Acute ischemic stroke is a highly prevalent and disabling disease with poor prognosis.Neuronal death is a major feature after a stroke.PANoptosis is a newly reported pattern of cell death,characterized by pyroptosis,a...Acute ischemic stroke is a highly prevalent and disabling disease with poor prognosis.Neuronal death is a major feature after a stroke.PANoptosis is a newly reported pattern of cell death,characterized by pyroptosis,apoptosis,and necroptosis,that plays an important role in the pathophysiological process after ischemic brain injury.However,its precise underlying mechanisms have not yet been fully elucidated.This study aimed to clarify the function of S100 calcium-binding protein A10 in neuronal PANoptosis after ischemic brain damage and to investigate the impact and mechanism of sonic hedgehog and S100 calcium-binding protein A10 on PANoptosis.The results showed that S100 calcium-binding protein A10 was significantly upregulated in both cellular and animal models of ischemic stroke.Knockdown of S100 calcium-binding protein A10 exacerbated PANoptosis and the levels of PANoptosis-related proteins following cerebral ischemia damage.Sonic hedgehog treatment increased S100 calcium-binding protein A10 and inhibited the increase in PANoptosis induced by S100 calcium-binding protein A10 knockdown.The findings suggest that sonic hedgehog intervention mitigated neuronal PANoptosis ensuing from ischemic stroke.The combination of S100 calcium-binding protein A10 and sonic hedgehog demonstrated promise for developing an effective therapy against cerebral ischemic stroke,which would have significant potential for future clinical applications.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82171456(to QY),and 81971229(to QY)the Natural Science Foundation of Chongqing,No.CSTC2021JCYJ-MSXMX0263(to QY)Doctoral Innovation Project of The First Affiliated Hospital of Chongqing Medical University,Nos.CYYY-BSYJSCXXM-202318(to JW)and CYYY-BSYJSCXXM-202327(to HT).
文摘Acute ischemic stroke is a highly prevalent and disabling disease with poor prognosis.Neuronal death is a major feature after a stroke.PANoptosis is a newly reported pattern of cell death,characterized by pyroptosis,apoptosis,and necroptosis,that plays an important role in the pathophysiological process after ischemic brain injury.However,its precise underlying mechanisms have not yet been fully elucidated.This study aimed to clarify the function of S100 calcium-binding protein A10 in neuronal PANoptosis after ischemic brain damage and to investigate the impact and mechanism of sonic hedgehog and S100 calcium-binding protein A10 on PANoptosis.The results showed that S100 calcium-binding protein A10 was significantly upregulated in both cellular and animal models of ischemic stroke.Knockdown of S100 calcium-binding protein A10 exacerbated PANoptosis and the levels of PANoptosis-related proteins following cerebral ischemia damage.Sonic hedgehog treatment increased S100 calcium-binding protein A10 and inhibited the increase in PANoptosis induced by S100 calcium-binding protein A10 knockdown.The findings suggest that sonic hedgehog intervention mitigated neuronal PANoptosis ensuing from ischemic stroke.The combination of S100 calcium-binding protein A10 and sonic hedgehog demonstrated promise for developing an effective therapy against cerebral ischemic stroke,which would have significant potential for future clinical applications.
