title: Up-regulation of c-Fos associated with neuronal apoptosis following intracerebral hemorrhage.
abstract: The proto-oncogene c-Fos is an important member of the activating protein 1 (AP-1) transcription complex involved in major cellular functions such as transformation, proliferation, differentiation, and apoptosis. The expression of c-Fos is very tightly regulated and responses rapidly and transiently to a plethora of apoptotic stimuli. However, it is still unclear how c-Fos functions on neuronal activities following intracerebral hemorrhage (ICH). In the present studies, we uncovered that the up-regulation of c-Fos is related to neuronal apoptosis following ICH probably via FasL/Fas apoptotic pathway. From the results of Western blot and immunohistochemistry, we obtained that c-Fos is significantly up-regulated surrounding the hematoma following ICH and co-locates with active caspase-3 in the neurons. Besides, electrophoretic mobility shift assay exhibits high AP-1 DNA-binding activities in ICH groups due to the increase of c-Fos expression. In addition, there are concomitant up-regulation of Fas ligand (FasL), which is the target protein of AP-1, Fas, active caspase-8, and active caspase-3 in vivo and in vitro studies. What is more, our in vitro study showed that using c-Fos-specific RNA interference in primary cortical neurons, the expression of FasL and active caspase-3 are suppressed. Thus, our results indicated that c-Fos might exert its pro-apoptotic function on neuronal apoptosis following ICH.
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, 220 Handan Rd, Shanghai, 200433, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Neurology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China.
authors.forename: Jiabing
authors.initials: J
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, 220 Handan Rd, Shanghai, 200433, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, 220 Handan Rd, Shanghai, 200433, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, 220 Handan Rd, Shanghai, 200433, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, 220 Handan Rd, Shanghai, 200433, China.
authors.forename: Huili
authors.initials: H
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, 220 Handan Rd, Shanghai, 200433, China. kkhuo@fudan.edu.cn.
authors.forename: Keke
authors.initials: K
authors.lastname: Huo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002478:Cells, Cultured; D002543:Cerebral Hemorrhage / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D016760:Proto-Oncogene Proteins c-fos