Linked Life Data

19357238

Source:http://linkedlifedata.com/resource/pubmed/id/19357238

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2009-5-29
pubmed:abstractText
Recent evidence indicates that 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP), a marker enzyme of myelin and oligodendrocytes, is also present in neural and nonneural mitochondria. However, its role in mitochondria is still completely unclear. We found CNP in rat brain mitochondria and studied the effects of CNP substrates, 2',3'-cyclic nucleotides, on functional parameters of rat brain mitochondria. 2',3'-cAMP and 2',3'-cNADP stimulated Ca(2+) overload-induced Ca(2+) release from mitochondrial matrix. This Ca(2+) release under threshold Ca(2+) load correlated with membrane potential dissipation and mitochondrial swelling. The effects of 2',3'-cyclic nucleotides were suppressed by cyclosporin A, a potent inhibitor of permeability transition (PT). PT development is a key stage in initiation of apoptotic mitochondria-induced cell death. 2',3'-cAMP effects were observed on the functions of rat brain mitochondria only when PT was developed. This demonstrates involvement of 2',3'-cAMP in PT regulation in rat brain mitochondria. We also discovered that, under PT development, the specific enzymatic activity of CNP was reduced. Thus we hypothesize that suppression of CNP activity under threshold Ca(2+) load leads to elevation of 2',3'-cAMP levels that, in turn, promote PT development in rat brain mitochondria. Similar effects of 2',3'-cyclic nucleotides were observed in rat liver mitochondria. Involvement of CNP in PT regulation was confirmed in experiments using mitochondria from CNP-knockdown oligodendrocytes (OLN93 cells). CNP reduction in these mitochondria correlated with lowering the threshold for Ca(2+) overload-induced Ca(2+) release. Thus our results reveal a new function for CNP and 2',3'-cAMP in mitochondria, being a regulator/promotor of mitochondrial PT.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0363-6143
pubmed:author
pubmed:issnType
Print
pubmed:volume
296
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
C1428-39
pubmed:meshHeading
pubmed-meshheading:19357238-2',3'-Cyclic-Nucleotide Phosphodiesterases, pubmed-meshheading:19357238-Adenine Nucleotides, pubmed-meshheading:19357238-Animals, pubmed-meshheading:19357238-Brain, pubmed-meshheading:19357238-Calcium Signaling, pubmed-meshheading:19357238-Cell Line, pubmed-meshheading:19357238-Cyclosporine, pubmed-meshheading:19357238-Male, pubmed-meshheading:19357238-Membrane Potential, Mitochondrial, pubmed-meshheading:19357238-Mitochondria, pubmed-meshheading:19357238-Mitochondria, Liver, pubmed-meshheading:19357238-Mitochondrial Membrane Transport Proteins, pubmed-meshheading:19357238-Mitochondrial Swelling, pubmed-meshheading:19357238-NADP, pubmed-meshheading:19357238-Oligodendroglia, pubmed-meshheading:19357238-RNA, Small Interfering, pubmed-meshheading:19357238-RNA Interference, pubmed-meshheading:19357238-Rats, pubmed-meshheading:19357238-Rats, Wistar, pubmed-meshheading:19357238-Time Factors
pubmed:year
2009
pubmed:articleTitle
Ca2+-dependent permeability transition regulation in rat brain mitochondria by 2',3'-cyclic nucleotides and 2',3'-cyclic nucleotide 3'-phosphodiesterase.
pubmed:affiliation
Institut für Neurobiochemie, Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, 39120 Magdeburg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't