Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/26148
Title: Amyloid beta-peptide 31-35-induced neuronal apoptosis is mediated by caspase-dependent pathways via cAMP-dependent protein kinase A activation
Authors: Zhao, L
Qian, ZM
Zhang, C
Yung, WH
Fang, D
Ke, Y
Keywords: Amyloid beta-peptide 31-35 (A beta[31-35])
Apoptosis
Cortical neurons
Group III metabotropic glutamate receptors (mGluRs)
Neuroprotection
Caspase-dependent intrinsic and extrinsic pathways
PKA-dependent pathway
Issue Date: 2008
Publisher: Blackwell Publishing
Source: Aging cell, 2008, v. 7, no. 1, p. 47-57 How to cite?
Journal: Aging Cell 
Abstract: This study aims to investigate the roles of the protein kinase A (PKA)- and caspase-dependent pathways in amyloid beta-peptide 31-35 (A beta[31-35])-induced apoptosis, and the mechanisms of neuroprotection by group III metabotropic glutamate receptor (mGluR) activation against apoptosis induced by A beta[31-35] in cortical neurons. We demonstrated that A beta[31-35] induces neuronal apoptosis as well as a significant increase in caspase-3, -8 and -9. Activation of group III mGluRs by L-serine-O-phosphate and (R,S)-4-phosphonophenylglycine (two group III mGluR agonists), which attenuate the effects of A beta[31-35], provides neuroprotection to the cortical neurons subjected to A beta[31-35]. We also showed that Rp-cAMP, an inhibitor of cAMP-dependent PKA, has the ability to protect neurons from A beta[31-35]-induced apoptosis and to reverse almost completely the effects of A beta[31-35] on the activities of caspase-3. Further, we found that Sp-cAMP, an activator of cAMP-dependent PKA, can significantly abolish the L-serine-O-phosphate- and (R,S)-4-phosphonophenylglycine-induced neuroprotection against apoptosis, and decrease caspase-3, -8 and -9 in the A beta[31-35]-treated neurons. Our findings suggest that neuronal apoptosis induced by A beta[31-35] is mediated by the PKA-dependent pathway as well as the caspase-dependent intrinsic and extrinsic apoptotic pathways. Activation of group III mGluRs protects neurons from A beta[31-35]-induced apoptosis by blocking the caspase-dependent pathways. Inhibition of the PKA-dependent pathway might also protect neurons from A beta[31-35]-induced apoptosis by blocking the caspase-dependent pathways. Taken together, our observations suggest that A beta[31-35] might have the ability to activate PKA, which in turn activates the caspase-dependent intrinsic and extrinsic apoptotic pathways, inducing apoptosis in the cortical neurons.
URI: http://hdl.handle.net/10397/26148
ISSN: 1474-9718
DOI: 10.1111/j.1474-9726.2007.00352.x
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