The Role of p53 Protein in the Realization of the Exogenous Heat Shock Protein 70 Anti-Apoptotic Effect during Axotomy

Abstract

The search for effective neuroprotective agents for the treatment of neurotrauma has always been of great interest to researchers around the world. Extracellular heat shock protein 70 (eHsp70) is considered a promising agent to study, as it has been demonstrated to exert a significant neuroprotective activity against various neurodegenerative diseases. We showed that eHsp70 can penetrate neurons and glial cells when added to the incubation medium, and can accumulate in the nuclei of neurons and satellite glial cells after axotomy. eHsp70 reduces apoptosis and necrosis of the glial cells, but not the neurons. At the same time, co-localization of eHsp70 with p53 protein, one of the key regulators of apoptosis, was noted. eHsp70 reduces the level of the p53 protein apoptosis promoter both in glial cells and in the nuclei and cytoplasm of neurons, which indicates its neuroprotective effect. The ability of eHsp70 to reverse the proapoptotic effect of the p53 activator WR1065 may indicate its ability to regulate p53 activity or its proteosome-dependent degradation.

Prevention by Heat Stimulation of Metabolic Syndrome Progression Based upon the Underlying Molecular Mechanism

“…Demyanenko et al [74] reported that eHSP70 reduces the level of p53 protein and inhibits the pro-apoptotic effect of WR1065 in neurons. This indicates that eHSP70 is involved in regulating p53 activity through the JNK-dependent signaling pathway [74]. The p53 is an important regulator of apoptosis.…”

“…Heat-stimulated HSP70 overexpression is effective in controlling blood sugar levels and suppressing chronic low-grade inflammation in individuals with limited physical activity levels, such as those with severe obesity, muscular dystrophy, people in wheelchairs, and the elderly [62]. Demyanenko et al [74] reported that eHSP70 attenuates apoptosis and necrosis in glial cells, but not in neurons, indicating that eHsp70 also has a neuroprotective effect. Increased eHSP70 expression appears to have little risk of promoting muscle and nerve atrophy [18].…”

Thermal Effect on Heat Shock Protein 70 Family to Prevent Atherosclerotic Cardiovascular Disease

“…[31] Sustained JNK activation promotes apoptosis. [32] eHsp70 reduces apoptosis and necrosis of glial cells, but not neurons.eHsp70 reduces levels of the p53 protein apoptosis promoter (neuroprotective effect). [33] Intranasal injection of recombinant Hsp70 reduced the level of apoptosis in the ischemic penumbra and stimulated axon formation.Exogenous Hsp70 significantly reduced light-induced apoptosis and necrosis of glial cells.…”

“…JNK expression is suppressed as HSP72 expression increases; it has also been shown that JNK inhibits mitochondrial respiration and increases the production of ROS to cause apoptosis [41]. JNK activation is an important step in the cellular response to stress; however, prolonged JNK activation can lead to cell damage and cell death [32]. An increase in HSP72 expression due to thermal stimulation may, in turn, reduce the activity of JNK.…”