Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
25
pubmed:dateCreated
2006-6-21
pubmed:abstractText
Poly(ADP-ribose) polymerase-1 (PARP-1), when activated by DNA damage, promotes both cell death and inflammation. Here we report that PARP-1 enzymatic activity is directly inhibited by minocycline and other tetracycline derivatives that have previously been shown to have neuroprotective and anti-inflammatory actions. These agents were evaluated by using cortical neuron cultures in which PARP-1 activation was induced by the genotoxic agents N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or 3-morpholinosydnonimine (SIN-1). In both conditions, neuronal death was reduced by >80% either by 10 muM 3,4-dihydro-5-[4-(1-piperidinyl)butoxy]-1(2H)-isoquinolinone, an established PARP inhibitor, or by 100 nM minocycline. Neuronal NAD(+) depletion and poly(ADP-ribose) formation, which are biochemical markers of PARP-1 activation, were also blocked by 100 nM minocycline. A direct, competitive inhibition of PARP-1 by minocycline (K(i) = 13.8 +/- 1.5 nM) was confirmed by using recombinant PARP-1 in a cell-free assay. Comparison of several tetracycline derivatives showed a strong correlation (r(2) = 0.87) between potency as a PARP-1 inhibitor and potency as a neuroprotective agent during MNNG incubations, with the rank order of potency being minocycline > doxycycline > demeclocycline > chlortetracycline. These compounds are known to have other actions that could contribute their neuroprotective effects, but at far higher concentrations than shown here to inhibit PARP-1. The neuroprotective and antiinflammatory effects of minocycline and other tetracycline derivatives may be attributable to PARP-1 inhibition in some settings.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-10449410, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-10455009, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-10494847, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-10557349, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-10570184, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-10677544, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-10888929, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-11050121, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-11306611, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-11390507, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-11579149, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-11593040, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-11724929, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-11781564, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-11854472, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-11880505, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-11986668, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-12006805, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-12114629, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-12142562, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-12223530, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-12675907, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-12809599, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-12930891, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-1310595, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-14559156, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-14960594, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-15004018, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-15569265, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-15699164, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-15862784, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-15874975, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-15959554, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-15964487, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-16033424, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-16091365, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-16336636, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-1903948, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-2884353, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-6282854, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-8080500, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-8161194, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-8700830, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-9202315, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-9334719, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-9390645, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769901-9861045
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0027-8424
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
103
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9685-90
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Minocycline inhibits poly(ADP-ribose) polymerase-1 at nanomolar concentrations.
pubmed:affiliation
Department of Neurology, University of California-San Francisco and Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA 94121, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural