Emilia Lekholm1,2, Mikaela M Ceder3, Erica C Forsberg3, Helgi B Schiöth4,5, Robert Fredriksson3. 1. Functional Pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden. Emilia.Lekholm@farmbio.uu.se. 2. Molecular Neuropharmacology, Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden. Emilia.Lekholm@farmbio.uu.se. 3. Molecular Neuropharmacology, Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden. 4. Functional Pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden. 5. Institute for Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, Moscow, Russia.
Abstract
BACKGROUND: The synaptic vesicle glycoprotein 2 (SV2) family is essential to the synaptic machinery involved in neurotransmission and vesicle recycling. The isoforms SV2A, SV2B and SV2C are implicated in neurological diseases such as epilepsy, Alzheimer's and Parkinson's disease. Suitable cell systems for studying regulation of these proteins are essential. Here we present gene expression data of SV2A, SV2B and SV2C in two human neuroblastoma cell lines after differentiation. METHODS: Human neuroblastoma cell lines SiMa and IMR-32 were treated for seven days with growth supplements (B-27 and N-2), all-trans-retinoic acid (ATRA) or vasoactive intestinal peptide (VIP) and gene expression levels of SV2 and neuronal targets were analyzed. RESULTS: The two cell lines reacted differently to the treatments, and only one of the three SV2 isoforms was affected at a time. SV2B and choline O-acetyltransferase (CHAT) expression was changed in concert after growth supplement treatment, decreasing in SiMa cells while increasing in IMR-32. ATRA treatment resulted in no detected changes in SV2 expression in either cell line while VIP increased both SV2C and dopamine transporter (DAT) in IMR-32 cells. CONCLUSION: The synergistic expression patterns between SV2B and CHAT as well as between SV2C and DAT mirror the connectivity between these targets found in disease models and knock-out animals, although here no genetic alteration was made. These cell lines and differentiation treatments could possibly be used to study SV2 regulation and function.
BACKGROUND: The synaptic vesicle glycoprotein 2 (SV2) family is essential to the synaptic machinery involved in neurotransmission and vesicle recycling. The isoforms SV2A, SV2B and SV2C are implicated in neurological diseases such as epilepsy, Alzheimer's and Parkinson's disease. Suitable cell systems for studying regulation of these proteins are essential. Here we present gene expression data of SV2A, SV2B and SV2C in two humanneuroblastoma cell lines after differentiation. METHODS:Humanneuroblastoma cell lines SiMa and IMR-32 were treated for seven days with growth supplements (B-27 and N-2), all-trans-retinoic acid (ATRA) or vasoactive intestinal peptide (VIP) and gene expression levels of SV2 and neuronal targets were analyzed. RESULTS: The two cell lines reacted differently to the treatments, and only one of the three SV2 isoforms was affected at a time. SV2B and choline O-acetyltransferase (CHAT) expression was changed in concert after growth supplement treatment, decreasing in SiMa cells while increasing in IMR-32. ATRA treatment resulted in no detected changes in SV2 expression in either cell line while VIP increased both SV2C and dopamine transporter (DAT) in IMR-32 cells. CONCLUSION: The synergistic expression patterns between SV2B and CHAT as well as between SV2C and DAT mirror the connectivity between these targets found in disease models and knock-out animals, although here no genetic alteration was made. These cell lines and differentiation treatments could possibly be used to study SV2 regulation and function.
Entities:
Keywords:
Differentiation; Neuroblastoma; SV2A; SV2B; SV2C; Synaptic vesicle protein
Authors: K M Crowder; J M Gunther; T A Jones; B D Hale; H Z Zhang; M R Peterson; R H Scheller; C Chavkin; S M Bajjalieh Journal: Proc Natl Acad Sci U S A Date: 1999-12-21 Impact factor: 11.205