Departamento de Farmacobiología, Cinvestav-Coapa, Mexico City, Mexico.
Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Cinvestav, Sede Sur, Mexico City, Mexico.
Metab Brain Dis. 2022 Aug;37(6):1863-1874. doi: 10.1007/s11011-022-01033-1. Epub 2022 Jun 27.
Hydrogen sulfide (HS) is a gasotransmitter endogenously synthesized by cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), and 3-mercaptopiruvate sulfurtransferase (3-MST) enzymes. HS exogenous administration prevents the development of hemodynamic impairments after traumatic brain injury (TBI). Since the hypothalamus and the brainstem highly regulate the cardiovascular system, this study aimed to evaluate the effect of NaHS subchronic treatment on the changes of HS-sythesizing enzymes in those brain areas after TBI and in physiological conditions. For that purpose, animals were submitted to a lateral fluid percussion injury, and the changes in CBS, CSE, and 3-MST protein expression were measured by western blot at days 1, 2, 3, 7, and 28 in the vehicle group, and 7 and 28 days after NaHS treatment. After severe TBI induction, we found a decrease in CBS and CSE protein expression in the hypothalamus and brainstem; meanwhile, 3-MST protein expression diminished only in the hypothalamus compared to the Sham group. Remarkably, i.p. daily injections of NaHS, an HS donor, (3.1 mg/kg) during seven days: (1) restored CBS and CSE but no 3-MST protein expression in the hypothalamus at day 28 post-TBI; (2) reestablished only CSE in brainstem 7 and 28 days after TBI; and (3) did not modify HS-sythesizing enzymes protein expression in uninjured animals. Mainly, our results show that the NaHS effect on CBS and CSE protein expression is observed in a time- and tissue-dependent manner with no effect on 3-MST expression, which may suggest a potential role of HS synthesis in hypothalamus and brainstem impairments observed after TBI.
硫化氢 (HS) 是一种内源性气体递质，由胱硫醚-γ-裂解酶 (CSE)、胱硫醚-β-合酶 (CBS) 和 3-巯基丙酮酸硫转移酶 (3-MST) 酶合成。HS 外源性给药可预防创伤性脑损伤 (TBI) 后血流动力学损伤的发展。由于下丘脑和脑干高度调节心血管系统，本研究旨在评估亚慢性 NaHS 处理对 TBI 后和生理条件下这些脑区 HS 合成酶变化的影响。为此，动物接受了侧方液压冲击伤，在载体组中，通过 Western blot 在第 1、2、3、7 和 28 天以及 NaHS 处理后的第 7 和 28 天测量 CBS、CSE 和 3-MST 蛋白表达的变化。在严重 TBI 诱导后，我们发现下丘脑和脑干中 CBS 和 CSE 蛋白表达减少；同时，与 Sham 组相比，3-MST 蛋白表达仅在下丘脑减少。值得注意的是，腹腔内每日注射 HS 供体 NaHS (3.1mg/kg) 7 天：(1) 在 TBI 后第 28 天恢复下丘脑的 CBS 和 CSE，但不恢复 3-MST 蛋白表达；(2) 在 TBI 后 7 和 28 天仅恢复脑干部位的 CSE；(3) 在未受伤的动物中不改变 HS 合成酶蛋白表达。主要的，我们的结果表明，NaHS 对 CBS 和 CSE 蛋白表达的影响是时间和组织依赖性的，对 3-MST 表达没有影响，这可能表明 HS 合成在 TBI 后观察到的下丘脑和脑干损伤中具有潜在作用。
