0000000000068864

AUTHOR

Christina Esdar

Retinoic Acid Induces Apoptosis-Associated Neural Differentiation of a Murine Teratocarcinoma Cell Line

Abstract: Incubation with all-trans retinoic acid (RA) induces PCC7-Mz1 embryonic carcinoma cells to cease proliferation and to develop into a tissue-like pattern of neuronal, astroglial, and fibroblast-like derivatives over a period of several days. Concomitant with the induction of differentiation by RA, a sizable fraction of the Mz1 stem cells detaches and dies, with the maximal level of cell death achieved after 10 h of RA treatment. This RA-induced cell death fulfills all criteria of apoptosis, including nuclear condensation, intranucleosomal DNA degradation, expression of cysteine aspases (caspases), and the formation of apoptotic bodies. Apoptosis could be suppressed by the pan-caspa…

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Differentiation-associated apoptosis of neural stem cells is effected by Bcl-2 overexpression: impact on cell lineage determination

Apoptosis is an integral part of neural development. To elucidate the importance of programmed cell death on cell lineage determination we utilized murine PCC7-Mzl cells, a model system for neural differentiation. Treatment of pluripotent PCC7-Mzl stem cells with 0.1 microM all-trans retinoic acid (RA) causes a cease of proliferation and an initiation of differentiation into neurons, glial cells and fibroblasts. Simultaneously, a fraction of the cell culture (ca. 25%) dies within 24 h by apoptosis. We transfected PCC7-Mzl cells with the human bcl-2 cDNA and generated PCC7-Mz-Bcl-2 cell lines expressing two- to tenfold higher levels of Bcl-2 than parental cells. Overexpression of Bcl-2 resul…

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PCR Typing of Alu Elements — Molecular Genetics and Forensic Application

Alu repeats belong to the family of short interspersed elements (SINEs) and are among the most abundant repetitive DNA sequences in the mammalian genome. They represent mobile genetic elements ancestrally derived from the 7SL RNA gene and have presumably spread within the genome by retroposition (reviewed in [1]). A particular group of Alu repeats appears to be human-specific (HS subfamily) and has expanded only recently within the human genome as indicated by distinct dimorphisms at various loci due to the presence or absence of an Alu repeat. In recent extensive studies, the frequency distributions of Alu insertions at selected loci in various human racial groups and populations were dete…

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Production of ceramides causes apoptosis during early neural differentiation in vitro.

To investigate signal transduction pathways leading to apoptosis during the early phase of neurogenesis, we employed PCC7-Mz1 cells, which cease to proliferate and begin to differentiate into a stable pattern of neurons, astroglial cells, and fibroblasts upon incubation with retinoic acid (RA). As part of lineage determination, a sizable fraction of RA-treated cultures die by apoptosis. Applying natural long-chain C(16)-ceramides as well as membrane-permeable C(2)/C(6)-ceramide analogs caused apoptosis, whereas the biologically nonactive C(2)-dihydroceramide did not. Treating PCC7-Mz1 stem cells with a neutral sphingomyelinase or with the ceramidase inhibitor N-oleoylethanolamine elevated t…

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