Hydrogen Sulfide Inhibits High Glucose-Induced Neuronal Senescence by Improving Autophagic Flux via Up-regulation of SIRT1
Hydrogen Sulfide Inhibits High Glucose-Induced Neuronal Senescence by Improving Autophagic Flux via Up-regulation of SIRT1
复制标题
硫化氢通过上调 SIRT1 改善自噬通量来抑制高葡萄糖诱导的神经元衰老
DOI：
10.3389/fnmol.2019.00194
复制
发表时间：
2019-08
影响因子：
4.8
通讯作者：
Tang Xiao Qing
中科院分区：
文献类型：
--
作者：
Wu Lei;Chen Ying;Wang Chun Yan;Tang Yi Yun;Huang Hong Lin;Kang Xuan;Li Xiang;Xie Yu Rong;Tang Xiao Qing
高血糖是糖尿病 (DM) 的一个关键特征和危险因素，会导致神经元衰老。硫化氢（H2S）是一种新型神经保护剂。目前的工作是研究 H2S 对高血糖诱导的神经元衰老的潜在影响及其潜在机制。我们发现，H2S 供体 NaHS 可以抑制 HT22 细胞（永生化小鼠海马细胞系）中高葡萄糖 (HG) 诱导的细胞衰老，表现为衰老相关 β-半乳糖苷酶 (SA-β-gal) 阳性细胞数量减少、细胞生长增加以及衰老标记蛋白 p16INK4a 和 p21CIP1 下调。 NaHS 改善了自噬通量，这是通过细胞内自噬体数量的减少以及 HG 暴露的 HT22 细胞中 LC3II/I 和 P62 的上调来判断的。此外，氯喹（CQ）阻断自噬通量显着消除了NaHS对暴露GH的HT22细胞的自噬通量的改善和细胞衰老的抑制，这表明H2S通过促进自噬通量来拮抗HG诱导的神经元衰老。我们还发现，在 HG 暴露的 HT22 细胞中，NaHS 上调了沉默交配型信息调节 2 同源物 1 (SIRT1) 的表达，SIRT1 是一种重要的抗衰老蛋白。此外，sirtinol 对 SIRT1 的抑制逆转了 H2S 对 HG 诱导的自噬通量阻断和 HT22 细胞中细胞衰老的保护作用。这些数据表明，H2S 通过上调 SIRT1 来改善自噬通量，从而保护 HT22 细胞免受 HG 诱导的神经元衰老，表明 H2S 作为高血糖诱导的神经元衰老和神经毒性的潜在治疗策略。
Hyperglycemia, a key characteristic and risk factor for diabetes mellitus (DM), causes neuronal senescence. Hydrogen sulfide (H2S) is a novel neuroprotectant. The present work was to investigate the potential effect of H2S on hyperglycemia-induced neuronal senescence and the underlying mechanisms. We found that NaHS, a donor of H2S, inhibited high glucose (HG)-induced cellular senescence in HT22 cells (an immortalized mouse hippocampal cell line), as evidenced by a decrease in the number of senescence associated-β-galactosidase (SA-β-gal) positive cells, increase in the growth of cells, and down-regulations of senescence mark proteins, p16INK4a and p21CIP1. NaHS improved the autophagic flux, which is judged by a decrease in the amount of intracellular autophagosome as well as up-regulations of LC3II/I and P62 in HG-exposed HT22 cells. Furthermore, blocked autophagic flux by chloroquine (CQ) significantly abolished NaHS-exerted improvement in the autophagic flux and suppression in the cellular senescence of GH-exposed HT22 cells, which indicated that H2S antagonizes HG-induced neuronal senescence by promoting autophagic flux. We also found that NaHS up-regulated the expression of silent mating type information regulation 2 homolog 1 (SIRT1), an important anti-aging protein, in HG-exposed HT22 cells. Furthermore, inhibition of SIRT1 by sirtinol reversed the protection of H2S against HG-induced autophagic flux blockade and cellular senescence in HT22 cells. These data indicated that H2S protects HT22 cells against HG-induced neuronal senescence by improving autophagic flux via up-regulation of SIRT1, suggesting H2S as a potential treatment strategy for hyperglycemia-induced neuronal senescence and neurotoxicity.
登录
查看更多内容
影响因子：
3.7
作者：
Sanokawa-Akakura R;Akakura S;Tabibzadeh S
通讯作者：
Tabibzadeh S
影响因子：
2.4
作者：
Song J;Lee B;Kang S;Oh Y;Kim E;Kim CH;Song HT;Lee JE
通讯作者：
Lee JE
影响因子：
6.1
作者：
Ward R;Ergul A
通讯作者：
Ergul A
影响因子：
--
作者：
Li XN;Chen L;Luo B;Li X;Wang CY;Zou W;Zhang P;You Y;Tang XQ
通讯作者：
Tang XQ
影响因子：
5.4
作者：
Kaur, Navpreet;Kishore, Lalit;Singh, Randhir
通讯作者：
Singh, Randhir