{"title":"促红细胞生成素通过调节草履虫自噬对麻醉诱导的神经毒性的神经保护作用","authors":"Bon-Wook Koo, Hyun-Jung Shin, Sooyoung Jeon, Jung Hyun Bang, Sang-Hwan Do, Hyo-Seok Na","doi":"10.4097/kja.23789","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The anti-oxidative, anti-inflammatory, and anti-apoptotic effects of erythropoietin may provide neuroprotective effects. Erythropoietin also modulates autophagy signaling that may play a role in anesthesia-induced neurotoxicity (AIN). Herein, we investigated whether AIN can be attenuated by the neuroprotective effect of erythropoietin in the Caenorhabditis elegans (C. elegans).</p><p><strong>Methods: </strong>Synchronized worms were divided into the control, Iso, EPO, and EPO-Iso groups. The chemotaxis index (CI) was evaluated when they reached the young adult stage. The lgg-1::GFP-positive puncta per seam cell were used to determine the autophagic events. The erythropoietin-mediated pathway of autophagy was determined by measuring the genetic expression level of let-363, bec-1, atg-7, atg-5, and lgg-3.</p><p><strong>Results: </strong>Increased lgg-1::GFP puncta were observed in the Iso, EPO, and EPO-Iso groups. In the Iso group, only the let-363 level decreased significantly as compared to that in the control group (P = 0.009). bec-1 (P < 0.001), atg-5 (P = 0.012), and lgg-3 (P < 0.001) were expressed significantly more in the EPO-Iso group than in the Iso groups. Repeated isoflurane exposure during development decreased the CI. Erythropoietin could restore the decreased CI by isoflurane significantly in the EPO-Iso group.</p><p><strong>Conclusions: </strong>Erythropoietin showed neuroprotective effects against AIN and modulated the autophagic pathway in C. elegans. This experimental evidence of erythropoietin-related neuroprotection against AIN may be correlated with the induced autophagic degradation process that was sufficient for handling enhanced autophagy induction in erythropoietin-treated worms.</p>","PeriodicalId":17855,"journal":{"name":"Korean Journal of Anesthesiology","volume":null,"pages":null},"PeriodicalIF":4.2000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11150124/pdf/","citationCount":"0","resultStr":"{\"title\":\"Neuroprotective effect of erythropoietin on anesthesia-induced neurotoxicity through the modulation of autophagy in Caenorhabditis elegans.\",\"authors\":\"Bon-Wook Koo, Hyun-Jung Shin, Sooyoung Jeon, Jung Hyun Bang, Sang-Hwan Do, Hyo-Seok Na\",\"doi\":\"10.4097/kja.23789\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The anti-oxidative, anti-inflammatory, and anti-apoptotic effects of erythropoietin may provide neuroprotective effects. Erythropoietin also modulates autophagy signaling that may play a role in anesthesia-induced neurotoxicity (AIN). Herein, we investigated whether AIN can be attenuated by the neuroprotective effect of erythropoietin in the Caenorhabditis elegans (C. elegans).</p><p><strong>Methods: </strong>Synchronized worms were divided into the control, Iso, EPO, and EPO-Iso groups. The chemotaxis index (CI) was evaluated when they reached the young adult stage. The lgg-1::GFP-positive puncta per seam cell were used to determine the autophagic events. The erythropoietin-mediated pathway of autophagy was determined by measuring the genetic expression level of let-363, bec-1, atg-7, atg-5, and lgg-3.</p><p><strong>Results: </strong>Increased lgg-1::GFP puncta were observed in the Iso, EPO, and EPO-Iso groups. In the Iso group, only the let-363 level decreased significantly as compared to that in the control group (P = 0.009). bec-1 (P < 0.001), atg-5 (P = 0.012), and lgg-3 (P < 0.001) were expressed significantly more in the EPO-Iso group than in the Iso groups. Repeated isoflurane exposure during development decreased the CI. Erythropoietin could restore the decreased CI by isoflurane significantly in the EPO-Iso group.</p><p><strong>Conclusions: </strong>Erythropoietin showed neuroprotective effects against AIN and modulated the autophagic pathway in C. elegans. This experimental evidence of erythropoietin-related neuroprotection against AIN may be correlated with the induced autophagic degradation process that was sufficient for handling enhanced autophagy induction in erythropoietin-treated worms.</p>\",\"PeriodicalId\":17855,\"journal\":{\"name\":\"Korean Journal of Anesthesiology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2024-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11150124/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Korean Journal of Anesthesiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.4097/kja.23789\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/2/15 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"ANESTHESIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Korean Journal of Anesthesiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4097/kja.23789","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/2/15 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ANESTHESIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景:促红细胞生成素的抗氧化、抗炎和抗凋亡作用可能具有神经保护作用。红细胞生成素还能调节自噬信号,而自噬信号可能在麻醉诱导的神经毒性(AIN)中发挥作用。在此,我们研究了红细胞生成素的神经保护作用是否可减轻优雅鼠(C. elegans)的 AIN:方法:将同步化蠕虫分为对照组、Iso 组、EPO 组和 EPO-Iso 组。方法:将同步蠕虫分为对照组、Iso组、EPO组和EPO-Iso组,在它们达到幼虫期时评估趋化指数(CI)。用每个接缝细胞中的 lgg-1::GFP 阳性点来确定自噬事件。通过测量 let-363、bec-1、atg-7、atg-5 和 lgg-3 的基因表达水平,确定了促红细胞生成素介导的自噬途径:结果:在Iso组、EPO组和EPO-Iso组观察到lgg-1::GFP点的增加。Bec-1(P<0.001)、atg-5(P<0.012)和 lgg-3(P<0.001)在 EPO-Iso 组的表达明显高于 Iso 组。发育过程中反复暴露于异氟醚会降低 CI。在EPO-Iso组中,红细胞生成素可明显恢复异氟醚导致的CI下降:结论:红细胞生成素具有抗 AIN 的神经保护作用,并能调节秀丽隐杆线虫的自噬途径。这一与促红细胞生成素相关的抗 AIN 神经保护作用的实验证据可能与诱导的自噬降解过程有关,该过程足以处理促红细胞生成素处理蠕虫中增强的自噬诱导。
Neuroprotective effect of erythropoietin on anesthesia-induced neurotoxicity through the modulation of autophagy in Caenorhabditis elegans.
Background: The anti-oxidative, anti-inflammatory, and anti-apoptotic effects of erythropoietin may provide neuroprotective effects. Erythropoietin also modulates autophagy signaling that may play a role in anesthesia-induced neurotoxicity (AIN). Herein, we investigated whether AIN can be attenuated by the neuroprotective effect of erythropoietin in the Caenorhabditis elegans (C. elegans).
Methods: Synchronized worms were divided into the control, Iso, EPO, and EPO-Iso groups. The chemotaxis index (CI) was evaluated when they reached the young adult stage. The lgg-1::GFP-positive puncta per seam cell were used to determine the autophagic events. The erythropoietin-mediated pathway of autophagy was determined by measuring the genetic expression level of let-363, bec-1, atg-7, atg-5, and lgg-3.
Results: Increased lgg-1::GFP puncta were observed in the Iso, EPO, and EPO-Iso groups. In the Iso group, only the let-363 level decreased significantly as compared to that in the control group (P = 0.009). bec-1 (P < 0.001), atg-5 (P = 0.012), and lgg-3 (P < 0.001) were expressed significantly more in the EPO-Iso group than in the Iso groups. Repeated isoflurane exposure during development decreased the CI. Erythropoietin could restore the decreased CI by isoflurane significantly in the EPO-Iso group.
Conclusions: Erythropoietin showed neuroprotective effects against AIN and modulated the autophagic pathway in C. elegans. This experimental evidence of erythropoietin-related neuroprotection against AIN may be correlated with the induced autophagic degradation process that was sufficient for handling enhanced autophagy induction in erythropoietin-treated worms.