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p53‐Mediated Activities in NS ‐5 Neural Stem Cells: Effects of Ethanol
Author(s) -
Miller Michael W.
Publication year - 2019
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.13976
Subject(s) - biology , apoptosis , dna damage , neural stem cell , transforming growth factor , cell cycle , microbiology and biotechnology , growth factor , cell growth , dna repair , transfection , cancer research , stem cell , cell culture , dna , genetics , receptor
Background Transforming growth factor ( TGF ) β1 and ethanol (EtOH) powerfully inhibit the proliferation, DNA repair, and survival of neural stem cells ( NSC s). The present study tests the hypothesis that the EtOH‐induced DNA damage response is mediated through p53 pathways and influenced by growth factor signals. Methods Cultures of nonimmortalized NSC s, NS ‐5 cells, were transfected with p53 si RNA , exposed to either the mitogenic fibroblast growth factor ( FGF ) 2 or antimitogenic TGF β1, and to EtOH. Stage‐specific cellular and genomic responses were examined. Results p53 status, EtOH exposure, and growth factor significantly affected the expression of transcripts related to the DNA damage response (including those coding for excision repair proteins), mitotic promoters, and regulators of cell death via the tumor necrosis factor pathway. There were significant compensatory increases in p53 family members, p63 and p73, notably in regard to the regulation of cell cycle restriction and apoptosis. Treatment with p53 si RNA potentiated EtOH‐ and TGF β1‐induced changes in the numbers of proliferating NSC s and increased the proportion of NSC s expressing the apoptotic marker annexin V. Conclusions Thus, it appears that EtOH and TGF β1 affect proliferation, DNA repair, and survival of NSC s via p53‐mediated activities.