Linked Life Data

7240242

Source:http://linkedlifedata.com/resource/pubmed/id/7240242

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
1981-8-27
pubmed:abstractText
ML236B is a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) (EC 1.1.1.34), the major regulatory enzyme in cholesterol biosynthesis. This compound inhibits cell growth when present in the culture medium of CHO-K1 cells at a concentration as low as 0.1 micrograms/ml. Addition of the product of the HMG-CoA reductase reaction, mevalonate, to the culture medium prevents the cytotoxic effects of ML236B at a concentration of inhibitor as high as 50 micrograms/ml. Using a stepwise selection procedure, we have obtained two variant cell lines which are resistant to the presence of 8 micrograms/ml of ML236B in the culture medium. The rates of cholesterol synthesis and the cholesterol levels in the variant cell lines, grown in the presence of ML236B, are similar to those of the parental CHO-K1 cell line grown in the absence of inhibitor. Assays of HMG-CoA reductase activity from extracts of variant cells, grown in the presence of inhibitor, reveal that the variant cell lines have an approximately 40-fold higher HMG-CoA reductase activity than does the parental CHO-K1 cell line grown in the absence of inhibitor. However, when the variant cell lines are grown without ML236B in the culture medium, the HMG-CoA reductase activity returns to the parental CHO-K1 level within 5 days, but the resistant phenotype is stable for up to 9 months. We conclude that the variant cell lines are unable to overcome the cytotoxic effects of ML236B by a mechanism which leads to overaccumulation of HMG-CoA reductase which in turn permits normal mevalonate metabolism and cholesterol synthesis to take place.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
256
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6762-8
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1981
pubmed:articleTitle
Isolation and characterization of cells resistant to ML236B (compactin) with increased levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.