title: Cyclic AMP response element modulator-1 (CREM-1) involves in neuronal apoptosis after traumatic brain injury.
abstract: The cyclic AMP response element-binding protein (CREB) family can regulate biological functions of various types of cells by forming homo- or heterodimers to bind the target DNA sequences; it plays an essential role in individual neuronal function and entire neuronal circuits. One attractive activity of the CREB family is regulating the transcription of apoptosis-suppressor gene bcl-2. Cyclic AMP response element modulator-1 (CREM-1) is one member of the family with limited acquaintance. To investigate whether CREM-1 is involved in central nervous system injury and repair, we performed an acute traumatic brain injury (TBI) model in adult rats. Western blot analysis and immunohistochemistry showed a significant upregulation of CREM-1 in ipsilateral peritrauma cortex. Immunofluorescent labeling indicated that CREM-1 was localized mainly in the nuclei of neurons; co-localization of CREM-1 and active-caspase-3 in the ipsilateral cortex suggested that CREM-1 might participate in neuronal apoptosis. To further investigate the function of CREM-1, a neuronal cell line PC12 was employed to establish an apoptosis model. We analyzed the association of CREM-1 with p-CREB on PC12 cells by Western blot, immunofluorescent labeling, and co-immunoprecipitation. The result implied that the association of CREM-1 with p-CREB was enhanced in apoptotic cells. Additionally, knocking CREM-1 down with siRNA demonstrated the probable pro-apoptotic role played by CREM-1 in neuronal apoptosis. Together with our data, we hypothesized that CREM-1 might play an important role in regulating neuronal death after TBI by interacting with CREB.
authors.affiliation: Department of Neurology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, People's Republic of China, 226001.
authors.forename: Xinmin
authors.initials: X
authors.lastname: Wu
authors.forename: Wei
authors.initials: W
authors.lastname: Jin
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Liu
authors.forename: Hongran
authors.initials: H
authors.lastname: Fu
authors.forename: Peipei
authors.initials: P
authors.lastname: Gong
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.forename: Gang
authors.initials: G
authors.lastname: Cui
authors.forename: Yaohui
authors.initials: Y
authors.lastname: Ni
authors.forename: Kaifu
authors.initials: K
authors.lastname: Ke
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Gao
authors.forename: Yilu
authors.initials: Y
authors.lastname: Gao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001930:Brain Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051786:Cyclic AMP Response Element Modulator / Q000235:genetics / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C497412:Crem protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D051786:Cyclic AMP Response Element Modulator