Intracellular and extracellular Hsp70 in cows: Similarities and differences in physiological and pathophysiology conditions
Authors: Petrović Miloš , Đoković Radojica , Kurćubić Vladimir , Bogosavljević-Bošković Snežana , Rakonjac Simeon , Petrović Milun 
Published: June 2024

Heat shock proteins (Hsp), also called chaperones, are proteins that are indispensable for the proper formation of the polypeptide chain; and have a role in its translocation within the cell. Hsp70 in cells helps to re-establish the native conformation of proteins that have denatured under the influence of various stressogens, by preventing their aggregation, which results in protecting the cell from apoptosis and having an anti-inflammatory effect. These proteins are classified on the basis of molecular mass, and the most significant is heat shock protein 70 (Hsp70) with a molecular mass of about 70 kDa, which is designated as "a master player in protein homeostasis". The concentration of Hsp increases significantly when exposed to a stressor originating from the cell itself or from the external environment. Many chaperones are induced under the influence of high ambient temperatures, when the universal heat shock response (HSR) develops, which is why the name heat shock proteins was defined. Intracellular Hsp70 (iHsp70) shows its protective and anti-inflammatory effects. Induced iHsp70 protects the cell from apoptosis by reducing or blocking the activation of caspases, binding to apoptosis-inducing factor (AIF) and inhibiting AIF-induced chromatin condensation or preventing mitochondrial damage and nuclear fragmentation. It blocks cell morphological changes caused by tumor necrosis factor-induced apoptosis, and has been found to aid in cell repair of damage caused by inflammation. The anti-inflammatory effect of iHsp70 is reflected in the fact that it inhibits the response to lipopolysaccharides and blocks the production of inflammatory mediators such as tumor necrosis factor Alpha (TNF-a), and other mechanisms have been described. he expression of the gene for the production of Hsp70 has been well studied in ruminants or their cell cultures exposed to high ambient temperatures, and the multiple increase of iHsp70 in the cells results in a better adaptation to heat stress. The study of eHsp70 has become relevant due to the availability of diagnostic kits for determining its concentration, and the latest results show that it is a very useful predictor of mortality in patients with septic shock. Hsp70 moves to the extracellular space in several ways: after leaving necrotic cells, under the action of various stress factors and inflammation in undamaged cells, it can be produced in the liver as an acute phase protein, and transport by exosomes and direct contact with the lipid membrane of cells have also been described. The pro-inflammatory effect of eHsp70 is realized by inducing immune cells, which further induces the secretion of inflammatory cytokines (TNF-a, IL-1b, IL-6), inducible nitric oxide synthase (iNOS) expression and nuclear translocation of nuclear factor-cB (NF-cB). According to the chaperone balance theory, the higher the value of eHsp70 compared to iHsp70, the more pronounced its proinflammatory effects. This hypothesis was also confirmed in dairy cows in the periparturient period.