Extracellular Signal-Regulated Kinase 1/2 Pathway Is Insufficiently Involved in the Neuroprotective Effect by Hydrogen Sulfide Supplement in Experimental Glaucoma
Extracellular Signal-Regulated Kinase 1/2 Pathway Is Insufficiently Involved in the Neuroprotective Effect by Hydrogen Sulfide Supplement in Experimental Glaucoma
复制标题
细胞外信号调节激酶 1/2 通路未充分参与硫化氢补充剂对实验性青光眼的神经保护作用
DOI：
10.1167/iovs.19-27507
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发表时间：
2019-10-01
影响因子：
4.4
通讯作者：
Zhong, Yisheng
中科院分区：
文献类型：
--
作者：
Huang, Shouyue;Huang, Ping;Zhong, Yisheng
目的。青光眼是一种神经退行性眼病，其特征是由于视网膜神经节细胞（RGC）损失导致视野逐渐受损和不可逆性失明。我们之前的研究已证实硫化氢（H2S）参与青光眼过程并有助于保护RGC。本研究旨在进一步探讨细胞外信号调节激酶1/2（ERK 1/2）通路在H2S影响中的作用，以更好地了解H2S对青光眼发挥神经保护作用的机制。采用已建立的大鼠青光眼模型，168只大鼠符合条件接受硫氢化钠（NaHS，H2S供体）/PD98059（ERK抑制剂）治疗。然后通过逆行标记和TUNEL染色评估RGC的存活和凋亡，并通过ERK 1/2途径、内在凋亡途径、胶质细胞活化、核因子κB（NF-κB）途径、烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶、自噬和TNF-α产生的活性评估 免疫组织化学、Western blotting 和 ELISA。结果。研究表明，在实验性青光眼大鼠的视网膜中，NaHS 与 PD98059 类似地抑制 ERK 1/2 通路活性，而 PD98059 也类似地抑制神经胶质活化、NF-kappa B 通路、NADPH 氧化酶和 TNF-α 产生。然而，PD98059 并不像 NaHS 那样影响 RGC 存活、细胞凋亡调节或自噬。结论。我们的研究表明，抑制 ERK 1/2 通路可能部分有助于 H2S 对实验性青光眼的神经保护作用。然而，其本身不足以引发治疗效果。
PURPOSE. Glaucoma is a neurodegenerative eye disease characterized by gradually impaired visual field and irreversible blindness due to retinal ganglion cell (RGC) loss. Our previous studies have confirmed that hydrogen sulfide (H2S) takes part in the glaucomatous process and contributes to RGC protection. The present study aimed to further investigate the role of extracellular signal-regulated kinase 1/2 (ERK 1/2) pathway underlying the impact of H2S, to better understand the mechanism through which H2S exerts neuroprotection in glaucoma.METHODS. An established rat glaucoma model was used and 168 rats were qualified to undergo sodium hydrosulfide (NaHS, a H2S donor)/PD98059 (an ERK inhibitor) treatment. Then the survival and apoptosis of RGC were evaluated through retrograde labeling and TUNEL staining, along with activity evaluations of ERK 1/2 pathway, intrinsic apoptotic pathway, glial activation, nuclear factor kappa B (NF-kappa B) pathway, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, autophagy, and TNF-alpha production through immunohistochemistry, Western blotting, and ELISA.RESULTS. The study demonstrated that NaHS suppressed ERK 1/2 pathway activity similarly to PD98059 in retinas of experimental glaucoma rats, while PD98059 also similarly suppressed glial activation, NF-kappa B pathway, NADPH oxidase, and TNF-alpha production. However, PD98059 did not affect RGC survival, apoptotic regulation, or autophagy as NaHS did.CONCLUSIONS. Our study indicated that inhibition of ERK 1/2 pathway might partly contribute to the neuroprotection by H2S in experimental glaucoma; however, it was insufficient to initiate the therapeutic effect on its own.