The Role of Hydrogen Sulfide in the Localization and Expression of p53 and Cell Death in the Nervous Tissue in Traumatic Brain Injury and Axotomy
2023
Stanislav Rodkin | Chizaram Nwosu | Margarita Raevskaya | Maxim Khanukaev | Khava Bekova | Inna Vasilieva | Diana Vishnyak | Anastasia Tolmacheva | Elena Efremova | Mitkhat Gasanov | Anton Tyurin
Traumatic brain injury (TBI) is one of the leading causes of disability and death worldwide. It is characterized by various molecular–cellular events, with the main ones being apoptosis and damage to axons. To date, there are no clinically effective neuroprotective drugs. In this study, we examined the role of hydrogen sulfide (H<sub>2</sub>S) in the localization and expression of the key pro-apoptotic protein p53, as well as cell death in the nervous tissue in TBI and axotomy. We used a fast donor (sodium sulphide, Na<sub>2</sub>S) H<sub>2</sub>S and a classic inhibitor (aminooxyacetic acid, AOAA) of cystathionine β-synthase (CBS), which is a key enzyme in H<sub>2</sub>S synthesis. These studies were carried out on three models of neurotrauma in vertebrates and invertebrates. As a result, it was found that Na<sub>2</sub>S exhibits a pronounced neuroprotective effect that reduces the number of TUNEL-positive neurons and glial cells in TBI and apoptotic glia in axotomy. This effect could be realized through the Na<sub>2</sub>S-dependent decrease in the level of p53 in the cells of the nervous tissue of vertebrates and invertebrates, which we observed in our study. We also observed the opposite effect when using AOAA, which indicates the important role of CBS in the regulation of p53 expression and death of neurons and glial cells in TBI and axotomy.
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