Linked Life Data

14966800

Source:http://linkedlifedata.com/resource/pubmed/id/14966800

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2004-2-17
pubmed:abstractText
A balance between proliferation and cell death is critical for achieving desirable high cell densities in mammalian cell culture. In this study, we evaluate a recently discovered anti-apoptotic gene, aven, and examine its effectiveness alone and in combination with a member of the Bcl-2 family, bcl-xL. The commercially popular cell line, Chinese hamster ovary (CHO), was genetically modified to constitutively express aven, bcl-xL, and the two genes in combination. Cells were exposed to several model insults that simulate severe bioreactor environments, including serum deprivation, spent medium, and Sindbis virus infection, as well as staurosporine, a known chemical inducer of apoptosis. CHO cells exhibited DNA fragmentation, a hallmark of apoptosis, after exposure to these model insults. After exposure to serum deprivation, 4- and 5-day spent medium, and staurosporine, cells expressing Aven provided limited protection against cell death when compared with the protection afforded by cells expressing Bcl-xL alone. However, the highest survival levels for all insults were achieved when Aven was expressed in combination with Bcl-xL. In fact, Aven appeared to act synergistically to enhance the protective function of Bcl-xL for several insults, because the protective function of the two genes expressed together in one cell line often exceeded the additive protective levels of each anti-apoptosis gene expressed alone. Surprisingly, Aven expression provided a mildly pro-apoptotic response in CHO isolates infected with Sindbis virus. However, CHO cells expressing both Bcl-xL and Aven showed protection against Sindbis virus infection due to the inhibitory properties of the bcl-xL anti-apoptosis gene. This study shows that combinatorial anti-apoptosis cell engineering strategies may be the most effective mechanisms for providing extended protection against cell death in mammalian cell culture.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-3592
pubmed:author
pubmed:copyrightInfo
Copyright 2004 Wiley Periodicals, Inc.
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
85
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
589-600
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:14966800-Adaptor Proteins, Signal Transducing, pubmed-meshheading:14966800-Alphavirus Infections, pubmed-meshheading:14966800-Animals, pubmed-meshheading:14966800-Apoptosis, pubmed-meshheading:14966800-Apoptosis Regulatory Proteins, pubmed-meshheading:14966800-Bioreactors, pubmed-meshheading:14966800-CHO Cells, pubmed-meshheading:14966800-Carrier Proteins, pubmed-meshheading:14966800-Cell Culture Techniques, pubmed-meshheading:14966800-Cell Survival, pubmed-meshheading:14966800-Cricetinae, pubmed-meshheading:14966800-Cricetulus, pubmed-meshheading:14966800-Culture Media, Serum-Free, pubmed-meshheading:14966800-Cytoprotection, pubmed-meshheading:14966800-Mammals, pubmed-meshheading:14966800-Membrane Proteins, pubmed-meshheading:14966800-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:14966800-Recombinant Proteins, pubmed-meshheading:14966800-Sindbis Virus, pubmed-meshheading:14966800-Staurosporine, pubmed-meshheading:14966800-bcl-X Protein
pubmed:year
2004
pubmed:articleTitle
Aven and Bcl-xL enhance protection against apoptosis for mammalian cells exposed to various culture conditions.
pubmed:affiliation
Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, Non-P.H.S.