Linked Life Data

11966440

Source:http://linkedlifedata.com/resource/pubmed/id/11966440

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2002-4-22
pubmed:abstractText
Benzamide riboside (BR) after anabolism to an analogue of NAD, was shown to inhibit the activity of NAD-dependent enzymes such as inosine 5'-monophosphate dehydrogenase (IMPDH), the rate limiting enzyme in de novo guanylate biosynthesis, and malate dehydrogenase which is involved in the citric cycle and respiratory chain. BR exhibits strong anti-carcinogenic effects due to growth retardation and due to induction of apoptosis and necrosis. Apoptosis is ascribed to the inhibition of IMPDH because cell death can be blocked by restoring intracellular guanylate metabolism by the addition of guanosine. It is shown here, however, that also survival-relevant genes such as cdc25A, akt, bcl-2 and transferrin receptor become repressed by BR, whereas the expression level of the apoptosis enforcing gene c-myc persists. Even though BR-mediated growth retardation still allows BR to induce apoptosis, rapamycin-mediated cell cycle block and cell contact inhibition prevent cell death, it strongly suggests that BR induces a type of c-Myc-dependent apoptosis. At high concentrations BR induces DNA double strand breaks by yet to be determined mechanisms that occur hours before necrosis can be detected. This is accompanied by a dramatic decrease of intracellular ATP. The artificial restoration of ATP by addition of adenosine or sufficient provision of an energy source such as glucose prevents BR-promoted necrosis and favors apoptosis. This observation may be of clinical relevance.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0929-8673
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
765-71
pubmed:dateRevised
2007-2-12
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Potential mechanisms of benzamide riboside mediated cell death.
pubmed:affiliation
Institute of Clinical Pathology, University of Vienna, Austria.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't