title: Increase in phosphorylation of PDK1 and cell survival after acute spinal cord injury.
abstract: 3-Phosphoinositidedependent protein kinase-1 (PDK1), which phosphorylates and activates a group of kinases, plays important roles in cellular metabolism, growth, proliferation and survival. However, the functions of PDK1 in central nervous system (CNS) injury remain an enigma. To elucidate the expressions and possible functions of PDK1 and its phosphorylation in CNS injury and repair, we performed an acute spinal cord injury (SCI) model in adult rats and detected the expression and localization of serine-241 phosphorylated PDK1 (p-PDK1s241). Western blot and immunohistochemistry showed that serine-241 phosphorylated PDK1 (p-PDK1s241) started increasing by 6h after damage and peaked at 12h, then declined to basal levels by 3days after injury. Immunohistochemical staining also revealed subcellular localization changes of p-PDK1s241 staining between nucleus and cytoplasm after injury including neurons and glial cells. Double immunofluorescence labeling suggested that p-PDK1s241 primarily localizes in neurons and oligodendrocytes. It might also be expressed in other glial cells of spinal cord tissues within 2mm from the epicenter at 12h post-injury. Moreover, double staining indicated that p-PDK1s241 and active caspase-3 showed different cellular distributions after SCI. Together with previous reports, we hypothesize that phosphorylation of PDK1 may be associated with cell survival and suggest PDK1 as a novel target for neuroprotection and functional repair in SCI.
authors: Department of Orthopaedics, the Second Affiliated Hospital, Nanjing Medical University, Nanjing 210011, China.
authors: Yi
authors: Y
authors: Zhong
authors: Ye
authors: Y
authors: Huang
authors: Jianhua
authors: J
authors: Cao
authors: Xiang
authors: X
authors: Lu
authors: Meijiang
authors: M
authors: Feng
authors: Gan
authors: G
authors: Shen
authors: Aiguo
authors: A
authors: Shen
authors: Xiaowei
authors: X
authors: Yu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D004195:Disease Models, Animal; D008297:Male; D009474:Neurons / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000503:physiopathology*
chemical_list: C000631434:Pdk1 protein, rat; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3