Heat Shock Proteins and Diabetes

Zilaee, Marzie; Shirali, Saeed

doi:10.1016/j.jcjd.2016.05.016

Cited by 33 publications

(21 citation statements)

References 92 publications

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“…While the transient activation of Hsf1 and increased expression of Hsps are cytoprotective and protect cells and tissues against myocardial ischemia and injury, hepatotoxicity induced by thioacetamide as well as others (19,39,40), the inhibition of Hsf1 and reduced Hsps mRNAs has been documented in muscle biopsies of patients and animal models with diabetes (41)(42)(43). Indeed, treatment of rodents with Hsp inducers such as bimoclomol or lipoic acid improves insulin sensitivity of type 2 diabetes (44,45).…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Abrogation of heat shock factor 1 (Hsf1) phosphorylation deregulates its activity and lowers activation threshold, leading to obesity in mice

et al. 2017

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Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Abrogation of heat shock factor 1 (Hsf1) phosphorylation deregulates its activity and lowers activation threshold, leading to obesity in mice

et al. 2017

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“…For example, HSP72 has been shown to improve insulin sensitivity and reduce inflammation. It has been observed that in T2D patients, HSP72 expression level was lower than that in their non-diabetic counterparts ( 15 , 18 ). We have studied DNAJB3, another heat shock protein (HSP) that belongs to the HSP40 protein family and observed it to be downregulated in obese individuals and restored following physical exercise ( 14 ).…”

Section: Introductionmentioning

confidence: 98%

Increased Circulation and Adipose Tissue Levels of DNAJC27/RBJ in Obesity and Type 2-Diabetes

et al. 2018

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Heat shock response is an essential cellular stress response. Dysregulation of various heat shock proteins (HSPs), within the heat shock response (HSR) pathway, play a vital role in this host-defense mechanism contributing to obesity-induced insulin resistance and type 2 diabetes (T2D). Previously, we have reported changes in the expression levels of several HSPs such as HSP40, HSP60, HSP70, and HSP90 in obese compared with lean individuals. DNAJC27 is a member of the HSP40 protein family that was previously identified as a body mass index (BMI) associated locus in genome-wide association (GWAS) studies. However, not much is known about the changes in DNAJC27 expression levels in obesity and T2D. In the present study, we aimed at understanding changes in DNAJC27 expression levels in plasma, peripheral blood mononuclear cells (PBMCs) and adipose tissue in association with obesity and T2D. A total of 277 individuals enrolled including 160 non-diabetic (96 non-obese and 64 obese) and 117 T2D (45 non-obese and 72 obese) individuals. Plasma level of DNAJC27 was significantly higher in obese individuals (6.28 ± 0.64 ng/mL) compared with non-obese individuals (4.8 ± 0.45 ng/mL) with P = 0.043. Dividing the population based on diabetes status showed that there was a significant increase in the plasma level of DNAJC27 in obese (6.90 ± 1.3 ng/mL) compared with non-obese individuals (3.81 ± 0.43 ng/mL) (P = 0.033) in the non-diabetic group. Similarly, DNAJC27 expression level was also higher in PBMCs and adipose tissue of obese individuals. DNAJC27 was found to be associated with leptin and resistin, adipokines known to be dysregulated in obesity, that stimulate inflammatory processes leading to metabolic disorders. In conclusion, our data show that DNAJC27 is elevated in obese and T2D individuals and was positively associated with obesity biomarkers such as leptin and resistin suggesting that this protein may play a role in the pathophysiology of these disorders.

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“…Overexpression and or deregulation of heat shock protein (HSP) chaperones have been associated with a number of clinical conditions, including diabetes and cancer 4 . The heat shock protein 90 (HSP90) belongs to a conserved and very ubiquitous group of stress proteins that amounts to ~2% of the total cellular protein content and can be found in all cells in all organisms, from bacteria to humans.…”

mentioning

confidence: 99%

The HSP90 inhibitor Onalespib exerts synergistic anti-cancer effects when combined with radiotherapy: an in vitro and in vivo approach

Spiegelberg

Abramenkovs

Mortensen

et al. 2020

Sci Rep

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Oncogenic client-proteins of the chaperone Heat shock protein 90 (HSP90) insure unlimited tumor growth and are involved in resistance to chemo-and radiotherapy. The HSP90 inhibitor Onalespib initiates the degradation of oncoproteins, and might also act as a radiosensitizer. The aim of this study was therefore to evaluate the efficacy of Onalespib in combination with external beam radiotherapy in an in vitro and in vivo approach. Onalespib downregulated client proteins, lead to increased apoptosis and caused DNA-double-strands. Monotherapy and combination with radiotherapy reduced colony formation, proliferation and migration assessed in radiosensitive HCT116 and radioresistant A431 cells. In vivo, a minimal treatment regimen for 3 consecutive days of Onalespib (3 × 10 mg/kg) doubled survival, whereas Onalespib with radiotherapy (3 × 2 Gy) caused a substantial delay in tumor growth and prolonged the survival by a factor of 3 compared to the HCT116 xenografted control group. Our results demonstrate that Onalespib exerts synergistic anti-cancer effects when combined with radiotherapy, most prominent in the radiosensitive cell models. We speculate that the depletion and downregulation of client proteins involved in signalling, migration and DNA repair mechanisms is the cause. Thus, individually, or in combination with radiotherapy Onalespib inhibits tumor growth and has the potential to improve radiotherapy outcomes, prolonging the overall survival of cancer patients.

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Heat Shock Proteins and Diabetes

Cited by 33 publications

References 92 publications

WITHDRAWN: Abrogation of heat shock factor 1 (Hsf1) phosphorylation deregulates its activity and lowers activation threshold, leading to obesity in mice

WITHDRAWN: Abrogation of heat shock factor 1 (Hsf1) phosphorylation deregulates its activity and lowers activation threshold, leading to obesity in mice

Increased Circulation and Adipose Tissue Levels of DNAJC27/RBJ in Obesity and Type 2-Diabetes

The HSP90 inhibitor Onalespib exerts synergistic anti-cancer effects when combined with radiotherapy: an in vitro and in vivo approach

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