Linked Life Data

18760331

Source:http://linkedlifedata.com/resource/pubmed/id/18760331

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-9-22
pubmed:abstractText
Accumulation and deposition of amyloid beta peptide (Abeta) in the brain causes neuronal apoptosis and eventually leads to Alzheimer's disease (AD). A therapeutic target for AD is to block the cascade reaction induced by Abeta. It has been demonstrated that glucagon-like peptide-1 (GLP-1), which is an endogenous insulinotropic peptide secreted from the gut, binds to its receptor in the brain and possesses neuroprotective effects. Using site-directed mutagenesis and gene recombination techniques, we generated a mutated recombinant human glucagon-like peptide-1 (mGLP-1) which has longer half-life as compared with native GLP-1. This present work aims to examine whether mGLP-1 attenuates Abeta(1-42)-mediated cytotoxicity in SH-SY5Y cells and to explore the possible mechanisms. Our data indicate that > or = 0.02 ng/ml of mGLP-1 facilitated cell proliferation and 0.1 ng/ml and 0.5 ng/ml of mGLP-1 rescued SH-SY5Y cells from Abeta(1-42)-induced apoptosis. Moreover, Abeta(1-42) treatment dramatically stimulated the release of Ca(2+) from internal calcium stores in SH-SY5Y cells, while mGLP-1 helped to maintain the intracellular Ca(2+) homeostasis. Abeta(1-42) also significantly increased the expression level of TP53 and Bax genes which are involved in apoptotic pathways, and mGLP-1 decreased Abeta(1-42)-induced up-regulation of TP53 and Bax. Since mGLP-1 treatment elevated cytosolic cAMP concentration in SH-SY5Y cells, we postulate that mGLP-1 may exert its influence via binding to GLP-1 receptors in SH-SY5Y cells and stimulating the production of cAMP. These results suggest that mGLP-1 exhibited neuronal protection properties, and could potentially be a novel therapeutic agent for intervention in Alzheimer's disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0304-3940
pubmed:author
pubmed:issnType
Print
pubmed:day
31
pubmed:volume
444
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
217-21
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Mutated recombinant human glucagon-like peptide-1 protects SH-SY5Y cells from apoptosis induced by amyloid-beta peptide (1-42).
pubmed:affiliation
Shanghai Institute of Brain Functional Genomics, and Key Laboratory of Brain Functional Genomics, MOE & STCSM, East China Normal University, No. 3663 North Zhongshan Road, Shanghai 200062, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't