Department of Occupational and Environmental Health, school of public health, Dalian Medical University, Dalian 116044, China.
Department of Environment Hygiene Division, Dalian Center for Disease Control and Prevention, Dalian 116021, China.
Biosci Rep. 2021 Apr 30;41(4). doi: 10.1042/BSR20204264.
Increasing evidence suggests that n-hexane induces nerve injury via neuronal apoptosis induced by its active metabolite 2,5-hexanedione (HD). However, the underlying mechanism remains unknown. Studies have confirmed that pro-nerve growth factor (proNGF), a precursor of mature nerve growth factor (mNGF), might activate apoptotic signaling by binding to p75 neurotrophin receptor (p75NTR) in neurons. Therefore, we studied the mechanism of the proNGF/p75NTR pathway in HD-induced neuronal apoptosis. Sprague-Dawley (SD) rats were injected with 400 mg/kg HD once a day for 5 weeks, and VSC4.1 cells were treated with 10, 20, and 40 mM HD in vitro. Results showed that HD effectively induced neuronal apoptosis. Moreover, it up-regulated proNGF and p75NTR levels, activated c-Jun N-terminal kinase (JNK) and c-Jun, and disrupted the balance between B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax). Our findings revealed that the proNGF/p75NTR signaling pathway was involved in HD-induced neuronal apoptosis; it can serve as a theoretical basis for further exploration of the neurotoxic mechanisms of HD.
越来越多的证据表明，正己烷通过其活性代谢物 2,5-己二酮（HD）诱导神经元凋亡从而引起神经损伤。然而，其潜在的机制仍不清楚。研究已经证实，神经营养因子前体(pro-神经生长因子，proNGF)，一种成熟神经生长因子(mNGF)的前体，可能通过与神经元上的 p75 神经生长因子受体(p75NTR)结合来激活凋亡信号。因此，我们研究了 proNGF/p75NTR 通路在 HD 诱导的神经元凋亡中的作用机制。SD 大鼠每天注射 400mg/kg HD 一次，持续 5 周，体外用 10、20 和 40mM HD 处理 VSC4.1 细胞。结果表明，HD 能有效诱导神经元凋亡。此外，它还上调了 proNGF 和 p75NTR 的水平，激活了 c-Jun N 端激酶（JNK）和 c-Jun，并破坏了 B 细胞淋巴瘤-2（Bcl-2）和 Bcl-2 相关 X 蛋白（Bax）之间的平衡。我们的研究结果表明，proNGF/p75NTR 信号通路参与了 HD 诱导的神经元凋亡，可为进一步探讨 HD 的神经毒性机制提供理论依据。
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