Department of Neurology, Rui Jin Hospital, Shanghai Jiao Tong University, Shanghai 200025, P.R. China.
Department of Neurology, Xin Hua Hospital, Shanghai Jiao Tong University, Shanghai 200082, P.R. China.
Int J Mol Med. 2018 Jul;42(1):479-488. doi: 10.3892/ijmm.2018.3589. Epub 2018 Mar 27.
Thromboxane A2 receptor (TXA2R) serves a vital role in numerous neurological disorders. Our previous study indicated that SQ29548, an antagonist of TXA2R, attenuated the induced neuron damage in cerebral infarction animals; however, the underlying mechanism remains unknown. Certain studies revealed a new role of TXA2R in the regulation of oxidative stress, which is one of the basic pathological processes in neurological disorders. Thus, the present study attempted to examine whether the inhibition of TXA2R with SQ29548 helped to protect the nerve cells against oxidative stress. SQ29548 was utilized as a TXA2R antagonist, and relevant assays were performed to detect the cell viability, cellular reactive oxygen species (ROS) level, cell apoptosis, expression levels of superoxide dismutase‑2 (SOD2), catalase and caspases, and activation of mitogen‑activated protein kinase (MAPK) pathways. It was observed that hydrogen peroxide (H2O2) dose‑dependently reduced the viability of SH‑SY5Y cells. In addition, H2O2 raised the level of ROS in cells, inhibited the expression levels of SOD2 and catalase, and potentially enhanced cell apoptosis and the expression of caspases via activating the MAPK pathways. Pretreatment with SQ29548 not only rescued the viability of SH‑SY5Y cells, but also ameliorated the intracellular ROS level and the expression levels of SOD2 and catalase. Furthermore, it decreased the cell apoptosis and the expression of caspases, possibly via the inhibition of MAPK pathways. In conclusion, SQ29548, an antagonist of TXA2R, improved the antioxidant capacities of SH‑SY5Y cells and reduced the cell apoptosis through the inhibition of MAPK pathways.
血栓素 A2 受体（TXA2R）在许多神经疾病中起着至关重要的作用。我们之前的研究表明，TXA2R 的拮抗剂 SQ29548 可减轻脑梗死动物中诱导的神经元损伤；然而，其潜在机制尚不清楚。某些研究揭示了 TXA2R 在调节氧化应激中的新作用，氧化应激是神经疾病基本病理过程之一。因此，本研究试图研究用 SQ29548 抑制 TXA2R 是否有助于保护神经细胞免受氧化应激。我们使用 SQ29548 作为 TXA2R 拮抗剂，并进行相关实验来检测细胞活力、细胞活性氧（ROS）水平、细胞凋亡、超氧化物歧化酶 2（SOD2）、过氧化氢酶和半胱天冬酶的表达水平，以及丝裂原激活蛋白激酶（MAPK）通路的激活情况。结果发现，过氧化氢（H2O2）呈剂量依赖性降低 SH-SY5Y 细胞活力。此外，H2O2 增加了细胞内 ROS 水平，抑制了 SOD2 和过氧化氢酶的表达水平，并可能通过激活 MAPK 通路促进细胞凋亡和半胱天冬酶的表达。用 SQ29548 预处理不仅挽救了 SH-SY5Y 细胞的活力，而且改善了细胞内 ROS 水平和 SOD2 和过氧化氢酶的表达水平。此外，它降低了细胞凋亡和半胱天冬酶的表达，可能通过抑制 MAPK 通路。总之，TXA2R 的拮抗剂 SQ29548 通过抑制 MAPK 通路提高了 SH-SY5Y 细胞的抗氧化能力并减少了细胞凋亡。
