Hydrogen sulfide protects against endoplasmic reticulum stress and mitochondrial injury in nucleus pulposus cells and ameliorates intervertebral disc degeneration

作者：Xu, Daoliang; Jin, Haiming; Wen, Jianxia; Chen, Jiaoxiang; Chen, Deheng; Cai, Ningyu; Wang, Yongli; Wang, Jianle; Chen, Yu; Zhang, Xiaolei^*; Wang, Xiangyang^*

来源：Pharmacological Research, 2017, 117: 357-369.

DOI：10.1016/j.phrs.2017.01.005

• Hydrogen sulfide
• Intervertebral disc degeneration
• Endoplasmic reticulum stress
• Mitochondrial injury
• Apoptosis

It has been suggested that excessive apoptosis in intervertebral disc cells induced by inflammatory cytokines, such as interleukin (IL) -1p, is related to the process of intervertebral disc degeneration (IVDD). Hydrogen sulfide (H2S), a gaseous signaling molecule, has drawn attention for its anti-apoptosis role in various pathophysiological processes in degenerative diseases. To date, there has been no investigation of the correlation of H2S production and IVDD or of the effects of H2S on IL-1 beta-induced apoptosis in nucleus pulposus (NP) cells. Here, we found that the expression levels of cystathionine beta-synthase (CBS) and cystathionine-gamma-Iyase (CSE), two key enzymes in the generation of H2S, were significantly decreased in human degenerate NP tissues as well as in IL-1 beta-treated NP cells. NaHS (H2S donor) administration showed a protective effect by inhibiting the endoplasmic reticulum (ER) stress response and mitochondrial dysfunction induced by IL-1 beta stimulation in vitro, the effect was related to activation of the PI3K/Akt and ERK1/2 signaling pathways. Suppression of these pathways by specific inhibitors, LY294002 and PD98059, partially reduced the protective effect of NaHS. Moreover, in the percutaneous needle puncture disc degeneration rat tail model, disc degeneration was partially reversed by NaHS administration. Taken together, our results suggest that H2S plays a protective role in IVDD and the underlying mechanism involves PI3K/Akt and ERK1/2 signaling pathways-mediated suppression of ER stress and mitochondrial dysfunction in IL-I beta-induced NP cells.

• 出版日期2017-3
• 单位温州医科大学; 湖州市中心医院