title: Altered expression of the prion gene in rat astrocyte and neuron cultures treated with prion peptide 106-126.
abstract: Neuronal degeneration and astrogliosis are hallmarks of prion disease. Synthetic prion protein (PrP) peptide 106-126 (PrP106-126) can induce death of neurons and proliferation of astrocytes in vitro and this neurotoxic effect depends on the expression of cellular PrP (PrPC) and is hence believed to be PrP(C) -mediated. To further elucidate the involvement of PrPC in PrP106-126-induced neurotoxicity, we determined the expression of PrP mRNA in primary culture of rat cortical neuron cells, cerebellar granule cells, and astrocytes following treatment with 50 microM of PrP106-126 scrambled PrP106-126 by quantitative real-time RT-PCR. As shown by MTT test, PrP106-126 induced significant death of neuron cells and marked proliferation of astrocytes after 10 days of treatment. Under the same treatment regimens, the level of PrP gene expression was significantly down-regulated in cortical neuron cell cultures and cerebellar granule cell cultures and was up-regulated in astrocyte cultures. The altered PrP gene expression occurred as early as 3 days after the treatment. After 10 days of treatment, while the cultured cortical neurons underwent further apoptosis, their expression of PrP gene started to recover gradually. These findings indicate that PrP 106-126 regulates transcription of the PrP gene and this activity is associated with its neurotoxicity in primary rat neuronal cultures.
authors.affiliation: National Animal Transmissible Spongiform Encephalopathies Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, People's Republic of China.
authors.forename: Zhang-Yong
authors.initials: ZY
authors.lastname: Ning
authors.forename: De-Ming
authors.initials: DM
authors.lastname: Zhao
authors.forename: Hong-Xiang
authors.initials: HX
authors.lastname: Liu
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Yang
authors.forename: Cai-Xia
authors.initials: CX
authors.lastname: Han
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Cui
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Meng
authors.forename: Chang-De
authors.initials: CD
authors.lastname: Wu
authors.forename: Mei-Li
authors.initials: ML
authors.lastname: Liu
authors.forename: Tai-Xiang
authors.initials: TX
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D018920:Coculture Techniques; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D005911:Gliosis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009498:Neurotoxins / Q000633:toxicity*; D010446:Peptide Fragments / Q000235:genetics / Q000633:toxicity*; D018621:PrPC Proteins / Q000096:biosynthesis / Q000235:genetics*; D017096:Prion Diseases / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D011328:Prions / Q000235:genetics / Q000633:toxicity*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D009498:Neurotoxins; D010446:Peptide Fragments; D018621:PrPC Proteins; D011328:Prions; D012333:RNA, Messenger; C082632:prion protein (106-126)