Protein ◽  
Shock Proteins

Abstract Mantle Cell Lymphoma (MCL) is a malignancy of mature B-cells. MCL has a poor prognosis and a limited response to traditional chemotherapy. Bortezomib (BZM), a new powerful inhibitor of the proteasome, can induce responses in up to 50% of relapsed MCL patients, suggesting that in at least half of the patients the lymphoma cells are intrinsically resistant to BZM or rapidly develop resistance during single agent therapy. To investigate possible mechanisms of BZM resistance, we cultured MCL cell lines continuously in sub-lethal concentrations of BZM that were then gradually increased. Resistance was slow to develop taking several months for truly resistant clones to grow out. We generated a bortezomib resistant (BR) clone of HBL-2 with an IC50 of 30nM compared to 5nM in the parental clone and several BR subclones of Jeko-1, the most resistant of which had an IC50 of 200nM compared to 3nM for the parental clone. All BR subclones also showed decreased sensitivity to three other proteasome inhibitors: MG-132, Lactacystin, and NLVS. The increase in IC50 to these drugs was between 3 and 8-fold, consistent with more off-target effects of these drugs compared to BZM. BAY11-7082, an inhibitor of NF-kB signaling, maintained its activity against the resistant cells. Resistance to BZM, once acquired, has remained stable over several months. This is remarkable because the resistant subclones grow significantly slower than the parental lines, even after having been removed from selection for extended periods of time. Consistent with slower cell proliferation, we found reduced Cyclin D1 protein expression in the BZM resistant Jeko clones; however, mRNA levels were comparable to the parental line, indicating that changes in Cyclin D1 protein translation and/or stability may be responsible for the decreased proliferation. BZM resistance has been associated with up-regulation of proteasome components and heat-shock proteins. Indeed, in the resistant HBL-2 subclone we found marked upregulation of two proteasome components (PSMA5 and PSMC1) and of Hsp70 by RT-PCR, but there was only a small change in Hsp70 protein expression. Nevertheless, upregulation of these genes could be part a more global gene expression response as seen with ER-stress and could thus reflect an adaptive change to BZM in the HBL-2 BR subclone. All three Jeko BR clones in contradistinction showed only minor changes in PSMA5, PSMC1 and Hsp70 mRNA expression and surprisingly had markedly reduced Hsp70 protein levels. Thus, in these subclones, BR resistance appears to correlate primarily with changes affecting cell cycle control. We conclude that resistance to BZM may be determined by several mechanisms that affect cell cycle control as well as expression of proteasome components and heat-shock proteins. While the slow development of resistance suggests adaptive changes, its persistence over time is more consistent with mutations or other genomic alterations that are not readily reversible. Ongoing studies aim to more precisely define the basis for BZM resistance in MCL.

Heat shock proteins in willow (Salix viminalis)

1990 ◽  
Vol 80 (2) ◽  
pp. 301-306
Author(s):  
Tiina Vahala ◽  
Tage Eriksson ◽  
Peter Engstrom
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Salix Viminalis ◽  
Shock Proteins
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