title: CaMKII activates ASK1 to induce apoptosis of spinal astrocytes under oxygen-glucose deprivation.
abstract: Calcium/calmodulin-dependent protein kinase II (CaMKII) is a ubiquitous, structurally complex multifunctional protein serine/threonine kinase that plays an important role in cell apoptosis via linking the ER stress and mitochondrial apoptosis pathways. Recently, CaMKII has been correlated with apoptosis signal-regulating kinase 1 (ASK1) activity and the ASK1-dependent apoptosis pathway through the direct phosphorylation of Thr845 of ASK1. The specific role of CaMKII in hypoxia-reoxygenation (H/R)-induced spinal astrocyte apoptosis, however, remains unclear. In this study, we investigated the effects of CaMKIIγ (an isoform of CaMKII) on spinal astrocyte apoptosis using an in vitro oxygen-glucose deprivation (OGD/R) model which mimics hypoxic/ischemic conditions in vivo. OGD/R increased cell death and the activation of CaMKII. Deletion of CaMKIIγ results in the reduced activation of CaMKII and apoptosis in astrocytes under OGD/R conditions. Notably, the deletion of CaMKIIγ induced ASK1 phosphorylation at Thr845 in astrocytes. The activation of JNK and p38 and the downstream effect of ASK1 were also reduced. These data suggest that CaMKIIγ is required for the CaMKII-dependent regulation of ASK1, affecting the apoptosis of a biologically important cell type under spinal cord injury.
authors.affiliation: Department of Orthopedic Surgery, Jinling Hospital, 305# East Zhongshan Road, Nanjing 210002, Jiangsu, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Jianning
authors.initials: J
authors.lastname: Zhao
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Chang
authors.forename: Guodong
authors.initials: G
authors.lastname: Guo
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D017353:Gene Deletion; D005947:Glucose / Q000172:deficiency*; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism*; D010100:Oxygen / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013116:Spinal Cord / Q000473:pathology*
chemical_list: D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D048848:MAP Kinase Kinase Kinase 5; D053148:Caspase 3; D005947:Glucose; D010100:Oxygen; D000111:Acetylcysteine