NS8593 inhibits sodium nitroprusside-induced chondrocyte apoptosis by mediating the STING signaling pathway
Rendi Zhu,
Wenjuan Hao,
Shufang Li,
Yong Chen,
Fuli Zhou,
Renpeng Zhou,
Wei Hu
Affiliations
Rendi Zhu
Department of Clinical Pharmacology, The Second Hospital of Anhui Medical University, Hefei, 230601, China; The Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China
Wenjuan Hao
The Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China
Shufang Li
Department of Clinical Pharmacology, The Second Hospital of Anhui Medical University, Hefei, 230601, China
Yong Chen
Department of Clinical Pharmacology, The Second Hospital of Anhui Medical University, Hefei, 230601, China
Fuli Zhou
Department of Clinical Pharmacology, The Second Hospital of Anhui Medical University, Hefei, 230601, China; The Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China
Renpeng Zhou
Department of Clinical Pharmacology, The Second Hospital of Anhui Medical University, Hefei, 230601, China; The Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China; Corresponding author. Department of Clinical Pharmacology, The Second Hospital of Anhui Medical University, Hefei, 230601, China.
Wei Hu
Department of Clinical Pharmacology, The Second Hospital of Anhui Medical University, Hefei, 230601, China; Anhui Provincial Institute of Translational Medicine, Hefei, 230032, China; Corresponding author. Department of Clinical Pharmacology, The Second Hospital of Anhui Medical University, Hefei, 230601, China.
Articular cartilage damage and chondrocyte apoptosis are among the distinguishing features of osteoarthritis. (R)-N-(benzimidazol-2-yl)-1,2,3,4-tetrahydro-1-naphtylamine (NS8593) is a transient receptor potential cation channel subfamily M member 7 (TRPM7) channel inhibitor and was initially considered a potent inhibitor of small-conductance Ca2+-activated K+ channels(SK1-3 or KCa2.1–2.3 channels). Since SK is one of the targets for atrial fibrillation therapy, several studies have been conducted using NS8593 and it has been shown to be effective in improving atrial fibrillation in rats, dogs and horses. Recently, inhibition of TRPM7 has been reported to alleviate articular cartilage destruction. However, the role and mechanism of NS8593 on articular chondrocyte damage is unknown. The purpose of this study was to investigate the effect and mechanism of NS8593 on sodium nitroprusside (SNP)-induced chondrocyte apoptosis in vitro. The results showed that SNP decreased cell viability and induced chondrocyte apoptosis. NS8593 dose-dependently inhibited the SNP-induced decrease in cell viability and reduced chondrocyte apoptosis. In addition, SNP stimulation significantly increased the phosphorylation level of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING), and NS8593 treatment partially reversed the alteration of STING phosphorylation level. Treatment with the STING inhibitor H-151 inhibited SNP-induced chondrocyte apoptosis. These results suggest that NS8593 may inhibit SNP-induced chondrocyte apoptosis by suppressing the STING signaling pathway.
