期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 298, 期 10, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.jbc.2022.102429
关键词
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资金
- National Natural Science Foundation of China [32060212, 81760648]
- Key Project of Yunnan Applied Basic Research ProjectKunming Medical University Union Foundation [202101AY070001006, 2018FE001(-161), 2019FE001, 2019FE001(-020)]
- Yunnan Applied Basic Research Project Foundation [2019FB128]
- Applied Research Foundation of Diagnosis and Treatment Center of Nervous System Diseases of Yunnan Province [ZX2019-03-05]
The study investigated the protective mechanism of the novel antistroke drug OM-LV20 on astrocytes, finding that OM-LV20 may exert protection on astrocytes through the 'PAC1R/JNK/TPH1' axis, highlighting TPH1 as a novel target for antistroke drugs.
Stroke can lead to severe nerve injury and debilitation, resulting in considerable social and economic burdens. Due to the high complexity of post-injury repair mechanisms, drugs approved for use in stroke are extremely scarce, and thus, the discovery of new antistroke drugs and targets is critical. Tryptophan hydroxylase 1 (TPH1) is involved in a variety of mental and neurobehavioral processes, but its effects on stroke have not yet been reported. Here, we used primary astrocyte culture, quantitative real-time PCR, double immunofluores-cence assay, lentiviral infection, cell viability analysis, Western blotting, and other biochemical experiments to explore the protective mechanism of peptide OM-LV20, which previously exhibited neuroprotective effects in rats after ischemic stroke via a mechanism that may involve TPH1. First, we showed that TPH1 was expressed in rat astrocytes. Next, we determined that OM-LV20 impacted expression changes of TPH1 in CTX-TNA2 cells and exhibited a protective effect on the decrease in cell viability and catalase (CAT) levels induced by hydrogen peroxide. Importantly, we also found that TPH1 expression induced by OM-LV20 may be related to the level of change in the pituitary adenylate cyclase-activating peptide type 1 re-ceptor (PAC1R) and to the JNK signaling pathways, thereby exerting a protective effect on astrocytes against oxidative stress. The protective effects of OM-LV20 likely occur via the 'PAC1R/JNK/TPH1' axis, thus highlighting TPH1 as a novel antistroke drug target.
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