title: X-ray irradiation accelerates senescence in hippocampal neural stem/progenitor cells via caspase-1 activation.
abstract: Despite the effectiveness in controlling the progression of brain tumors, cranial irradiation often causes neuropsychological deficits in cancer survivors. Inflammation is considered a major cause of tissue injury from irradiation. The caspase-1 activation complexes (inflammasomes) can facilitate caspase-1 and IL-1β processing, which amplifies the inflammatory response. In the present study we examined whether caspase-1 activation contributes to irradiation-induced damage to neural stem and progenitor cells (NSPCs). We found that X-ray irradiation induced activation of caspase-1 in NSPCs in vitro and in vivo. Next, using a caspase-1 inhibitor (Ac-YVAD-CMK) to block caspase-1 activation in vitro and in vivo, we further demonstrated that X-ray irradiation may inhibit proliferation, induce senescence of NSPCs through caspase-1 activation. Together, our results suggest that caspase-1 activation is involved in irradiation-induced damage to NSPCs.
authors.affiliation: Department of Neurosurgery, The Fourth People's Hospital of Jinan city, Jinan 250012, China. Electronic address: litao961@126.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Brain Science Research Institute of Shandong University, Jinan 250012, China; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan 250012, China.
authors.forename: Lianling
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Brain Science Research Institute of Shandong University, Jinan 250012, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Brain Science Research Institute of Shandong University, Jinan 250012, China. Electronic address: ns3000@126.com.
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D020170:Caspase 1 / Q000378:metabolism*; D061945:Caspase Inhibitors / Q000494:pharmacology; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000528:radiation effects*; D004789:Enzyme Activation; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D015854:Up-Regulation
chemical_list: D061945:Caspase Inhibitors; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D020170:Caspase 1
keywords: Caspase-1; Irradiation; NSPCs; Senescence