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

Stanislav Rodkin; Chizaram Nwosu; Margarita Raevskaya; Maxim Khanukaev; Khava Bekova; Inna Vasilieva; Diana Vishnyak; Anastasia Tolmacheva; Elena Efremova; Mitkhat Gasanov; Anton Tyurin

doi:10.3390/ijms242115708

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

Int J Mol Sci. 2023 Oct 28;24(21):15708. doi: 10.3390/ijms242115708.

Authors

Affiliations

¹ Department of Bioengineering, Faculty of Bioengineering and Veterinary Medicine, Don State Technical University, 344000 Rostov-on-Don, Russia.
² Department of Instrumentation and Biomedical Engineering, Don State Technical University, 344000 Rostov-on-Don, Russia.
³ Department of Nervous Diseases and Neurosurgery, Rostov State Medical University, 344022 Rostov-on-Don, Russia.
⁴ Department of Polyclinic Therapy, N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University, 119435 Moscow, Russia.
⁵ Department of Internal Diseases, Surgut State University, Lenina, 1, Nephrology Department, Surgut District Clinical Hospital, Energetikov, 24/3, 628400 Surgut, Russia.
⁶ Department of Faculty Therapy Named after Professor G.D. Zalessky, Novosibirsk State Medical University, Krasny Prospekt, 52, Department of Medical Rehabilitation, Novosibirsk Regional Clinical Hospital of War Veterans No. 3, Demyan the Poor, 71, 630005 Novosibirsk, Russia.
⁷ Department of Therapy and Occupational Diseases, Ulyanovsk State University, Lev Tolstoy Street 42, 432017 Ulyanovsk, Russia.
⁸ Internal Medicine Department, Institute of Medical Education, The Yaroslav-the-Wise Novgorod State University, Derzhavina St. 6, 173020 Veliky Novgorod, Russia.
⁹ Internal Medicine Department, Bashkir State Medical University, 450008 Ufa, Russia.

Abstract

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 (H₂S) 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, Na₂S) H₂S and a classic inhibitor (aminooxyacetic acid, AOAA) of cystathionine β-synthase (CBS), which is a key enzyme in H₂S synthesis. These studies were carried out on three models of neurotrauma in vertebrates and invertebrates. As a result, it was found that Na₂S 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 Na₂S-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.

Keywords: apoptosis; axotomy; glial cells; hydrogen sulfide; necrosis; neuron; p53; traumatic brain injury.

MeSH terms

Animals
Apoptosis
Axotomy
Brain Injuries, Traumatic*
Cystathionine beta-Synthase / metabolism
Hydrogen Sulfide* / metabolism
Hydrogen Sulfide* / pharmacology
Nerve Tissue* / metabolism
Neuroprotective Agents* / pharmacology
Tumor Suppressor Protein p53 / metabolism

Substances

Hydrogen Sulfide
Tumor Suppressor Protein p53
Neuroprotective Agents
Cystathionine beta-Synthase

Grants and funding

1/CX/CSRD VA/United States