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Báo cáo khoa học: Control of transferrin expression by b-amyloid through the CP2 transcription factor

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Control of transferrin expression by b-amyloid through the CP2 transcription factor Sang-Min Jang1,*, Jung-Woong Kim1,*, Chul-Hong Kim1, Joo-Hee An1, Eun-Jin Kang1, Chul Geun Kim2, Hyun-Jung Kim3 and Kyung-Hee Choi1 1 Department of Life Science (BK21 Program), College of Natural Sciences, Chung-Ang University, Seoul, Korea 2 Department of Life Science and Research Institute for Natural Sciences, Hanyang University, Seoul, Korea 3 College of Pharmacy, Chung-Ang University, Seoul, Korea Keywords Alzheimer’s disease; CP2; iron homeostasis; oxidative stress; transferrin Correspondence K.-H. Choi, Department of Life Science (BK21 Program), College of Natural Sciences, Chung-Ang University, 221 Heuksuk Dong, Dongjak Ku, Seoul 156-756, South Korea Fax: +82 2. | Control of transferrin expression by p-amyloid through the CP2 transcription factor Sang-Min Jang1 z Jung-Woong Kim1 z Chul-Hong Kim1 Joo-Hee An1 Eun-Jin Kang1 Chul Geun Kim2 Hyun-Jung Kim3 and Kyung-Hee Choi1 1 Department of Life Science BK21 Program College of NaturalSciences Chung-Ang University Seoul Korea 2 Department of Life Science and Research Institute for NaturalSciences Hanyang University Seoul Korea 3 College of Pharmacy Chung-Ang University Seoul Korea Keywords Alzheimer s disease CP2 iron homeostasis oxidative stress transferrin Correspondence K.-H. Choi Department of Life Science BK21 Program College of Natural Sciences Chung-Ang University 221 Heuksuk Dong Dongjak Ku Seoul156-756 South Korea Fax 82 2 824 7302 Tel 82 2 820 5209 E-mail khchoi@cau.ac.kr These authors contributed equally to this work The authors declare no conflict of interest Received 16 February 2010 revised 28 June 2010 accepted 12 July 2010 doi 10.1111 j.1742-4658.2010.07801.x Accumulation of p-amyloid protein Ab is one of the most important pathological features of Alzheimer s disease. Although Ap induces neurodegeneration in the cortex and hippocampus through several molecular mechanisms few studies have evaluated the modulation of transcription factors during Ap-induced neurotoxicity. Therefore in this study we investigated the transcriptional activity of transcription factor CP2 in neuronal damage mediated by Ap Ap1-42 and Ap25 35 . An unbiased motif search of the transferrin promoter region showed that CP2 binds to the transferrin promoter an iron-regulating protein and regulates transferrin transcription. Ectopic expression of CP2 led to increased transferrin expression at both the mRNA and protein levels whereas knockdown of CP2 down-regulated transferrin mRNA and protein expression. Moreover CP2 trans-activated transcription of a transferrin reporter gene. An electrophoretic mobility shift assay and a chromatin immunoprecipitation assay showed that CP2 binds to the .

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