| Autor: |
Jamil Nehme, Lina Mesilmany, Valerio Farfariello, Marta Varela-Eirin, Yao Lin, Mariana Gaya Costa, Marc Seelen, Jan-Luuk Hillebrands, Harry van Goor, Raja Saab, Natacha Prevarskaya, Haidar Akl, Marco Demaria |
| Rok vydání: |
2023 |
| DOI: |
10.21203/rs.3.rs-2672861/v1 |
| Popis: |
Excessive amounts of Reactive oxygen species (ROS) lead to macromolecular damage and pathological sequelae. The mechanisms regulating oxidative stress-induced cell fate decision and their manipulation for improving repair remain poorly understood. Here, we show that cells exposed to high oxidative stress enter a PARP1-mediated necrosis, and that blocking PARP1 activation promotes a senescence state. We demonstrate that the switch from death to senescence depends on reducing mitochondrial Ca2+ overload as a consequence of retaining the hexokinase HKII into mitochondria. In a mouse model of kidney ischemia/reperfusion damage, PARP1 inhibition lowers necrosis and increases senescence at the injury site, leading to improved recovery from acute damage. PARP1 activity is essential to promote necrosis in high oxidative environments, and its inhibition alleviates the detriment of acute tissue damage by promoting senescence. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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