Carbachol blocks beta-amyloid fragment 31-35-induced apoptosis in cultured cortical neurons.
We reported previously that many neurodegenerative changes characteristic of apoptosis could be induced by a short fragment of beta-amyloid protein, A(beta31-35), in cultured newborn mice cortical neurons, and that these changes were accompanied with alterations in expression of some genes. This study was designed to examine whether the apoptotic processes and related gene modulations in this model could be affected by coadministration of carbachol by electrophoretic analysis for DNA ladder formation and by RT-PCR assays for genomic modulation. The results showed that (1) simultaneous incubation with carbachol dose- and time-dependently blocked the specific DNA ladder formation induced by exposure to A(beta31-35) and (2) the A(beta31-35)-induced downregulation of bcl-2 and upregulations of bax, p53, and c-fos genes were reversed or ameliorated by the coadministration of carbachol. It is proposed that A(beta31-35)-induced apoptosis can be prevented by carbachol through mechanisms that modulate the expression of related genes.
Yan
X
X
Department of Neurobiology, Shanxi Medical University, Taiyuan, China.
Xiao
R
R
Dou
Y
Y
Wang
S
S
Qiao
Z
Z
Qiao
J
J
D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D002217:Carbachol / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D018679:Cholinergic Agonists / Q000494:pharmacology*; D004586:Electrophoresis; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology; D009498:Neurotoxins / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016229:Amyloid beta-Peptides; D018679:Cholinergic Agonists; D018696:Neuroprotective Agents; D009498:Neurotoxins; D010446:Peptide Fragments; D002217:Carbachol