Linked Life Data

20010851

Source:http://linkedlifedata.com/resource/pubmed/id/20010851

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-2-1
pubmed:abstractText
Increasing evidence suggests that apoptosis may be the mechanism underlying cell death in selective loss of nigral dopaminergic neurons in Parkinson's disease (PD). Previous studies strongly suggested that c-Jun N-terminal kinase (JNK) signaling pathway has a critical role in the animal model with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. In this study, we report the inhibitory effect of a peptide designated as Tat-JBD on JNKs activation. The sequence of Tat is corresponding to the cell-membrane transduction domain of human immunodeficiency virus-type 1 (HIV-1) and the sequence of an 11-amino acid peptide is corresponding to the residues of JNK-binding domain (JBD) on JNK-interacting protein-1 (JIP-1). Tat-JBD is confirmed to perturb the assembly of JIP-1-JNKs complex, inhibit the activation of JNKs induced by MPTP and consequently diminish the phosphorylation of c-Jun. It also inhibits the phosphorylation of Bcl-2 and the releasing of Bax from Bcl-2/Bax dimmers, sequentially attenuates the translocation of Bax to mitochondria, the release of cytochrome c, the activation of caspase3 and the hydrolyzation of poly-ADP-ribose-polymerase. The death of dopaminergic neurons and the loss of dopaminergic axon in the striatum were significantly suppressed by infusion of the peptide Tat-JBD in MPTP-treated mice. Our findings imply that Tat-JBD offers neuroprotection against MPTP injury via inhibiting the JNK-signaling pathway, and may provide a promising therapeutic approach for PD.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1530-0307
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
90
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
156-67
pubmed:meshHeading
pubmed-meshheading:20010851-1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, pubmed-meshheading:20010851-Adaptor Proteins, Signal Transducing, pubmed-meshheading:20010851-Animals, pubmed-meshheading:20010851-Apoptosis, pubmed-meshheading:20010851-Disease Models, Animal, pubmed-meshheading:20010851-In Situ Nick-End Labeling, pubmed-meshheading:20010851-JNK Mitogen-Activated Protein Kinases, pubmed-meshheading:20010851-Male, pubmed-meshheading:20010851-Mice, pubmed-meshheading:20010851-Nerve Degeneration, pubmed-meshheading:20010851-Neuroprotective Agents, pubmed-meshheading:20010851-Parkinson Disease, pubmed-meshheading:20010851-Peptides, pubmed-meshheading:20010851-Phosphorylation, pubmed-meshheading:20010851-Protein Kinase Inhibitors, pubmed-meshheading:20010851-tat Gene Products, Human Immunodeficiency Virus
pubmed:year
2010
pubmed:articleTitle
Small peptide inhibitor of JNKs protects against MPTP-induced nigral dopaminergic injury via inhibiting the JNK-signaling pathway.
pubmed:affiliation
Institute of Health Science, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) & Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't