Electrospray-ionization mass spectrometric (ESIMS) studies of several A007 prodrugs in aqueous cyclomaltohexaose (alpha-cyclodextrin, alpha-CD), cyclomaltoheptaose (beta-cyclodextrin, beta-CD), and cyclomaltooctaose (gamma-cyclodextrin, gamma-CD) were performed. The acetic acid derivative of A007 should metabolize in vivo before becoming the A007 prodrug, while on the other hand, the glycine-modified A007 prodrug has surfactant-like physical properties and slowly hydrolyzed in the aqueous cyclodextrins by releasing free A007. ESIMS studies give insight into the process of prodrug hydrolysis in the presence of cyclodextrins and, hence, the influence of cyclodextrins on the timely release of the A007 prodrug. Formation of various molecular aggregates and cyclodextrin inclusion complexes of A007 prodrugs and their hydrolyzed products was demonstrated by ESIMS.

01 Jul 2003·Journal of Neuroscience ResearchQ3 · MEDICINE

Regulation of CNS glial phenotypes in N20.1 cells

Q3 · MEDICINE

Article

Author: Joyce A. Benjamins ; Diane M. Studzinski

AbstractThe N20.1 oligodendroglial cell line, immortalized with SV40 T antigen, simultaneously expresses oligodendroglial markers and glial fibrillary acidic protein (GFAP), an astroglial marker. This study examines the plasticity of N20.1 cells with regard to GFAP expression, and its relationship to expression of SV40 T antigen, p53, and a novel nuclear antigen detected by the A007 monoclonal antibody. Marked changes occur in GFAP levels and cell morphology when N20.1 cells are switched from the permissive temperature (34°C) to the non‐permissive temperature (39°C), and with cyclic AMP elevation at 39°C. At 34°C, levels of GFAP are high; when cells are switched to 39°C, GFAP levels decrease significantly, then increase slightly when forskolin is added. At both temperatures, the cells display feathery GFAP immunostaining. When forskolin is added at 39°C, however, cells display bright fibrous GFAP staining in elongated processes. The changes in GFAP were compared to changes in T antigen and p53. As expected, the decrease in T antigen at 39°C was accompanied by movement of p53 from the nucleus to cytoplasm. Total p53 levels did not change, however, and forskolin did not alter the respective distribution or levels of p53 at either temperature. At both temperatures, the cell bodies and processes show internal expression of sulfatide, as demonstrated with the O4, Sulph I, and A007 antibodies. We show, for the first time, abundant nuclear immunoreactivity with the A007 monoclonal antibody in the N20.1 cells. This nuclear reactivity is seen at 34°C, but not at 39°C, similar to p53, and is not detected with the other sulfatide antibodies. Double‐label immunostaining shows that the nuclear A007 immunoreactivity is co‐localized in nuclear structures with T antigen and p53 at 34°C, but is not found in every nucleus containing these antigens. We conclude that regulation of GFAP expression and morphology in N20.1 cells is dependent on a combination of T antigen expression and level of cAMP and may be related to regulation of p53 and the A007 nuclear antigen. © 2003 Wiley‐Liss, Inc.

15 Mar 2001·Microscopy Research and TechniqueQ4 · ENGINEERING & TECHNOLOGY

Re‐evaluation of nestin as a marker of oligodendrocyte lineage cells

Q4 · ENGINEERING & TECHNOLOGY

Article

Author: Carmen Guaza ; José Miguel Vela ; Eduardo Molina-Holgado ; Guillermina Almazán

AbstractMaturation of oligodendrocyte progenitors (O2A) is characterized by morphological changes and the sequential expression of specific antigens leading to the formation of myelin membrane. Monoclonal antibodies A2B5, A007, anti‐vimentin, and anti‐galactocerebroside, recognize oligodendroglia at different stages of development. The neuroepithelial precursor marker nestin is also expressed by the oligodendroglial lineage; we have used enriched populations of progenitors isolated from neonatal rat brain cultures to further examine the cellular distribution of this intermediate filament protein. The phenotypic distribution of nestin positive cells among the oligodendrocyte lineage showed that 65% reacted with A2B5, whereas only 5% were A007+, and 4% galactocerebroside+. The remaining 25% of the cells were not labeled and had small cellular bodies devoid of processes, characteristic of the pre‐O2A progenitor. Further analysis of the nestin+ population showed that the majority of the cells were also vimentin+. Antibody‐dependent complement mediated cytolysis of A2B5+ (O2A cells) and galactocerebroside+ (mature oligodendrocytes) cells left a population of nestin+ cells that were induced to proliferate in the presence of growth factors and to differentiate into A2B5+ and galactocerebroside+ cells. Proliferating cells maintained in the presence of platelet‐derived growth factor or basic fibroblast growth factor retained nestin expression along with A2B5. By contrast, in serum‐free medium nestin expression decreased while postmitotic cells acquired A007 and galactocerebroside. Our results suggest that nestin expression is a marker of pre‐O2A cells that is maintained in proliferating glial progenitors, but is quickly down‐regulated in postmitotic oligodendrocytes (A007+/galacto‐cerebroside+) along with A2B5 and vimentin. However, other glial cells including type 2 astrocytes and some amoeboid microglia also share nestin expression. Microsc. Res. Tech. 52:753–765, 2001. © 2001 Wiley‐Liss, Inc.

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