Systemic release of heat-shock protein 27 and 70 following severe trauma

Haider, Thomas; Simader, Elisabeth; Gluck, O; Ankersmit, Hendrik Jan; Heinz, Thomas; Hajdu, Stefan; Negrin, Lukas Leopold

doi:10.1038/s41598-019-46034-w

Cited by 16 publications

(14 citation statements)

References 35 publications

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“…HSPs are a family of molecular chaperones maintaining cellular homeostasis [ 84 ]. Extracellular HSPs act as DAMPs and correlate with the severity of several disorders such as sepsis and trauma [ 85 , 86 ]. HSPs can be released passively by necrosis [ 19 , 53 ].…”

Section: Characteristics and Release Mechanisms For Specific Dampsmentioning

confidence: 99%

Release mechanisms of major DAMPs

et al. 2021

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Damage-associated molecular patterns (DAMPs) are endogenous molecules which foment inflammation and are associated with disorders in sepsis and cancer. Thus, therapeutically targeting DAMPs has potential to provide novel and effective treatments. When establishing anti-DAMP strategies, it is important not only to focus on the DAMPs as inflammatory mediators but also to take into account the underlying mechanisms of their release from cells and tissues. DAMPs can be released passively by membrane rupture due to necrosis/necroptosis, although the mechanisms of release appear to differ between the DAMPs. Other types of cell death, such as apoptosis, pyroptosis, ferroptosis and NETosis, can also contribute to DAMP release. In addition, some DAMPs can be exported actively from live cells by exocytosis of secretory lysosomes or exosomes, ectosomes, and activation of cell membrane channel pores. Here we review the shared and DAMP-specific mechanisms reported in the literature for high mobility group box 1, ATP, extracellular cold-inducible RNA-binding protein, histones, heat shock proteins, extracellular RNAs and cell-free DNA.

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Section: Characteristics and Release Mechanisms For Specific Dampsmentioning

confidence: 99%

Release mechanisms of major DAMPs

et al. 2021

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“…Indeed, it has been demonstrated that HSP-70 proteins are released into the blood in severe traumas. Additionally, it was revealed that HSP-70 protein levels were higher in ARDS cases [25]. Therefore, it is possible that the high levels of GRP78 found in the blood of SARS-CoV-2 (+) patients could be derived from the lung tissue.…”

Section: Discussionmentioning

confidence: 99%

Preliminary Virtual Screening Studies to Identify GRP78 Inhibitors Which May Interfere with SARS-CoV-2 Infection

et al. 2020

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SARS-CoV-2 Spike protein was predicted by molecular docking to bind the host cell surface GRP78, which was suggested as a putative good molecular target to inhibit Covid-19. We aimed to confirm that GRP78 gene expression was increased in blood of SARS-CoV-2 (+) versus SARS-CoV-2 (−) pneumonia patients. In addition, we aimed to identify drugs that could be repurposed to inhibit GRP78, thus with potential anti-SARS-CoV-2 activity. Gene expression studies were performed in 10 SARS-CoV-2 (−) and 24 SARS-CoV-2 (+) pneumonia patients. A structure-based virtual screen was performed with 10,761 small molecules retrieved from DrugBank, using the GRP78 nucleotide binding domain and substrate binding domain as molecular targets. Results indicated that GRP78 mRNA levels were approximately four times higher in the blood of SARS-CoV-2 (+) versus SARS-CoV-2 (−) pneumonia patients, further suggesting that GRP78 might be a good molecular target to treat Covid-19. In addition, a total of 409 compounds were identified with potential as GRP78 inhibitors. In conclusion, we found preliminary evidence that further proposes GRP78 as a possible molecular target to treat Covid-19 and that many clinically approved drugs bind GRP78 as an off-target effect. We suggest that further work should be urgently carried out to confirm if GRP78 is indeed a good molecular target and if some of those drugs have potential to be repurposed for SARS-CoV-2 antiviral activity.

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“…HSP27 acts as an intracellular chaperone to maintain normal cell functions, but it is also active extracellularly. HSPs are involved in apoptosis inhibition, cytoprotection, and immunomodulation [ 35 , 36 , 37 , 38 ]. Moreover, HSP27 may play a major role in platelet aggregation by modifying actin polymerization [ 38 , 39 ].…”

Section: Discussionmentioning

confidence: 99%

“…Tian et al [ 39 ] found an association between a high thrombus burden and elevated HSP27 levels in patients with ST elevation myocardial infarctions. In addition, recently, HSP27 was identified as prognostic marker in inflammatory diseases, such as COPD and trauma-related ARDS [ 23 , 24 , 37 , 40 , 41 ]. Therefore, we hypothesized that, in patients with COVID-19, elevated HSP27 might be associated with lung injury.…”

Section: Discussionmentioning

confidence: 99%

Clinical Relevance of Elevated Soluble ST2, HSP27 and 20S Proteasome at Hospital Admission in Patients with COVID-19

Wendt

Lingitz

Laggner

et al. 2021

Biology

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Although, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) represents one of the biggest challenges in the world today, the exact immunopathogenic mechanism that leads to severe or critical Coronavirus Disease 2019 (COVID-19) has remained incompletely understood. Several studies have indicated that high systemic plasma levels of inflammatory cytokines result in the so-called “cytokine storm”, with subsequent development of microthrombosis, disseminated intravascular coagulation, and multiorgan-failure. Therefore, we reasoned those elevated inflammatory molecules might act as prognostic factors. Here, we analyzed 245 serum samples of patients with COVID-19, collected at hospital admission. We assessed the levels of heat shock protein 27 (HSP27), soluble suppressor of tumorigenicity-2 (sST2) and 20S proteasome at hospital admission and explored their associations with overall-, 30-, 60-, 90-day- and in-hospital mortality. Moreover, we investigated their association with the risk of ventilation. We demonstrated that increased serum sST2 was uni- and multivariably associated with all endpoints. Furthermore, we also identified 20S proteasome as independent prognostic factor for in-hospital mortality (sST2, AUC = 0.73; HSP27, AUC = 0.59; 20S proteasome = 0.67). Elevated sST2, HSP27, and 20S proteasome levels at hospital admission were univariably associated with higher risk of invasive ventilation (OR = 1.8; p < 0.001; OR = 1.1; p = 0.04; OR = 1.03, p = 0.03, respectively). These findings could help to identify high-risk patients early in the course of COVID-19.

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Systemic release of heat-shock protein 27 and 70 following severe trauma

Cited by 16 publications

References 35 publications

Release mechanisms of major DAMPs

Release mechanisms of major DAMPs

Preliminary Virtual Screening Studies to Identify GRP78 Inhibitors Which May Interfere with SARS-CoV-2 Infection

Clinical Relevance of Elevated Soluble ST2, HSP27 and 20S Proteasome at Hospital Admission in Patients with COVID-19

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