The Role of Hsp70 in Adaptation to Adverse Conditions and Its Possible Medical Application

Abstract

In the present era of global warming and dramatically increased environmental pollution posing a threat to animal life, the understanding and manipulation of organisms' resources of stress tolerance is apparently a question of survival. Heat stress and other forms of stressful factors induce a highly organized response of organisms at the cellular level where heat shock proteins (Hsps) and in particular Hsp70 family of chaperones are among the major players in the protection from the environmental challenge. The present review article summarizes the peculiarities of the Hsp70 family of proteins protective functions being a result of many millions of years of adaptive evolution. It discusses the molecular structure and specific details of hsp70 gene regulation in various organisms, living in diverse climatic zones, with a special emphasis on the protective role of Hsp70 in adverse conditions of the environment. The review discusses the molecular mechanisms underlying Hsp70-specific properties that emerged in the course of adaptation to harsh environmental conditions. This review also includes the data on the anti-inflammatory role of Hsp70 and the involvement of endogenous and recombinant Hsp70 (recHsp70) in proteostatic machinery in various pathologies including neurodegenerative ones such as Alzheimer's and Parkinson's diseases in rodent model organisms and humans in vivo and in vitro. Specifically, the role of Hsp70 as an indicator of disease type and severity and the use of recHsp70 in several pathologies are discussed. The review discusses different roles exhibited by Hsp70 in various diseases including the dual and sometimes antagonistic role of this chaperone in various forms of cancer and viral infection including the SARS-Cov-2 case. Since Hsp70 apparently plays an important role in many diseases and pathologies and has significant therapeutic potential there is a dire need to develop cheap recombinant Hsp70 production and further investigate the interaction of externally supplied and endogenous Hsp70 in chaperonotherapy.

Microplastics dysregulate innate immunity in the SARS-CoV-2 infected lung

“…Hsp70 up-regulation is reported in a range of MP exposure settings including mussels ( 139 ), goldfish ( 140 ) and Daphnia ( 141 ). Hsp70 stress responses are involved in a vast range of pathologies ( 142 ) and play a role in cytoprotection against environmental challenges ( 122 ) including SARS-CoV-2 infection ( 143 ). The top cytokine USR by z score for +MP vs. PBS was IL-1β, a cytokine matured and released via inflammasome activation ( Figure 1 ).…”

Microplastics dysregulate innate immunity in the SARS-CoV-2 infected lung

“…Hsp70 up-regulation is reported in a range of MP exposure settings including mussels (Detree et al, 2018), goldfish (Abarghouei et al, 2021) and Daphnia (Yin et al, 2023b). Hsp70 stress responses are involved in a vast range of pathologies (Nunes et al, 2023) and play a role in inter alia cytoprotection against environmental challenges (Evgen’ev et al, 2023) including SARS-CoV-2 infection (Rébé et al, 2022). The top cytokine USR by z score for +MP vs. PBS was IL-1β, a cytokine matured and released via inflammasome activation (Fig.…”

HSP70 Is a Critical Regulator of HSP90 Inhibitor’s Effectiveness in Preventing HCl-Induced Chronic Lung Injury and Pulmonary Fibrosis

“…HSP70 acts either as an independent chaperone or, together with HSP90, as a co-chaperone [19]. It is associated with various cellular mechanisms with mainly protective functions [20,21]. For example, it blocks the function of protease activator factor 1 (PAF-1), the consequent protein kinase B (AKT) phosphorylation, and the B-cell Lymphoma 2 (Bcl-2) apoptotic pathway [22]; it impedes apoptotic pathways by interfering with caspase-3 and phospholipase A2 activation [23] and plays a critical role in the stress response by modulating the nuclear translocation of heat shock factor-1 (HSF-1).…”