Defective ferritinophagy was involved in high glucose-induced neuron oxidative damage in ND7/23 cells.
Source: PubMed, NCBI / U.S. National Library of Medicine
Diabetic peripheral neuropathy (DPN) is associated with oxidative stress induced by hyperglycemia. Ferritinophagy is critical for maintaining intracellular iron homeostasis and oxidative injury induced by iron overload. However, the relationship between ferritinophagy and high glucose-induced neuronal oxidative damage has not yet been explored. In this study, we established a model of high glucose-induced oxidative damage in ND7/23 cells. ND7/23 cells treated with rapamycin or bafilomycin A1 were used to investigate changes in ferritinophagy, while cells transfected with NCOA4-siRNA were employed to explore the role of ferritinophagy in this process. The results revealed that hyperglycemia inhibited the viability of ND7/23 cells, increased intracellular iron overload, ROS accumulation, and triggered abnormal ferritinophagy characterized by elevated ferritin, NCOA4, and p62 protein levels, together with a reduced LC3II/I ratio. Activation of ferritinophagy with rapamycin alleviated high glucose-induced iron overload and oxidative injury in ND7/23 cells. In contrast, inhibition of autophagy by bafilomycin A1 exacerbated these high glucose-mediated damages. Intriguingly, we found that NCOA4 knockdown improved high glucose-impaired ferritinophagy, reduced intracellular iron concentration, and mitigated oxidative damage in ND7/23 cells treated with high glucose. In conclusion, we conclude that high glucose inhibits ferritinophagy, disrupts iron h
Abstract
Diabetic peripheral neuropathy (DPN) is associated with oxidative stress induced by hyperglycemia. Ferritinophagy is critical for maintaining intracellular iron homeostasis and oxidative injury induced by iron overload. However, the relationship between ferritinophagy and high glucose-induced neuronal oxidative damage has not yet been explored. In this study, we established a model of high glucose-induced oxidative damage in ND7/23 cells. ND7/23 cells treated with rapamycin or bafilomycin A1 were used to investigate changes in ferritinophagy, while cells transfected with NCOA4-siRNA were employed to explore the role of ferritinophagy in this process. The results revealed that hyperglycemia inhibited the viability of ND7/23 cells, increased intracellular iron overload, ROS accumulation, and triggered abnormal ferritinophagy characterized by elevated ferritin, NCOA4, and p62 protein levels, together with a reduced LC3II/I ratio. Activation of ferritinophagy with rapamycin alleviated high glucose-induced iron overload and oxidative injury in ND7/23 cells. In contrast, inhibition of autophagy by bafilomycin A1 exacerbated these high glucose-mediated damages. Intriguingly, we found that NCOA4 knockdown improved high glucose-impaired ferritinophagy, reduced intracellular iron concentration, and mitigated oxidative damage in ND7/23 cells treated with high glucose. In conclusion, we conclude that high glucose inhibits ferritinophagy, disrupts iron homeostasis, thereby leading to intracellular iron accumulation and neuron oxidative stress injury in ND7/23 cells. Our results may provide novel perspectives and potential strategies for the prevention and treatment of high glucose-induced oxidative damage.