Nrf2 signaling activation by a small molecule activator compound 16 inhibits hydrogen peroxide-induced oxidative injury and death in osteoblasts

• DOI: 10.1038/s41420-022-01146-7
• Publication Date: 2022-08-08T12:02:59Z
• Authors: Jing-wei Zhao; Pei-jun Tang; Zhen-tao Zhou; Gang Xu; Quan Li; Ke-ran Li; Yue-huan Zheng
• Keywords: KEAP1; Cytoprotection

We explored the potential activity of compound 16 (Cpd16), a novel small molecule Nrf2 activator, in hydrogen peroxide (H2O2)-stimulated osteoblasts. In primary murine/human osteoblasts and MC3T3-E1 murine osteoblastic cells, Cpd16 treatment at micro-molar concentrations caused disassociation Keap1-Nrf2 cascade activation. induced stabilization protein its nuclear translocation, thereby increasing antioxidant response elements (ARE) reporter genes transcription human Significantly, mitigated oxidative injury H2O2-stimulited H2O2-provoked apoptosis as well programmed necrosis were significantly alleviated by activator. Cpd16-induced activation protection stronger than other known activators. Dexamethasone- nicotine-caused stress death attenuated well. osteoblast cytoprotection was abolished short hairpin RNA or knockout, but mimicked Keap1 knockout. Cys151S mutation against H2O2. Importantly, weekly administration largely ameliorated trabecular bone loss ovariectomy mice. Together, alleviates H2O2-induced activating cascade.