Open AccessNeuroprotective effect of hydrogen sulfide against glutamate-induced oxidative stress is mediated via the p53/glutaminase 2 pathway after traumatic brain injury
Author(s) -
Jianping Sun,
Xiaoyü Li,
Xiaolei Gu,
Hongwei Du,
Gengshen Zhang,
Jing Wu,
Feng Wang
Publication year - 2021
Publication title -
aging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 90
ISSN - 1945-4589
DOI - 10.18632/aging.202575
Subject(s) - neuroprotection , glutamate receptor , oxidative stress , glutaminase , traumatic brain injury , hydrogen sulfide , chemistry , neuroscience , pharmacology , biochemistry , medicine , biology , psychiatry , receptor , sulfur , organic chemistry
Several reports suggest that hydrogen sulfide (H 2 S) exerts multiple biological and physiological effects on the pathogenesis of traumatic brain injury (TBI). However, the exact molecular mechanism involved in this effect is not yet fully known. In this study, we found that H 2 S alleviated TBI-induced motor and spatial memory deficits, brain pathology, and brain edema. Moreover, sodium hydrosulfide (NaHS), an H 2 S donor, treatment markedly increased the expression of Bcl-2, while inhibited the expression of Bax and Cleaved caspase-3 in TBI-challenged rats. Tunnel staining also demonstrated these results. Treatment with NaHS significantly reduced the glutamate and glutaminase 2 (GLS-2) protein levels, and glutamate-mediated oxidative stress in TBI-challenged rats. Furthermore, we demonstrated that H 2 S treatment inhibited glutamate-mediated oxidative stress through the p53/GLS-2 pathway. Therefore, our results suggested that H 2 S protects brain injury induced by TBI through modulation of the glutamate-mediated oxidative stress in the p53/GLS-2 pathway-dependent manner.