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Hydrogen sulfide protects against cell damage through modulation of PI3K/Akt/Nrf2 signaling. 2019

Jiaxin Zhang, and Chaoqun Shi, and Haochen Wang, and Cheng Gao, and Pan Chang, and Xiping Chen, and Haiyan Shan, and Mingyang Zhang, and Luyang Tao
Institute of Forensic Sciences, Soochow University, Suzhou, 215123, China.

Hydrogen sulfide as the third endogenous gaseous mediator had protective effects against traumatic brain injury-induced neuronal damage in mice. However, the exact pathophysiological mechanism underlying traumatic brain injury is complicated and the protective role of H2S is not yet fully known. Therefore, we combined the mechanical injury (scratch) with secondary injury including metabolic impairment (no glucose) together to investigate the underlying cellular mechanism of hydrogen sulfide in vitro models of traumatic brain injury. In the present study, we found that H2S could prevent the scratch-induced decrease in the expression of cystathionine-β-synthetase, a key enzyme involved in the source of hydrogen sulfide, and endogenous hydrogen sulfide generation in PC12 cells. We also found that hydrogen sulfide could prevent scratch-induced cellular injury, alteration of mitochondrial membrane potential, intracellular accumulation of reactive oxygen species and cell death (autophagic cell death and apoptosis) in PC12 cells. It was also found that blocking PI3K/AKT pathway by LY294002, abolished the protection of H2S against scratch-induced cellular reactive oxygen species level and NRF2 accumulation and function in the nucleus. These results suggest that hydrogen sulfide protects against cell damage induced by scratch injury through modulation of the PI3K/Akt/Nrf2 pathway. This study raises the possibility that hydrogen sulfide may have therapeutic efficacy in traumatic brain injury.

UI MeSH Term Description Entries
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006862 Hydrogen Sulfide A flammable, poisonous gas with a characteristic odor of rotten eggs. It is used in the manufacture of chemicals, in metallurgy, and as an analytical reagent. (From Merck Index, 11th ed) Hydrogen Sulfide (H2(Sx)),Hydrogen Sulfide (H2S2),Hydrogen Sulfide (H2S3),Sulfide, Hydrogen
D000070642 Brain Injuries, Traumatic A form of acquired brain injury which occurs when a sudden trauma causes damage to the brain. Trauma, Brain,Traumatic Brain Injury,Encephalopathy, Traumatic,Injury, Brain, Traumatic,TBI (Traumatic Brain Injury),TBIs (Traumatic Brain Injuries),Traumatic Encephalopathy,Brain Injury, Traumatic,Brain Trauma,Brain Traumas,Encephalopathies, Traumatic,TBI (Traumatic Brain Injuries),Traumas, Brain,Traumatic Brain Injuries,Traumatic Encephalopathies
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016923 Cell Death The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. Death, Cell
D051057 Proto-Oncogene Proteins c-akt Protein-serine-threonine kinases that contain PLECKSTRIN HOMOLOGY DOMAINS and are activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. They play a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells. akt Proto-Oncogene Protein,c-akt Protein,AKT1 Protein Kinase,AKT2 Protein Kinase,AKT3 Protein Kinase,Akt-alpha Protein,Akt-beta Protein,Akt-gamma Protein,Protein Kinase B,Protein Kinase B alpha,Protein Kinase B beta,Protein Kinase B gamma,Protein-Serine-Threonine Kinase (Rac),Proto-Oncogene Protein Akt,Proto-Oncogene Protein RAC,Proto-Oncogene Proteins c-akt1,Proto-Oncogene Proteins c-akt2,Proto-Oncogene Proteins c-akt3,RAC-PK Protein,Rac Protein Kinase,Rac-PK alpha Protein,Rac-PK beta Protein,Related to A and C-Protein,c-akt Proto-Oncogene Protein,Akt alpha Protein,Akt beta Protein,Akt gamma Protein,Akt, Proto-Oncogene Protein,Protein, akt Proto-Oncogene,Protein, c-akt Proto-Oncogene,Proteins c-akt1, Proto-Oncogene,Proteins c-akt2, Proto-Oncogene,Proteins c-akt3, Proto-Oncogene,Proto Oncogene Protein Akt,Proto Oncogene Protein RAC,Proto Oncogene Proteins c akt,Proto Oncogene Proteins c akt1,Proto Oncogene Proteins c akt2,Proto Oncogene Proteins c akt3,Proto-Oncogene Protein, akt,Proto-Oncogene Protein, c-akt,RAC PK Protein,RAC, Proto-Oncogene Protein,Rac PK alpha Protein,Rac PK beta Protein,Related to A and C Protein,akt Proto Oncogene Protein,alpha Protein, Rac-PK,c akt Proto Oncogene Protein,c-akt, Proto-Oncogene Proteins,c-akt1, Proto-Oncogene Proteins,c-akt2, Proto-Oncogene Proteins,c-akt3, Proto-Oncogene Proteins
D051267 NF-E2-Related Factor 2 A basic-leucine zipper transcription factor that was originally described as a transcriptional regulator controlling expression of the BETA-GLOBIN gene. It may regulate the expression of a wide variety of genes that play a role in protecting cells from oxidative damage. Nfe2l2 Protein,Nuclear Factor (Erythroid-Derived 2)-Like 2 Protein,Nuclear Factor E2-Related Factor 2,NF E2 Related Factor 2,Nuclear Factor E2 Related Factor 2
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D019869 Phosphatidylinositol 3-Kinases Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell. PI-3 Kinase,Phosphatidylinositol-3-OH Kinase,PtdIns 3-Kinase,PI 3-Kinase,PI-3K,PI3 Kinases,PI3-Kinase,Phosphoinositide 3 Kinases,Phosphoinositide 3-Hydroxykinase,PtdIns 3-Kinases,3-Hydroxykinase, Phosphoinositide,Kinase, PI-3,Kinase, Phosphatidylinositol-3-OH,Kinases, PI3,Kinases, Phosphoinositide 3,PI 3 Kinase,PI3 Kinase,Phosphatidylinositol 3 Kinases,Phosphatidylinositol 3 OH Kinase,Phosphoinositide 3 Hydroxykinase,PtdIns 3 Kinase,PtdIns 3 Kinases

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