Medroxyprogesterone promotes neuronal survival after cerebral ischemic stroke by inhibiting PARthanatos DOI Creative Commons

Chang-Ling Yue,

Yanfei Ding, Meng Chen

и другие.

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Фев. 13, 2025

Introduction Cerebral ischemic stroke (CIS) is caused by the interruption of cerebral blood circulation due to thrombosis or embolism and second-leading cause mortality worldwide. The neuronal death motor dysfunction resulting from CIS are primarily attributed induction PARthanatos in neurons at site ischemia. Blocking parthanatos a promising treatment for CIS. Methods effect medroxyprogesterone on vitro was examined CCK8 assay flow cytometry target protein then identified series assays, including western blotting, immunofluorescence, cell thermal shift molecular docking. Subsequently, efficacy evaluated FJC staining. Results In our study, able block occurrence Hela cells induced MNNG. PARP-1 activity did not change after but prevented MNNG-induced apoptosis inducing factor (AIF) release mitochondria improving stability phosphorylated extracellular signal-regulated kinase (ERK). vivo, significantly reduces mouse models inhibiting PARthanatos. Conclusion Our findings indicate that effectively inhibits affecting PARP-1, directly binding ERK stabilizes active ERK, thereby AIF translocation. Furthermore, shows potential as neuroprotective agent patients with CIS, potentially enhancing post-stroke recovery reducing societal burdens.

Язык: Английский

Medroxyprogesterone promotes neuronal survival after cerebral ischemic stroke by inhibiting PARthanatos DOI Creative Commons

Chang-Ling Yue,

Yanfei Ding, Meng Chen

и другие.

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Фев. 13, 2025

Introduction Cerebral ischemic stroke (CIS) is caused by the interruption of cerebral blood circulation due to thrombosis or embolism and second-leading cause mortality worldwide. The neuronal death motor dysfunction resulting from CIS are primarily attributed induction PARthanatos in neurons at site ischemia. Blocking parthanatos a promising treatment for CIS. Methods effect medroxyprogesterone on vitro was examined CCK8 assay flow cytometry target protein then identified series assays, including western blotting, immunofluorescence, cell thermal shift molecular docking. Subsequently, efficacy evaluated FJC staining. Results In our study, able block occurrence Hela cells induced MNNG. PARP-1 activity did not change after but prevented MNNG-induced apoptosis inducing factor (AIF) release mitochondria improving stability phosphorylated extracellular signal-regulated kinase (ERK). vivo, significantly reduces mouse models inhibiting PARthanatos. Conclusion Our findings indicate that effectively inhibits affecting PARP-1, directly binding ERK stabilizes active ERK, thereby AIF translocation. Furthermore, shows potential as neuroprotective agent patients with CIS, potentially enhancing post-stroke recovery reducing societal burdens.

Язык: Английский

Процитировано

0