Linked Life Data

9924181

Source:http://linkedlifedata.com/resource/pubmed/id/9924181

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1999-3-30
pubmed:abstractText
Streptozotocin (STZ) is believed to induce pancreatic beta cell death in mice by depleting the cell of NAD+NADH. The drug is known to cause a greater depletion of beta cell NAD+NADH in C57bl/6J mice than in Balb/c mice. To investigate the basis for this strain difference, we compared the effects of streptozotocin on poly(ADP-ribose)polymerase (PARP) activation - the major site of NAD consumption, and on mitochondrial activity - the major site of NAD production.%A significant strain difference was demonstrated in STZ-induced PARP activation (fmol NAD incorporated/min/microgram DNA+/-s.e.m.: Balb/c control 2.28+/-0.14, Balb STZ 3.11+/-0.25; C57bl/6J control 2.57+/-0.29, C57bl/6J STZ 4.17+/-0.24). In comparison, no strain difference could be demonstrated in hydrogen-peroxide-induced PARP activation. No strain differences could be detected in the activity of STZ-treated islet mitochondria as measured by determining ATP production (pmol/microgram protein/h+/-s. e.m.: Balb/c control 0.20+/-0.02, Balb/c STZ 0.15+/-0.02; C57bl/6J control 0.23+/- 0.03, C57bl/6J STZ 0.15+/-0.02) or by 3-[4, 5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) dye reduction (change in optical density/mg protein+/-s.e.m.: Balb/c control 10.19+/-0.62, Balb/c STZ 6.01+/-1.17; C57bl/6J control 6. 15+/-0.98, C57bl/6J STZ 5.81+/-0.96).% The strain difference in STZ-induced NAD depletion appears to be due to a difference in NAD consumption and not a difference in a mitochondrial process involved in replacing decreasing NAD concentrations. It is unlikely that a strain difference in the enzymic activity of PARP is responsible for strain differences in the effects of STZ, as no strain differences in hydrogen-peroxide-induced PARP activation could be detected. Thus the greater PARP activation, NAD depletion and beta cell death observed in C57bl/6J islets may be due to greater levels of DNA damage or differences in the DNA excision repair processes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0952-5041
pubmed:author
pubmed:issnType
Print
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
65-70
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:9924181-Adenosine Triphosphate, pubmed-meshheading:9924181-Animals, pubmed-meshheading:9924181-DNA Damage, pubmed-meshheading:9924181-DNA Repair, pubmed-meshheading:9924181-Diabetes Mellitus, Experimental, pubmed-meshheading:9924181-Disease Susceptibility, pubmed-meshheading:9924181-Drug Resistance, pubmed-meshheading:9924181-Enzyme Activation, pubmed-meshheading:9924181-Hydrogen Peroxide, pubmed-meshheading:9924181-Islets of Langerhans, pubmed-meshheading:9924181-Male, pubmed-meshheading:9924181-Mice, pubmed-meshheading:9924181-Mice, Inbred BALB C, pubmed-meshheading:9924181-Mice, Inbred C57BL, pubmed-meshheading:9924181-Mitochondria, pubmed-meshheading:9924181-NAD, pubmed-meshheading:9924181-Poly(ADP-ribose) Polymerases, pubmed-meshheading:9924181-Species Specificity, pubmed-meshheading:9924181-Streptozocin
pubmed:year
1999
pubmed:articleTitle
Poly(ADP-ribose)polymerase activation determines strain sensitivity to streptozotocin-induced beta cell death in inbred mice.
pubmed:affiliation
Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Brisbane, 4102, Australia.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't